Anti-transthyretin antibody, compositions comprising said antibody and methods for treating or preventing transthyretin-mediated amyloidosis

Abstract

Provided herein are anti-transthyretin (TTR) antibodies, corresponding polynucleotides and expression vectors as well as compositions (e.g., pharmaceutical compositions) and related articles of manufacture that contain the anti-TTR antibody as a drug. Provided herein are also methods of treating or preventing transthyretin-mediated amyloidosis (ATTR) in a subject in need thereof using the pharmaceutical compositions. Additionally, provided herein are methods for validating, identifying, and screening of an amyloid depleting drug using high-resolution live-cell imaging as well as methods for producing a pharmaceutical composition of an amyloid depleting drug and kits suitable for use in said methods.

Description

[0001]New PCT applicationApplicants: Neurimmune AG and Alexion Pharmaceuticals, Inc.WJS Ref.: NE30A106 / P-WO / WO ANTI-TRANSTHYRETIN ANTIBODY, COMPOSITIONS COMPRISING SAID ANTIBODY AND METHODS FOR TREATING OR PREVENTING TRANSTHYRETIN-MEDIATED AMYLOIDOSIS Technical FieldThis present disclosure relates to anti-transthyretin (TTR) antibodies, correspondingpolynucleotides and expression vectors, as well as to compositions comprising said antibodiesand methods of treating or preventing transthyretin-mediated amyloidosis (ATTR). The presentdisclosure further relates to methods for validating, identifying, and screening of amyloiddepleting drugs using high-resolution live-cell imaging as well as to methods for producing apharmaceutical composition of an amyloid depleting drug and kits suitable for use in said methods. Background Transthyretin (TTR) is a soluble protein involved in thyroxin and retinol transport in the body. TTR is secreted in the blood by the liver and in the cerebrospinal fluid by the choroid plexus and is also expressed in specific tissues like the pancreatic alpha cells or retinal epithelium. Under specific conditions which have been poorly elucidated and may include acidic pH, oxidative stress and local factors, the TTR protein adopts misfolded, misassembled and / or aggregated TTR conformations and becomes toxic, which can lead to transthyretin-mediated amyloidosis (ATTR). There exists a need for antibodies and drug products for administering antibodies (e.g., humananti-TTR antibodies) that target aggregated TTR suitable for treating or preventing ATTR in asubject. SummaryProvided herein is, inter alia, an anti-transthyretin (TTR) antibody, correspondingpolynucleotides and expression vectors as well as compositions (e.g., pharmaceuticalcompositions) and related articles of manufacture that contain the anti-TTR antibody as a drug.Additionally, provided herein are, inter alia, methods of treating or preventing transthyretin-mediated amyloidosis (ATTR) in a subject in need thereof using the pharmaceuticalcompositions. In accordance with the present disclosure, a human anti-TTR antibody, which is specific for the disease associated amyloidogenic form of TTR, featuring ALXN2220, also known as NI006 and which has been assigned the CAS Registry Number 2965214-50-8, has been manufactured,i.e., by recombinantly expressing the antibody’s heavy chain (HC) and light chain (LC) in theChinese Ovary Hamster (CHO) K1 cell line, which recombinant antibody possesses a uniquepattern of posttranslational modifications (PTMs) and in particular a unique glycosylationprofile; see Examples 1 to 3.Antibody NI006 / ALXN2220 is a fully human IgG1m3 allotype antibody and comprises thehuman constant heavy chain (HC) amino acid sequence as set forth in SEQ ID NO: 7, 9, and39, respectively, and a corresponding human constant light chain (LC), here kappa light chain,as set forth in SEQ ID NO: 8. As explained further below, the NI006 / ALXN2220 IgG1antibodies are made up as tetramers consisting of HC and two light LC chains linked bydisulfide bridges. Furthermore, the closest human gene / allele of the variable domains areIGKV1-3901 (93.3%) + IGKJ101 (100%) and IGHV4-30-201 (89.5%) + IGHJ302 (100%). The antibody CDRs (e.g., variable heavy (VH) and / or variable light (VL) chain CDRs comprising VHCDRs1-3 and VLCDRs1-3, including variable heavy and light chain domains) of NI006 / ALXN2220 has been first described in WO 2015 / 092077 A1 (designated as antibody NI-301.37F1) and in Michalon et al., Nat. Commun.12 (2021), 3142 (designated as antibodyNI301A), the disclosure in these documents being incorporated by reference herein in partspertinent thereto. Described herein are complete (e.g., full-length) variable heavy chain (VH) and light chain (VL) of the NI006 / ALXN2220 antibody including its heavy chain and / or light chain constant regions. The present disclosure further provides full-length NI006 / ALXN2220 antibody comprising PTMs in its heavy chain and / or light chain, which antibody is particularlysuitable for providing a stable formulation that can be used as pharmaceutical composition inthe treatment of ATTR. In particular, the antibodies of the present disclosure comprise modified glutamine at N- terminal of the heavy chain sequence, wherein the modification comprises a pyro-glutamic acid(abundance in sample, e.g., recombinant formulation of the antibody about 99.9% or more, e.g., 100%). In further embodiments, the antibodies of the present disclosure comprise a clipped C-terminal lysine in the heavy chain (abundance in sample, e.g., recombinant formulation of theantibody, of about 95.8% or more, e.g., 96%, 97%, 98%, 99% or even 100%).NI006 / ALXN2220 antibody subtype containing both the N-terminal pyroglutamate and C-terminal lysine deletion have been identified as the major post-translational modifications viaanalysis of the antibody heavy chain sequence. An N-terminal pyroglutamate modification is beneficial in therapeutic antibodies by enhancing stability, consistency, and reducing immunogenicity. In particular, the N-terminal pyroglutamate modification helps protect the antibody’s N-terminus from proteolytic degradation by enzymes which increases its stability and extends the half-life of the antibody in circulation. Furthermore, pyroglutamate formation enhances the homogeneity of the antibody preparation by ensuring a consistent N-terminal structure across molecules. This consistency can be beneficial for quality control and regulatory approval, as it results in a more uniform product with predictable properties. Moreover, it helps reduce the risk of immunogenicity. By cleaving the N-terminal glutamine or glutamic acid, it prevents unwanted immune responses that might be triggered by unmodified N-terminal residues, which could otherwise be recognized as foreign. The enzyme responsible for converting N-terminal glutamine (or sometimes glutamic acid) into pyroglutamate is called glutaminyl cyclase. The activity level of this enzyme can vary across cell types and can significantly influence the extent of pyroglutamate formation. C-terminal lysine clipping is advantageous as it enhances charge homogeneity, reduces immunogenicity, improves consistency, and does not impact the antibody’s functionality. In particular, the presence of C-terminal lysine adds a positive charge to the antibody, which can introduce charge heterogeneity across the antibody population. By clipping the C-terminal lysine, the antibody preparation becomes more uniform in charge, simplifying downstream processes like purification and improving batch-to-batch consistency and homogeneity, which is beneficial for quality control. Furthermore, antibodies naturally lack the C-terminal lysine due to proteolytic removal in vivo. Leaving the lysine on can make the antibody appear foreign to the immune system, potentially triggering an immune response. Removing this lysine reduces the risk of immunogenicity, making the therapeutic antibody more biocompatible. The C-terminal lysine residue does not play a role in the antibody’s binding to its target antigen or its interaction with Fc receptors and thus, its removal does not impact the antibody’s therapeutic activity, so clipping it is beneficial without compromising efficacy. The efficiency of C- terminal lysine clipping can depend on the cell line used for antibody production as different cell lines vary in their protease activity and the efficiency with which they remove C-terminal lysine residues from antibodies. Accordingly, an antibody having an N-terminal pyroglutamate modification and C-terminal lysine clipping is beneficial for therapeutic purposes and thus, is a preferred embodiment of the present invention.Furthermore, additional modifications, such as methionine oxidation, asparagine deamidationand asparagine succinimide formation, have been experimentally determined, as shown inTable 3. Accordingly, the present disclosure relates to a mature anti-TTR antibody whichcomprises a HC having the amino acid sequence of SEQ ID NO: 7, wherein X1is absent, glutamine, or a pyroglutamate (pE); X2 is methionine or oxidized methionine; X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine or deamidated asparagine; X5 is proline or amidated proline; X6 is absent or glycine; and X7is absent or lysine, and a LC having the amino acid sequence of SEQ ID NO: 8.Accordingly, in one embodiment, the antibody of the present disclosure comprises a HC havingthe amino acid sequence of SEQ ID NO: 7, wherein the N-terminal glutamine (Q1), in SEQ IDNO: 7, denoted by X1, is absent or is present, preferably absent. In embodiments, X1 is presentas glutamine, or as pyroglutamate (pE); preferably X1 is pE.In addition, or alternatively, the antibody of the present disclosure comprises a HC having theamino acid sequence of SEQ ID NO: 7, wherein the C-terminal lysine (K450), in SEQ ID NO:7, denoted by X7, is absent or is present. In preferred embodiments, X7is absent.In one embodiment, the antibody of the present disclosure comprises an HC having the aminoacid sequence of SEQ ID NO: 39, wherein N-terminal residue X1is absent or present as aglutamine or a pE. In embodiments, X2 is a methionine or an oxidized methionine. In embodiments, X3is an asparagine, a deamidated asparagine, or an asparagine comprising a succinimide. In embodiments, X4 is an asparagine, a deamidated asparagine, or an asparagine comprising a succinimide. In embodiments, X5 is a proline or an amidated proline. In embodiments, X6is absent or a glycine. In embodiments, X7is absent or a lysine. In embodiments, XI is an asparagine or a deamidated asparagine. In embodiments, XII is a methionine or an oxidized methionine. In embodiments, XIII is a methionine or an oxidized methionine. In embodiments, XIVis an aspartate or an iso-aspartate. In embodiments, XVis an asparagine or a glycosylated asparagine. In embodiments, XVI is a methionine or an oxidizedmethionine. In embodiments, XVII is a methionine or an oxidized methionine. In embodiments,the antibody comprises an LC having the amino acid sequence of SEQ ID NO: 8. In embodiments, the antibody of the present disclosure comprises an HC having the amino acidsequence of SEQ ID NO: 7 and 39, respectively. In some embodiments, X1 is a pE. In someembodiments, X6is absent. In some embodiments, X7is absent. In some embodiments, X5isamidated. In some embodiments, X2 is an oxidized methionine. In some embodiments, X3 is adeamidated asparagine. In other embodiments, X3 is an asparagine comprising a succinimide. In some embodiments, X4is deamidated asparagine. In some embodiments, XI is a deamidated asparagine. In some embodiments, XII is an oxidized methionine. In some embodiments, XIIIis an oxidized methionine. In some embodiments, XIVis an iso-aspartate. In some embodiments, XVis a glycosylated asparagine. In someembodiments, XVI is an oxidized methionine. In some embodiments, XVII is an oxidizedmethionine.In some embodiments, X1 is a pE, X2 is a methionine, X3 is an asparagine, X4 is an asparagine,X5 is a proline, X6 is a glycine, and X7 is absent.In some preferred embodiments, X1 is a pE, X2 is a methionine, X3 is an asparagine, X4 is anasparagine, X5 is a proline, X6 is a glycine, X7 is absent, XI is an asparagine, XII is a methionine,XIIIis methionine, XIVis an aspartate, XVis a glycosylated asparagine, XVIis a methionine, and XVIIis a methionine. In some embodiments, X1is a pE, X2is an oxidized methionine, X3is a deamidated asparagine or asparagine comprising a succinimide, X4 is a deamidated asparagine or an asparaginecomprising a succinimide, X5 is a proline, X6 is a glycine, and X7 is absent.In some embodiments, X1 is a pE, X2 is an oxidized methionine, X3 is a deamidated asparagine or an asparagine comprising a succinimide, X4 is a deamidated asparagine or an asparagine comprising a succinimide, X5is an amidated proline, X6is absent, and X7is absent. In some embodiments, X1 is a pE, X2 is an oxidized methionine, X3 is a deamidated asparagine or an asparagine comprising a succinimide, X4is a deamidated asparagine or an asparaginecomprising a succinimide, X5 is a proline, X6 is a glycine, X7 is absent, XI is an asparagine, XIIis a methionine, XIII is a methionine, XIV is an aspartate, XV is a glycosylated asparagine, XVI is a methionine, and XVII is a methionine.In some embodiments, X1 is a pE, X2 is an oxidized methionine, X3 is a deamidated asparagineor an asparagine comprising a succinimide, X4 is a deamidated asparagine or an asparaginecomprising a succinimide, X5 is an amidated proline, X6 is absent, X7 is absent, XI is anasparagine, XII is a methionine, XIII is a methionine, XIV is an aspartate, XV is a glycosylated asparagine, XVI is a methionine, and XVII is a methionine. In embodiments, the C-terminal lysine (C450, numbering is based on the HC polypeptidesequence which comprises the N-terminal glutamine or pyroglutamate) of the HC of theantibody of the present disclosure may be clipped off (e.g., via proteolytic cleavage).Accordingly, in embodiments, the antibody of the present disclosure comprises a HC havingthe amino acid sequence of SEQ ID NO: 7 and 39, respectively, wherein the C-terminal lysine,in SEQ ID NO: 7 and 39, respectively, denoted by X7, is either absent or present. Preferably,the C-terminal lysine at X7 of SEQ ID NO: 7 and 39, respectively is absent.In embodiments wherein the C-terminal lysine in the HC of the antibodies of the presentdisclosure is absent, the then resulting C-terminal glycine (G449, numbering is based on theHC polypeptide sequence which comprises the N-terminal glutamine or pyroglutamate) mayalso be modified. Accordingly, in embodiments, the antibody of the present disclosurecomprises a HC having the amino acid sequence of SEQ ID NO: 7 and 39, respectively, whereinthe C-terminal lysine at X7 is absent and amino acid proximal thereto at the C-terminus of SEQID NO: 7 and 39, respectively, denoted by glycine at X6, is either absent or present.In some embodiments, wherein the C-terminal lysine and glycine in the HC of the antibodiesof the present disclosure are both absent, the then resulting C-terminal proline (P448, numbering is based on the HC polypeptide sequence which comprises the N-terminal glutamineor pyroglutamate) may be amidated. Accordingly, in one embodiment, the antibody of thepresent disclosure comprises a HC having the amino acid sequence of SEQ ID NO: 7 and 39,respectively, wherein the C-terminal lysine at X7 and glycine at X6, are both absent, and theamino acid proximal thereto at the C-terminus of SEQ ID NO: 7 and 39, respectively, denotedby proline at X5, is either amidated or unmodified, preferably amidated. In addition, or alternatively, in embodiments, in the heavy chain of the antibodies of the present disclosure, the methionine at position 255 (M255, numbering is based on the HC polypeptidesequence which comprises the N-terminal glutamine or pyroglutamate) may be oxidized.Accordingly, in one embodiment, the antibody of the present disclosure comprises a HC havingthe amino acid sequence of SEQ ID NO: 7 and 39, respectively, wherein the M255, in SEQ IDNO: 7 and 39, respectively, denoted by methionine at X2, is either oxidized (modified) orunmodified. In addition, or alternatively, in embodiments, in the heavy chain of the antibodies of the present disclosure, the asparagine at position 318 (N318, numbering is based on the HC polypeptidesequence which comprises the N-terminal glutamine or pyroglutamate) may be unmodified ordeamidated or may comprise a succinimide. Accordingly, in one embodiment, the antibody ofthe present disclosure comprises a HC having the amino acid sequence of SEQ ID NO: 7 and39, respectively, wherein the N318, in SEQ ID NO: 7 and 39, respectively, denoted byasparagine at X3, is either modified or unmodified, preferably wherein the modified asparagineat X3 is deamidated (modified) or comprises a succinimide (modified).In addition, or alternatively, in embodiments, in the heavy chain of the antibodies of the present disclosure, the asparagine at position 387 (N387, numbering is based on the HC polypeptidesequence which comprises the N-terminal glutamine or pyroglutamate) may be unmodified ormodified, e.g., wherein the modified amino acid is deamidated. Accordingly, in oneembodiment, the antibody of the present disclosure comprises a HC having the amino acidsequence of SEQ ID NO: 7 and 39, respectively, wherein the N387, in SEQ ID NO: 7 and 39,respectively, denoted by asparagine at X4, is either deamidated (modified) or is unmodified.In embodiments, the antibodies of the present disclosure comprise N-glycosylation. In some embodiments, at least one amino acid in the heavy chain of the antibodies of the presentdisclosure is N-glycosylated. Data in Example 2 show that N-glycosylation is a substantial PTMof the backbone amnio acid sequence making up the antibody of the present disclosure. In thiscontext, the N-glycosylation site was identified at position Asn300 (HC N300, numbering basedon antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyrogluatmate (X1).In some preferred embodiments, the disclosure relates to an antibody comprising a heavy chainpolypeptide sequence set forth in SEQ ID NO: 7 and 39, respectively, wherein X1 ispyroglutamate and wherein X7 is cleaved off and wherein asparagine (N) in amino acid position300 is N-glycosylated.In some preferred embodiments, the disclosure relates to anti-TTR antibodies comprising a HCcomprising the sequence set forth in SEQ ID NO: 7 and 39, respectively, wherein the glutamine(X1) is modified to pyroglutamate, the lysine (X7) is absent, and in which the amino acids atpositions X2, X3, X4,X5, and X6are either modified as indicated above or unmodified, preferably unmodified, and at least one amino acid is N-glycosylated. Preferably, in such embodiments, the N-glycosylation site is at position Asn300 (N300, numbering based on antibody HCpolypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamineor pyroglutamate (X1)). In a particular embodiment, the antibodies of the present disclosure comprise a pyro-glutamic acid at the N-terminal of the heavy chain sequence instead of glutamine, wherein the abundancein sample is about 99.9% or more, e.g., 100%. In further particular embodiments, the antibodiesof the present disclosure comprise a C-terminal in which the C-terminal lysine in the heavychain is clipped off, wherein the abundance in sample is about 95.8% or more, e.g., 96%, 97%,98%, 99% or even 100%. In further particular embodiments, the antibodies of the present disclosure comprise deamidated asparagine at position 58 (N58 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments, the antibodies of the present disclosure comprise deamidated asparagine at position 318 (N318 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine orpyroglutamate (X1)), wherein the abundance in sample is about 9% or less, e.g., 8%, 7%, 6%,5%, 4%, 3%, 2%, 1% or 0%. In further particular embodiments, the antibodies of the present disclosure comprise deamidated asparagine at position 387 (N387 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments, the antibodies of the present disclosure comprise oxidized methionine at position 71 (M71 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments, the antibodies of the present disclosure comprise oxidized methionine at position 115 (M15 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments,the antibodies of the present disclosure comprise oxidized methionine at position 255 (M255based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments, the antibodies of the present disclosure comprise oxidized methionine at position 361 (M361 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. In further particular embodiments, the antibodies of the present disclosure comprise oxidized methionine at position 431 (M413 based on antibody HC polypeptide sequence of SEQ ID NO: 7 and 39, respectively having the N-terminal glutamine or pyroglutamate (X1)), wherein the abundance in sample is about 5% or less, e.g., 4%, 3%, 2%, 1%, or 0%. Furthermore, the antibody of the present disclosure may comprise a glycated heavy chain and / or a glycated light chain.As mentioned above, an antibody having an N-terminal pyroglutamate modification and C-terminal lysine clipping is beneficial for therapeutic purposes, but it is preferred that the abundance of the other mentioned PTMs is rather low. For example, methionine oxidation, iso-aspartate formation, or deamidated asparagine in therapeutic antibodies is generally notfavorable because it can negatively impact the stability, function, safety, and efficiency andthus, the abundance of methionine oxidation, iso-aspartate formation and asparaginedeamidation should preferably around or below 5%.Accordingly, in a preferred embodiment, X1 is a pE, X2 is a methionine, X3 is an asparagine,X4 is an asparagine, X5 is a proline, X6 is a glycine, X7 is absent, XI is an asparagine, XII is amethionine, XIIIis methionine, XIVis an aspartate, XVis a glycosylated asparagine, XVIis a methionine, and XVII is a methionine.In embodiments, the antibody of the present disclosure comprises two HCs, each having anamino acid sequence set forth in SEQ ID NO: 7 and 39, respectively, and two LCs, each havingan amino acid sequence set forth in SEQ ID NO: 8, and wherein the glutamine at the N-terminus(X1) of the HC sequence, in each case, independently, is modified as pyro-glutamic acid (pE).In embodiments, the antibody of the disclosure comprises two HCs comprising the amino acidsequence set forth in SEQ ID NO: 7 and 39, respectively, wherein the C-terminal lysine (X7) ofthe HC sequence, in each case, independently, is absent. In embodiments, the antibody of thedisclosure comprises two HCs comprising the amino acid sequence set forth in SEQ ID NO: 7and 39, respectively, wherein the heavy chain, in each case, independently, is N-glycosylated,preferably wherein the N-glycosylation site is at position Asn300. In embodiments, theantibody of the disclosure comprises two HCs comprising the amino acid sequence set forth inSEQ ID NO: 7, wherein the amino acids at position X2, X3, X4, and X5 of SEQ ID NO: 7 and39, respectively are either modified or unmodified, preferably unmodified.In embodiments, the antibody of the present disclosure comprises two HCs, each having anamino acid sequence set forth in SEQ ID NO: 7 and 39, respectively, and two LCs, each havingan amino acid sequence set forth in SEQ ID NO: 8, and wherein the glutamine at the N-terminus(X1) of the HC sequence, in each case, independently, is modified as pyro-glutamic acid (pE);the C-terminal lysine (X7) of the HC sequence, in each case, independently, is absent; the heavychain, in each case, independently, is N-glycosylated, preferably wherein the N-glycosylationsite is at position Asn300 of SEQ ID NO: 7 and 39, respectively, the numbering of Asncorresponding to the polypeptide sequence of SEQ ID NO: 7 and 39, respectively comprisingglutamine or pyroglutamate at X1; and the amino acids at position X2, X3, X4, and X5 of SEQID NO: 7 and 39, respectively are either modified unmodified, preferably unmodified.In embodiments of the disclosure, the antibody of the present disclosure comprises two HCsand two LCs, wherein the heavy chain, each independently, has an amino acid sequence setforth in SEQ ID NO: 9, and the light chain, each independently, has an amino acid sequenceset forth in SEQ ID NO: 8. In a preferred embodiment, the heavy chain of the anti-TTR antibody of the present disclosureis devoid of the C-terminal lysine as shown in SEQ ID NO: 9 and the glutamine at the N-terminus, as shown in SEQ ID NO: 9, is modified as pyro-glutamic acid. Said sequence, i.e.,the sequence of the heavy chain with a clipped off C-terminal lysine and a cyclized N-terminal glutamine (e.g., cyclized modification of glutamine to pyroglutamate) is set forth in SEQ ID NO: 12.In some embodiments, the antibody of the present disclosure may have undergone other post-translational modifications (PTMs), such as, e.g., partial cleavage, oxidation, deamidation,succinimidation, pyroglutamate formation, and isomerization. A plurality of such PTMs maybe present, in any combination. In embodiments, the PTMs are in the heavy chain polypeptide sequence; however, the light chain polypeptide sequence may also be post-translationallymodified. The experimentally determined PTMs in NI006 / ALXN2220 are provided in detail inExample 2. In particular, in addition to the above-mentioned C-terminal lysine clipping andcyclization of the N-terminal glutamine to pyroglutamate, the heavy and / or light chains of theantibody may contain methionine (M) oxidation, e.g., at HC position 255; asparagine (N)deamidation, e.g., at HC position 318 and / or at HC position 387; asparagine (N) succinimide formation, e.g., at HC position 318; and / or amidation of the C-terminal proline (P) after the loss of the C-terminal lysine and glycine. In addition, or alternatively, the antibody is glycosylated, in particular N-glycosylated. More particularly, the heavy chain of the antibody is glycosylated and even more particularly at N300of the heavy chain (SEQ ID NO: 9).In a preferred embodiment, the HC chain of the anti-TTR antibody of the present disclosurelacks the C-terminal lysine, has a modified glutamine at the N-terminus as pyro-glutamic acid and comprises at least one N-glycosylation site. Thus, in one preferred embodiment, theantibody of the present disclosure is composed of two heavy chains having SEQ ID NO: 9, andtwo light chains having SEQ ID: 8, and wherein in the heavy chain the glutamine at the N- terminus is modified as pyro-glutamic acid, the C-terminal lysine is cleaved or absent, and theheavy chain is N-glycosylated. In other words, the antibody is composed of two heavy chainshaving SEQ ID NO: 12 (preferably wherein the N-terminus of each antibody HC is cyclized),and two light chains having SEQ ID NO: 8, and wherein each heavy chain is N-glycosylated,e.g., at Asn300.In a further preferred embodiment, the antibody has a low abundance of the other PTMs (preferably around or less than 5% as referred to further above). Such antibodies are particularly favorable for therapeutic purposes since they are stable, safe, efficient, have a long-half life, reduced immunogenicity and show charge homogeneity. These favorable features are confirmed in Examples 3 and 4. In particular, the stability studies in Example 4 show that the antibody formulation is long term stable and also batch analysis in Example 3 confirmed that the antibodies are stable. For example, SEC analysis confirms that there are nearly no high or low molecular weight species in the sample (no aggregation or degradation). In an embodiment of the present disclosure, the antibody comprises an HC having the amino acid sequence of SEQ ID NO: 9 and an LC having the amino acid sequence of SEQ ID NO: 8,wherein the glutamine (Q) at position 1 of SEQ ID NO: 9 is modified to a pE, the lysine (K) atposition 450 of SEQ ID NO: 9 is clipped off (e.g., via proteolytic digestion), the asparagine (N) at position 300 of SEQ ID NO: 9 is glycosylated, and the antibody comprises the following disulfide bridges: LC:C23-LC:C88; LC:C134-LC:C194; LC:C214-HC:C223; HC:C22- HC:C97; HC:C147-HC:C203; HC1:229-HC2:229 and HC1:232-HC2:232; HC:C264- HC:C324; and HC:C370-HC:C428. The numbering of the foregoing cysteine residuescorrespond to their positions in SEQ ID NOs: 9 and 8, respectively. Additionally, the antibodycomprises glycans, wherein the glycans are Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2 type glycans. In preferred embodiments,the glycans are mostly G0F and G1F type glycans. In some embodiments, the HC set forth inSEQ ID NO: 9 further comprises one or more modifications: the asparagine (N) at position 58 is deamidated; the methionine (M) at position 71 is oxidized; the methionine (M) at position 115 is oxidized; the methionine (M) at position 225 is oxidized; the aspartate (D) at position 283 is isomerized; the asparagine (N) at position 318 is deamidated or comprises a succinimide; the methionine (M) at position 361 is oxidized; the asparagine (N) at position 387 is deamidated or comprises a succinimide; the methionine (M) at position 431 is oxidized; the glycine (G) at position 449 is absent; the proline (P) at position 448 is amidated after the loss of the C-terminal lysine and glycine. Furthermore, as mentioned above, each heavy chain of antibody NI006 / ALXN2220 maycontain a single N-linked glycosylation site at Asn300. The N-linked glycosylation structure ispredominantly a fucosylated, complex biantennary glycan with 0 galactose residues (G0F) (about 49 %) or with 1 galactose residue (G1F) (about 25 %). The detailed glycosylation profileis shown in Examples 2 and 3. Glycosylation plays a vital role in the stability, in vivo activity,solubility, serum half-life and immunogenicity of many therapeutic proteins. N-glycan analysis determines the relative distribution of N-glycans released from the glycoprotein and provides insightful information on the safety and efficacy of bio-therapeutics.Thus, in a preferred embodiment, the antibody of the present disclosure is an IgG antibody,particularly of the IgG1m3 subtype, and has a heavy chain which is N-glycosylated, preferablywherein the N-linked glycosylation site is Asn300. A more detailed analysis of the glycan structure showed that more than 85% of the glycans are fucosylated, in particular about 89% to 94% of the glycans. It has been also shown that about80% to 90% of the glycans are part of the major fucosylated glycan types, meaning that themajority of glycan structures attached to the antibody contain a fucose residue. The fucosylation profile is dependent on the cell line in which the antibody has been produced and thus, thefucosylation profile is specific for the antibody of the present invention. Furthermore, such afucosylation profile is advantageous since fucosylation can improve the structural stability of the glycan structure on the antibody, which contributes to a longer in vivo half-life, which canreduce dosing frequency and improve patient compliance. Moreover, highly fucosylatedantibodies are usually less likely to elicit an immune response in patients, as fucosylated glycansare common in human antibodies and less likely to be recognized as foreign. High fucosylationlevels are easier to achieve consistently with certain cell lines (like CHO cells) and are generallymore reliable for large-scale manufacturing and a consistent product is obtained, which iscrucial for regulatory approval and therapeutic efficacy. Accordingly, the antibody of the present disclosure preferably comprises the following glycan types: Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2, preferably wherein the major glycan types are G0F and G1F. More preferably, the antibody of the present disclosure comprises glycans, wherein more than 85% of the glycans are fucosylated, preferably wherein about 85% to 95% of the glycans are fucosylated, more preferably wherein about 89% to 94% of the glycans are fucosylated. Furthermore, it has been shown that about 27% to 38% of the glycans are galactosylated, preferably about 27% to 38%. Thus, the antibody shows a controlled glycosylation profile which is important for quality control in antibody production, as consistent glycosylation patterns contribute to predictable efficacy, safety, and stability. Furthermore, galactosylation contributes to structural stability being important for maintaining a consistent therapeutic effect over time, which is advantageous for long-term antibody administration. Accordingly, in oneembodiment, the antibody of the present disclosure comprises glycans, wherein about 20% to40% of the glycans are galactosylated preferably about 27% to 38%.Analysis of the glycan structure showed that about 1% to 4% of the glycans are mannose-containing glycans of the Man5 and Man31F type. Usually, high levels of mannose structureslike Man5 can indicate incomplete processing in the glycosylation pathway, so a low percentage(like in the present case) is generally favorable in therapeutic antibodies since it shows that theantibody production process is well-controlled, with most glycans processed to more complex structures. Furthermore, since mannose-rich glycans are less common in human antibodies and can sometimes increase immunogenicity, as the immune system might recognize them as foreign, a low mannose percentage is favorable for therapeutic applications of the antibody. Thus, in one embodiment, the antibody of the present disclosure comprises glycans, wherein about 1% to 4% of the glycans are mannose-containing glycans, preferably wherein the glycans are of the Man5 and Man31F type, and more preferably wherein about 1% to 4% of the glycansare of the Man5 type. In most batches that have been analyzed, the mannose-containing glycansare present in an even lower amount, in particular between 1% and 2%. Accordingly, more preferably, the antibody of the present disclosure comprises glycans, wherein about 1% to 2% of the glycans are mannose-containing glycans, preferably wherein the glycans are of the Man5 and Man31F type, and more preferably wherein about 1% to 2% of the glycans are of the Man5 type. Finally, glycan analysis showed that about 0.5% to 2% of the glycans are siaylated and thus, inone embodiment, the antibody of the present disclosure comprises glycans, wherein less than2% of the glycans are siaylated, preferably wherein about 0.5% to 2% of the glycans are siaylated. As regards the mannose-containing glycans, it has been surprisingly shown that reducing pHdead band from 0.20 to 0.05 (with a pH set to 6.9) led to reduction on Man 5 (see Example 3),which is favorable as explained above. In particular, the amount of Man5 type glycans is nearlyhalved. Thus, in a particular preferred embodiment, less than 3% of the glycans are of the Man5type, preferably less than 2.9%, preferably less than 2.8%, preferably less than 2.7%, preferably less than 2.6%, preferably less than 2.5%, preferably less than 2.4%, preferably less than 2.3%,preferably less than 2.2%, preferably less than 2.1%, preferably less than 2.0%, preferably lessthan 1.9%, preferably less than 1.8%, preferably less than 1.7%, preferably less than 1.6%,preferably less than 1.5%, preferably less than 1.4%, preferably less than 1.3%, preferably lessthan 1.2%, preferably less than 1.1%, preferably less than 1.0%, preferably less than 0.9%,preferably less than 0.8%, preferably less than 0.7%, preferably less than 0.6%, preferably lessthan 0.5%, preferably less than 0.4%, preferably less than 0.3%, preferably less than 0.2%,preferably less than 0.1%, preferably less than 0%. In a further preferred embodiment, about2%, preferably between 2.5% and 1%, more preferably between about 2% and 1% of the glycans are of the Man5 type (see Table 9). Thus, embodiments of the disclosure further relate to methods and workflows for obtaining ALXN2220 with a desired product profile. Specifically, as described in detail in Example 3, reducing the pH dead band from 0.20 to 0.05 led to considerable reduction in acidic species,e.g., from about 37% to about 29% in ALXN2220 process A2 and a general changed chargedvariant profile. Quite surprisingly, reducing pH dead band from 0.20 to 0.05 also led to appreciable reduction, e.g., about 50% reduction, in Man 5 levels (from about 3.8% to about 1.9%). Accordingly, embodiments of the methods and workflows described herein provide a robust control of high mannose species in the antibody drug substance batches, without concomitant adverse impact on other product quality attributes, such as, for example, relative levels (in %) of main vs. HMW vs. LMW antibody species (as determined by SEC); levels (in %) of main antibody species, as determined using capillary electrophoresis sodium dodecyl sulfate under non-reduced conditions (CE-SDS-NR); and levels of antibody heavy and light chains (in %), as determined using capillary electrophoresis sodium dodecyl sulfate under reduced conditions (CE-SDS R). Further analysis revealed that an antibody sample comprises basic and acid antibody variants, dependent on their post-translational modifications. For example, antibodies comprising deamidated asparagine residues at positions N58, N328 and / or N387 of their HC, comprises sialyated N-glycosylation, galactosylated N-glycosylation, HC truncation between N58 andT59 as well as lysine glycation distributed evenly across all lysine in antibody’s HC and LC asreferred to further above belong to the acidic species and antibodies comprising aspartate isomerization at D283 of their HC, lysine loss at K450 of the HC and proline amidation with glycine and lysine loss in their HC (P448) as referred to further above belong to the basic species. Accordingly, in one embodiment, the antibody of the present disclosure is an acidic antibody variant. In another embodiment, the antibody of the present disclosure is a basic antibody variant. In another embodiment, the antibody of the present disclosure is a neutral antibody variant. In a preferred embodiment, the antibody of the present disclosure is an acidic antibody variant. In some embodiments, the disclosure relates to antibodies that are recombinant, e.g., generatedvia expression in a suitable host cell such as bacterial (e.g., E. coli) cells or cells of othermicroorganisms such as yeast cells; or mammalian cells such as CHO cells. In embodiments ofthe disclosure, the recombinant antibody comprises an N-linked glycosylation structure whichis predominantly a glycan with 0 galactose residues (G0F) (about 49 %) or with 1 galactose residue (G1F) (about 25 %). Most preferably, the antibody comprises or consists essentially ofthe glycosylation profile as shown in Example 2 and referred to above.In embodiments, the theoretical molecular weight (MW) of the antibody of the presentdisclosure is about 144.2 kDa, and the molecular weight determined by mass spectrometry (MS)is about 144.2 kDa (deglycosylated form). In embodiments, the molecular weight of theantibody of the disclsoure, as determined by mass spectrometry (MS) is between 147.0 and 147.6 kDa (intact IgG1).Embodiments of the disclosure further relate to pharmaceutical compositions comprising theantibody of the present disclosure, as characterized above, which has a molecular weight ofabout 150 kDa, preferably a MW of about 147 kDa.In embodiments, the experimentally determined pI of the antibody of the present disclosure isabout 9.3 and the theoretical pI is about 8.4. In embodiments, the experimentally determinedextinction coefficient of the antibody of the present invention is 1.390 and the theoretically determined extinction coefficient is 1.438.In some embodiments, the antibodies of the present disclosure comprise human IgG antibodiescomprising two identical heavy chains (HCs) and two identical light chains (LCs), wherein theidentity may be based on sequence identity, i.e., wherein the primary amino acid sequence ofthe heavy chain polypeptide sequence(s), which make up the antibody tetramer, optionally ortogether with the primary amino acid sequence of the light chain polypeptide sequence(s),which make up the antibody tetramer, are identical. The four chains are stabilized by intra-chainand inter-chain disulfide bonds, wherein the positions of the disulfide bridges, which have been identified per Lys-C and trypsin digestion and subsequent LC-MS (see Example 2) are the following: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in theantibody HC sequence of SEQ ID NO: 7 and the antibody LC sequence of SEQ ID NO: 8, withSEQ ID NO: 7 having the N-terminal glutamine or pyroglutamate (X1).Thus, in one embodiment, the antibody of the present disclosure comprises at least 1, at least 2,at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 disulfide bridges, preferably atthe above-identified positions. In embodiments, the antibodies of the present disclosurecomprise a plurality of, e.g., all 8, disulfide (DS) bridges selected from bridges between thelight chain (LC) and LC; bridges between the LC and the heavy chain (HC); and bridgesbetween the HC and HC. In embodiments, the antibodies of the disclosure comprises DSbridges selected from (1) LC:C23-LC:C88; (2) LC:C134-LC:C194; (3) LC:C214-HC:C223;(4) HC:C22-HC:C97; (5) HC:C147-HC:C203; (6) HC1:229-HC2:229 and HC1:232-HC2:232;(7) HC:C264-HC:C324; and (8) HC:C370-HC:C428, wherein LC designates antibody lightchain; HC designates antibody heavy chain; C designates cysteine amino acid; and the numberdesignates the position of said cysteine in the antibody HC sequence of SEQ ID NO: 7comprising glutamine or pyroglutamate at X1 (i.e., X1 is not absent in SEQ ID NO: 7) and / orthe antibody LC sequence of SEQ ID NO: 8.To avoid generation of "anti-drug antibodies" (ADA) by a subject administered an antibody or antigen-binding fragment thereof described herein, the antibody is preferably a human or humanized antibody, typically human IgG and most preferably a human IgG1. In a preferredembodiment, the antibody is a human IgG1m3 allotype and comprises preferably a kappa LCconstant region. Most preferably, the closest human gene / allele of the variable domains are IGKV1-3901 (93.3%) + IGKJ101 (100%) and IGHV4-30-201 (89.5%) + IGHJ302 (100%). Antibodies, like many other proteins, are secreted from the cells via the co-translational translocation pathway. In eukaryotes, a signal peptide that contains 5–30 amino acids present at the N-terminus of nascent proteins is recognized by the signal recognition particle (SRP) in the cytosol while the protein is still being synthesized on the ribosome. The SRP then delivers the SRP-ribosome-nascent chain (SRP-RNC) complex to the SRP-receptor (SR) in the endoplasmic reticulum (ER) membrane. GTP-dependent mechanisms then deliver the RNC complex to a membrane-bound translocon which allows translocation of the growing polypeptide chain into the lumen of the ER. After crossing the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP), Human IgG antibodies consist of two identical heavy chains (HCs) and two identical light chains (LCs). Efficient expression of the HC and LC requires signal peptides for the transport of the HC and the LC polypeptides into the ER for proper folding, assembly and post-translational modification.Thus, in one embodiment, the HC of the antibody of the present disclosure further comprises asignal peptide, wherein the signal peptide is derived from a human immunoglobulin heavychain, and the LC of the antibody of the present disclosure further comprises a signal peptide,wherein the signal peptide derived from a human immunoglobulin kappa light chain. Such signal peptides are commonly known in the art and its sequences can be derived from pertinent databases, for example from the database of the National Institutes of Health (NIH) or the European Molecular Biology Laboratory (EMBL) database and the EMBL's European Bioinformatics Institute (EBI) database, respectively. Furthermore, WO 2014 / 058389 A1 discloses various signal peptides that can in principle be used for cloning. In the present case,the signal peptides as set forth in SEQ ID NOs: 17 and 18 have been used for the expression ofthe HC and LC, respectively, of the antibody of the present disclosure which resulted in anefficient expression of the HC and LC, thus being transported to the ER for proper folding,assembly and post-translational modification, leading to an antibody particularly suitable for formulating in a pharmaceutical composition. Accordingly, in a preferred embodiment, the HC of the antibody of the present disclosure further comprises a signal peptide having an amino acid sequence of SEQ ID NO: 17, wherein the sequence including the HC and the signal peptide is set forth in SEQ ID NO: 19. In addition,or alternatively, the LC of the antibody of the present disclosure further comprises a signalpeptide having an amino acid sequence of SEQ ID NO: 18, wherein the sequence including the HC and the signal peptide is set forth in SEQ ID NO: 20. As is understood in the art, some antibodies can tolerate different signal peptides, whereasothers are more restricted. The above signal peptides for the heavy chain and light chainantibody sequences represent an optimal pair of signal peptides for the expression of NI006 / ALXN2220 recombinantly, e.g., in CHO cells.The present disclosure further relates to polynucleotides encoding the antibody of the presentdisclosure. In particular, the present disclosure relates to one or more polynucleotides(s),preferably to two polynucleotides which encode the antibody of the present disclosure, i.e., thefirst polynucleotide comprises a nucleotide sequence encoding the HC and the second polynucleotides comprises a nucleotide sequence encoding the LC of the antibody. Preferably,the disclosure relates to polynucleotides encoding the antibody HC and the LC, wherein the HChas the amino acid sequence of SEQ ID NO: 7 (with no modifications, i.e., glutamine orpyroglutamate (X1), and wherein both lysine (X7) and glycine (X6) are present, and X2, X3,X4, and X5 are unmodified) and wherein the LC has the amino acid sequence of SEQ ID NO:8. The disclosure further relates to polynucleotides encoding the antibody HC and the LC,wherein the HC has the amino acid sequence of SEQ ID NO: 9 (with modifications in thesequence of SEQ ID NO: 7 comprising deletion of C-terminal lysine and cyclization of N-terminal glutamine into pyroglutamate) and wherein the LC has the amino acid sequence of SEQ ID NO: 8.Accordingly, the disclosure further relates to polynucleotides encoding the antibodies of theforegoing, wherein a first polynucleotide comprises the nucleotide sequence set forth in SEQID NO: 13 which encodes the antibody HC and a second polynucleotide comprises thenucleotide sequence set forth in SEQ ID NO: 14 which encodes the antibody LC.The disclosure further relates to codon-optimized nucleic acids, for example, for efficientexpression in the CHO cell line. Thus, in one embodiment, the first polynucleotide of thepresent disclosure comprises the nucleotide sequence encoding the antibody HC set forth inSEQ ID NO: 15 and a second polynucleotide comprises the nucleotide sequence encoding theantibody LC set forth in SEQ ID NO: 16.In one embodiment, the polynucleotides of the present disclosure further comprise a nucleotidesequence encoding a signal peptide. In particular, in one embodiment, the first nucleotide sequence comprises a nucleotide sequence encoding a signal peptide derived from a human immunoglobulin heavy chain and the second nucleotide sequences comprises a nucleotide sequence encoding a signal peptide derived from a human immunoglobulin kappa light chain. In a preferred embodiment, the nucleotide sequence of the first signal peptide is set forth in SEQ ID NO: 21, wherein the first nucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 23. In addition, the nucleotide sequence of the second signal peptide is set forth in SEQ ID NO: 22, wherein the first nucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 24. In accordance with the present disclosure, the above nucleic acids encoding the signal peptides for the heavy chain and light chain antibody sequences represent an optimal pair of signalpeptide-encoding nucleic acids, e.g., for the expression of the respective heavy and light chainpolypeptide sequences of NI006 / ALXN2220 recombinantly, e.g., in CHO cells.The present disclosure also relates to a nucleic acid molecule which is(a) polynucleotide(s) comprising a first nucleotide sequence set forth in SEQ ID NO: 13, and asecond nucleotide sequence set forth in SEQ ID NO: 14;(b) messenger RNA (mRNA) equivalent of the first and the second nucleotide sequences of (a); (c) polynucleotide(s) comprising sequences which are complementary to the first and the second nucleotide sequences of (a) or the mRNA equivalent thereof of (b); or (d) polynucleotide(s) comprising sequences which are degenerates of the first and the second nucleotide sequences of (a) or the mRNA equivalent thereof of (b). In a preferred embodiment, the polynucleotide(s) of (d) comprise a first nucleotide sequenceset forth in SEQ ID NO: 15, and a second nucleotide sequence set forth in SEQ ID NO: 16. Thedegenerate sequences disclosed herein represent codon optimized nucleic acid sequences that confer optimal recombinant expression of the respective heavy and light chains of the antibody in a cell that is suitable for commercial manufacturing, e.g., CHO cells. In one embodiment, the polynucleotides of the present disclosure further comprise a nucleotide sequence encoding a signal peptide. In particular, in one embodiment, the first nucleotide sequence comprises a nucleotide sequence encoding a signal peptide derived from a human immunoglobulin heavy chain and the second nucleotide sequences comprises a nucleotide sequence encoding a signal peptide derived from a human immunoglobulin kappa light chain. In a preferred embodiment, the nucleotide sequence of the first signal peptide is set forth in SEQ ID NO: 21, wherein the first nucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 23. In addition, the nucleotide sequence of the second signal peptide is set forth in SEQ ID NO: 22, wherein the first nucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 24.The disclosure further relates to both pre-processed (e.g., pre-protein) as well as processed (e.g.,mature) forms for each of the antibody heavy and light chain polypeptides, which are encodedby the aforementioned nucleic acids, e.g., nucleic acid sequences set forth in SEQ ID NO: 13or 15 (encoding the pre-protein antibody heavy chain) and SEQ ID NO: 14 or 16 (encoding thepre-protein antibody light chain).The present disclosure further relates to one or more expression vectors comprising thepolynucleotides / nucleic acid molecules of the present disclosure and to host cells comprisingsaid vector(s) and / or polynucleotides / nucleic acid molecules of the present disclosure.As described in Example 1, the antibody of the present disclosure is produced in CHO cells, inparticular in the CHO cell line K1. Thus, in one embodiment, the host cell is a non-human cell, preferably a CHO cell, most preferably CHO-K1. For recombinant production of the antibody,also microbial, for example E. coli cells, or insect cells can be used.The present disclosure further relates to a method of manufacturing the antibody of the presentdisclosure which comprises at least culturing the host cell, preferably the CHO cell, mostpreferably the CHO K1 cell comprising the polynucleotide(s) of the present disclosure,preferably in the form of the vector(s) of the present disclosure and isolating the antibody fromthe culture. As an example, in some embodiments, a method of manufacturing an antibody as described herein produces an antibody comprising an HC having the amino acid sequence of SEQ ID NO: 7 and 39, respectively and an LC comprising the amino acid sequence of SEQ ID NO: 8. In embodiments, the antibodies comprise an HC having the amino acid sequence of SEQ ID NO:7 and 39, respectively, wherein N-terminal residue X1 is absent or present as glutamine or pE.In embodiments, X2 is methionine or oxidized methionine. In embodiments, X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X4 is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X5 is proline or amidated proline. In embodiments, X6 is absent or glycine. In embodiments, X7 is absent or lysine. In embodiments, XI is asparagine or deamidated asparagine. In embodiments, XIIis methionine or oxidized methionine. In embodiments, XIIIis methionine or oxidized methionine. In embodiments, XIVis aspartate or iso-aspartate. In embodiments, XVis asparagine or glycosylated asparagine. In embodiments, XVI is methionine or oxidized methionine. In embodiments, XVII is methionine or oxidized methionine. In further embodiments, X1is pE and / or X7is absent.The present disclosure further relates to a composition comprising the antibody of the presentdisclosure. Thus, in one embodiment, the composition comprises the antibody with or withoutthe PTMs as defined hereinbefore. In a preferred embodiment, the composition comprises amixture of the antibodies as defined hereinbefore. As shown in Examples 2 and 3, about 99%to 100% of the antibodies present in a sample of a typical antibody composition have a N- terminal pyro-glutamic acid in the heavy chain and about 96% of the antibodies have a loss of the C-terminal lysine. Thus, in one embodiment, about 99% (99% to 100%) of the antibodiesin the formulation of the present disclosure have a heavy chain wherein the N-terminal pyro-glutamic acid is modified from N-terminal glutamine and / or about 96% (95% to 96%) of theantibodies are without (or devoid of) the C-terminal lysine. Absence of C-terminal lysine maybe a result of proteolytic cleavage of the antibody heavy chain containing said lysine or due toantibody engineering, e.g., via mutation or deletion of the triplet codon that encodes the HC C-terminal lysine in the nucleic acid encoding said HC. Preferably, the antibodies present in saidcomposition further comprise the N-glycosylated HC as defined hereinbefore. For instance, in embodiments, the composition comprises antibodies, wherein the antibodies comprise an HC having the amino acid sequence of SEQ ID NO: 7 and 39, respectively and a light chain having the amino acid sequence of SEQ ID NO: 8. In embodiments, the antibodiescomprise an HC having the amino acid sequence of SEQ ID NO: 7 and 39, respectively, whereinN-terminal residue X1is absent or present as glutamine or pE. In embodiments, X1is PE for 99% to 100% of the antibodies of the composition, preferably wherein X1 is PE for 99.9% of the antibodies of the composition. In embodiments, X2 is methionine or oxidized methionine. In embodiments, X3is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X4 is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X5 is proline or amidated proline. In embodiments, X6is absent or glycine. In embodiments, X7is absent or lysine. In embodiments, XIis asparagine or deamidated asparagine. In embodiments, XII is methionine or oxidized methionine. In embodiments, XIII is methionine or oxidized methionine. In embodiments, XIV is aspartate or iso-aspartate. In embodiments, XVis asparagine or glycosylated asparagine. In embodiments, XVIis methionine or oxidized methionine. In embodiments, XVIIis methionine or oxidized methionine. In embodiments, the composition comprises antibodies, wherein the antibodies comprise an HChaving the amino acid sequence of SEQ ID NO: 7 and 39, respectively and a light chain havingthe amino acid sequence of SEQ ID NO: 8. In embodiments, the antibodies comprise an HChaving the amino acid sequence of SEQ ID NO: 7 and 39, respectively, wherein N-terminalresidue X1 is absent or present as glutamine or pE. In embodiments, X2 is methionine or oxidized methionine. In embodiments, X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X4is asparagine, deamidated asparagine, or asparagine comprising a succinimide. In embodiments, X5is proline or amidated proline. In embodiments, X6 is absent or glycine. In embodiments, X7 is absent or lysine. In embodiments, X7is absent in about 95% to about 96% of the antibodies of the composition, preferably wherein X7is absent for 95.8% of the composition. In embodiments, XIis asparagine or deamidated asparagine. In embodiments, XIIis methionine or oxidized methionine. In embodiments, XIIIis methionine or oxidized methionine. In embodiments, XIV is aspartate or iso-aspartate. In embodiments, XV is asparagine or glycosylated asparagine. In embodiments, XVI is methionine or oxidized methionine. In embodiments, XVIIis methionine or oxidized methionine. In embodiments, a portion of the antibodies of the composition are fragmented in the HC via clipping between asparagine at position 58 and threonine at position 59, as set forth in SEQ IDNO: 7 and 39, respectively. In some embodiments, about 10%, about 20%, about 30%, about40%, about 50%, about 60%, about 70%, about 80%, about 90% or more of the antibodies of the composition are fragmented. In addition, but to a minor extent and preferably in negligible amounts, some antibody species may be found in the composition that may have undergone other post-translational modifications (PTMs) such as partial cleavage, oxidation, deamidation, succinimide or pyroglutamate formation and isomerization. The PTMs identified to be present in NI006 / ALXN2220 are referred to in Example 2. In particular, next to the above-mentioned C- terminal lysine clipping and cyclization of the N-terminus, the antibody may show methionine (M) oxidation, e.g., at HC position 255; asparagine (N) deamidation, e.g., at HC position 318 and / or at HC position 387; asparagine (N) succinimide formation, e.g., at HC position 318; and / or amidation of the C-terminal proline (P) after the loss of the C-terminal lysine and glycine. In other words, the composition of the present disclosure comprises in one embodiment one ormore antibodies comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acidsequence of SEQ ID NO: 8, wherein in one or more of the antibodies the HC is preferably modified as follows:the glutamine (Q) at position 1 is modified to pyroglutamate (pE),the asparagine (N) at position 300 is glycosylated; and / or the lysine (K) at position 450 is absent, preferably wherein the glutamine (Q) at position 1 ismodified to pyroglutamate (pE), the asparagine (N) at position 300 is glycosylated, and thelysine (K) at position 450 is absent, The composition of the present disclosure comprises in one embodiment one or more antibodies with the following additional modifications in their HC: the methionine (M) at position 255 is oxidizedthe asparagine (N) as position 318 is deamidated or comprises a succinimide;the asparagine (N) at position 387 is deamidated;the proline (P) at position 448 is amidated; and / orthe glycine (G) at position 449 is absent.In embodiments, the composition of the present disclosure comprises one or more antibodies with the following additional modifications in their HC:the asparagine (N) at position 58 is deamidatedthe methionine (M) at position 71 is oxidized, the methionine (M) at position 115 is oxidized the methionine (M) at position 255 is oxidized the aspartate (D) at position 283 is iso-aspartate the methionine (M) at position 361 is oxidized, and / orthe methionine (M) at position 431 is oxidized.In a preferred embodiment, the antibodies comprised in the composition of the present disclosure are produced via recombinant expression in CHO-K1 cells. In a particular embodiment, the composition of the present disclosure comprises one or more antibodies which comprise a pyro-glutamic acid at the N-terminal of the heavy chain sequence instead of glutamine, preferably wherein in more than 90%, preferably in about 99% to 100% of the antibodies the glutamine (Q) at position 1 of SEQ ID NO: 9 is modified to pyroglutamate. In a further particular embodiment, the composition of the present disclosure comprises one or more antibodies in which the lysine (K) at position 450 of SEQ ID NO: 9 is absent, preferably wherein in more than 90%, preferably in about 95% to 100%, preferably in about 95% to 96% of the antibodies the lysine (K) at position 450 of SEQ ID NO: 9 is absent. In a further particular embodiment, the composition of the present disclosure comprises one or more antibodies in which the lysine (K) at position 450 of SEQ ID NO: 9 is absent, preferably wherein in more than 90%, preferably in about 95% to 100%, preferably in about 95% to 96% of the antibodies the lysine (K) at position 450 of SEQ ID NO: 9 is absent and which comprise a pyro-glutamic acid at the N-terminal of the heavy chain sequence instead of glutamine, preferably wherein in more than 90%, preferably in about 99% to 100% of the antibodies the glutamine (Q) at position 1 of SEQ ID NO: 9 is modified to pyroglutamate.In a preferred embodiment, the asparagine residues (N) at positions 58, 318, and 387 in the oneor more antibodies are not deaminated and do not comprise a succinimide and the compositiondoes comprise no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the asparagine residues (N) at positions 58, 318, and / or 387 are deamidated, respectively. In a further preferred embodiment, the methionine residues atpositions 71, 115, 255, 361 and 431 in the one or more antibodies are not oxidized and thecomposition comprises no antibodies or only a low amount of antibodies, for example less thanabout 5% of the antibodies, in which the methionine residues at positions 71, 115, 255, 361 and / or 431 are oxidized. In a further preferred embodiment, the aspartate at position 283 in theone or more antibodies is not isomerized and the composition comprises no antibodies or onlya low amount of antibodies, for example less than about 5% of the antibodies, in which the aspartate at position 283 is isomerized, respectively. In a further preferred embodiment, the glycine at position 449 in the one or more antibodies is not absent, i.e., the glycine is present and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the glycine at position 449 is absent, respectively, i.e., the composition mainly comprises antibodies in which the glycine is present. Consequently, preferably, the proline at position 448 in the one or more antibodies is not amidated and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the proline at position 448 is amidated. In more detail, the composition of the present disclosure comprises in embodiments one or more antibodies, preferably less than about 5%, preferably less than 2%, preferably less than about 1%,preferably about 0% to 1% in which the asparagine (N) at position 58 of SEQ ID NO: 9 isdeamidated. In addition, or alternatively, the composition of the present disclosure comprises one or more antibodies, preferably less than about 8%, preferably about 6% to 9% in which theasparagine (N) at position 318 of SEQ ID NO: 9 is deamidated. In addition, or alternatively, thecomposition of the present disclosure comprises one or more antibodies, preferably less thanabout 3%, preferably about 1% to 3% in which the asparagine (N) at position 387 of SEQ ID NO: 9 is deamidated. In addition, or alternatively, the composition of the present disclosurecomprises one or more antibodies, preferably less than about 5%, preferably less than about2%, preferably less than about 1%, preferably about 0% to 1% in which the methionine (M) at position 71 of SEQ ID NO: 9 is oxidized. In addition, or alternatively, the composition of thepresent disclosure comprises one or more antibodies, preferably less than about 5%, preferablyless than about 3%, preferably less than about 2, preferably about 1% to 3%, in which the methionine (M) at position 115 of SEQ ID NO: 9 is oxidized. In addition, or alternatively, thecomposition of the present disclosure comprises one or more antibodies, preferably less thanabout 5%, preferably less than about 3%, preferably about 1% to 30%, in which the methionine(M) at position 255 of SEQ ID NO: 9 is oxidized. In addition, or alternatively, the compositionof the present disclosure comprises one or more antibodies, preferably less than about 5%,preferably less than about 2%, preferably less than about 1%, preferably about 0% to 1% inwhich the methionine (M) at position 361 of SEQ ID NO: 9 is oxidized. In addition, oralternatively, the composition of the present disclosure comprises one or more antibodies,preferably less than about 5%, preferably less than about 3%, preferably less than about 2%,preferably about 1% to 2% in which the methionine (M) at position 431 of SEQ ID NO: 9 isoxidized. In addition, or alternatively, the composition of the present disclosure comprises oneor more antibodies in which the aspartate (D) at position 283 of SEQ ID NO: 9 is modified toiso-aspartate. In addition, or alternatively, the composition of the present disclosure comprisesone or more antibodies in which the proline (P) at position 448 of SEQ ID NO: 9 is amidated.In addition, or alternatively, the composition of the present disclosure comprises one or moreantibodies in which the glycine (G) at position 449 of SEQ ID NO: 9 is absent. In addition, oralternatively, the composition of the present disclosure comprises one or more antibodies whichare fragmented via clipping between asparagine at position 58 and threonine at position 59 of SEQ ID NO: 9. In addition, or alternatively, the composition of the present disclosure comprises one or more antibodies, preferably less than about 6%, preferably less than about 5%, preferablyabout 2% to 5% in which the heavy chain is glycated. In addition, or alternatively, thecomposition of the present disclosure comprises one or more antibodies, preferably less thanabout 4%, preferably less than about 3%, preferably about 1% to 3% in which the light chain isglycated. Furthermore, the composition comprises one or more antibodies with a glycan profile as defined above in detail. As referred to above, the composition of the present disclosure comprising the antibodies with the indicated PTMs is favorable for therapeutic purposes since such a composition is stable, safe, efficient, less immunogenic, functional and can be reliable reproducible manufactured (see Example 4). Same characterization can also be used to characterize the antibody of the present invention.The antibody of the present disclosure has been shown to be particularly stable in an aqueousformulation comprising about 50 mg / mL or 100 mg / mL of the antibody, 20 mM histidine,sucrose at a concentration of 65 mg / ml (6.5% (w / v)) or 80 mg / ml (8 % (w / v)), polysorbate 80(PS) at a concentration of 0.03% (w / v) (0.3 mg / mL), at pH of 5.8. As shown in Example 4, theshelf-life for the drug product formulated in the above-mentioned aqueous formulation is currently set at 24 months stored at 5 ^^3 ^C, protected from light.Thus, the present disclosure relates to a composition comprising from about 25 mg / mL to about150 mg / mL of the antibody of the present disclosure, preferably comprising about 50 mg / mLor 100 mg / mL of the antibody of the present disclosure, and further comprising histidine at aconcentration of about 20 mM (e.g., L-Histidine 1.06 mg / mL and L-Histidinemonohydrochloride 2.78 mg / mL), sucrose at a concentration of about 50 mg / ml to about 80 mg / ml, preferably 65 mg / ml (6.5% (w / v)) or 80 mg / ml (8 % (w / v)), polysorbate 80 (PS) at a concentration of about 0.01% (w / v) to about 0.5% (w / v), preferably of about 0.03% (w / v) (0.3 mg / mL), and having a pH of about 5.3 to 6.3, preferably of about 5.8. In one preferredembodiment, the antibody is composed of two HCs having SEQ ID NO: 7 or 9 and two LCshaving SEQ ID: 8, and wherein preferably in each HC the glutamine (X1of SEQ ID NO: 7 and Q at position 1 of SEQ ID NO: 9, respectively) at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7 of SEQ ID NO: 7 and K at position 450 of SEQ ID NO: 9) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is atposition Asn300 of SEQ ID NO: 9, wherein the amino acids at position X2, X3, X4, and X5 ofSEQ ID NO: 7 are either modified or unmodified, preferably unmodified or wherein themethionine at position M255 of SEQ ID NO: 9 is not oxidized, the asparagine at positions N318 and N387 of SEQ ID NO: 9 is not deamidated and does not comprise a succinimide, and theproline at position P448 of SEQ ID NO: 9 is not amidated, and wherein the glycine (X6 of SEQID NO: 7 and G at position 449 of SEQ ID NO: 9) is present and not clipped off.. In onepreferred embodiment, the antibody is composed of two HCs having SEQ ID NO: 39 or 9 andtwo LCs having SEQ ID: 8, and wherein preferably in each HC the glutamine (X1 of SEQ ID NO: 39 and Q at position 1 of SEQ ID NO: 9, respectively) at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7of SEQ ID NO: 39 and K at position 450 of SEQ ID NO: 9) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300 (XV of SEQ ID NO. 39 and N at position 300 of SEQID NO: 9), wherein the amino acids at position X2, X3, X4, and X5are either modified orunmodified, preferably unmodified or wherein the methionine at position M255 of SEQ ID NO:9 is not oxidized, the asparagine at positions N318 and N387 of SEQ ID NO: 9 is not deamidated and does not comprise a succinimide, and the proline at position P448 of SEQ ID NO: 9 is not amidated, wherein the glycine (X6 of SEQ ID NO: 39 and G at position 449 of SEQ ID NO: 9)is present and not clipped off, and wherein the amino acids at positions XI, XII, XIII, XIV, XVI,XVI of SEQ ID NO: 39 are either modified or unmodified, preferably unmodified or whereinthe methionine at positions M71, M115, M361, and M431 of SEQ ID NO: 9 is not oxidized, the asparagine at position N58 of SEQ ID NO: 9 is not deamidated and the aspartate at positionD283 of SEQ ID NO: 9 is not isomerized. In an alternative embodiment, the antibody iscomposed of two heavy chains having SEQ ID NO: 9, and two light chains having SEQ ID: 8, and wherein preferably in the heavy chain the glutamine at the N-terminus is modified as pyro- glutamic acid, the C-terminal lysine is cleaved or absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300. In a preferred embodiment, the composition comprises one or more antibodies as defined hereinbefore, i.e., the composition comprises one or more antibodies in which the lysine (K) at position 450 of SEQ ID NO: 9 is absent, preferably wherein in more than 90%, preferably in about 95% to 100%, preferably in about 95% to 96% of the antibodies the lysine (K) at position 450 of SEQ ID NO: 9 is absent and which comprise a pyro-glutamic acid at the N-terminal of the heavy chain sequence instead of glutamine, preferably wherein in more than 90%, preferably in about 99% to 100% of the antibodies the glutamine (Q) at position 1 of SEQ ID NO: 9 is modified to pyroglutamate. In a preferred embodiment, the asparagine residues (N) at positions 58, 318, and 387 in the one or more antibodies are not deaminated and do not comprise a succinimide and the composition does comprise no antibodies or only a low amount of antibodies, for example less than about 10%, preferably 5% of the antibodies, in which the asparagine residues (N) at positions 58, 318, and / or 387 are deamidated, respectively. In a further preferred embodiment, the methionine residues at positions 71, 115, 255, 361 and 431 in the one or more antibodies are not oxidized and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the methionine residues at positions 71, 115, 255, 361 and / or 431 are oxidized. In a further preferred embodiment, the aspartate at position 283 in the one or more antibodies is not isomerized and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the aspartate at position 283 is isomerized, respectively. In a further preferred embodiment, the glycine at position 449 in the one or more antibodies is not absent, i.e., the glycine is present and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the glycine at position 449 is absent, respectively, i.e., the composition mainly comprises antibodies in which the glycine is present. Consequently, preferably, the proline at position 448 in the one or more antibodies is not amidated and the composition comprises no antibodies or only a low amount of antibodies, for example less than about 5% of the antibodies, in which the proline at position 448 is amidated. In a preferred embodiment, the composition is an aqueous composition, also referred to as liquid formulation and thus, also comprises water for injection. As illustrated in Example 4, several stability tests that have been performed with theformulation / pharmaceutical compositions of the present disclosure demonstrate that theantibody remains stable under various conditions, e.g., at 40 ± 2 °C and 75 ± 5% relative humidity (RH) for at least 1 month (stress stability studies); at 25 ± 2 °C / 60 ± 5% RH for at least 6 months (accelerated stability studies); and at 5 ± 3 °C for at least 12 months to 18 months (long-term stability studies). Furthermore, a shelf-life of 24 months at 2-8°C when protected from light has been determined for the antibody formulation.Accordingly, in one embodiment, the composition can be characterized by the antibodyremaining stable at 40 ± 2 °C and 75 ± 5% RH for at least 1 week, preferably for at least up to1 month; at 25 ± 2 °C / 60 ± 5% RH for at least 1 month, and preferably for at least up to 6months; and / or at 5 ± 3 °C for at least 1 month, and preferably for at least up to 12 months,more preferably for at least up to 18 months. In one embodiment, the pharmaceuticalcomposition has a shelf-life of 24 months at 2-8°C when protected from light.The stability of the formulation may be at least partially attributed to the antibody’s constantregion and more particularly, to the PTMs present in in the heavy chain of the antibody of thepresent disclosure as defined hereinbefore. In accordance with the present disclosure, pharmaceutical formulations, essentially characterized by a pH 5.3 to 6.3, preferably pH 5.8±0.1, typically comprising a histidine buffer and as excipients sucrose, polysorbate, preferably polysorbate 80, and water for infusion / injection have been developed for a recombinant human monoclonal antibody specific for the disease associated amyloidogenic form of TTR, featuring ALXN2220, also known as NI006, at a concentration of about 25 mg / ml to about 150 mg / ml, typically at about 50 mg / ml. As mentioned, a formulation of the antibody at 50 mg / ml in 20 mM histidine, 6.5% or 8% (w / v) sucrose, and 0.03 % (w / v) PS80 at pH 5.8, was identified in the Examples as the lead candidatefor further development and indeed, a formulation of the antibody at 50 mg / ml in 20 mMhistidine, 8% (w / v) sucrose, and 0.03 % (w / v) PS80 at pH 5.8 has been successfully used inclinical trials, and thus, represents the most preferred embodiment of the present disclosure aswell as equivalent formulations maintaining the physicochemical properties that are critical forthe stability and function of the antibody as tested and validated in the appended Example 4.To make changes in the concentration of components and / or substitute excipients in the preferred formulation, one should consider the following factors to ensure the stability and efficacy of the antibody: Histidine: acts as a buffer agent. The buffer capacity is related to the ability of histidine to maintain the pH near its pKa value. Since the pKa of histidine is approximately 6.0, at pH 5.8, it is slightly less efficient but still functional as a buffer. The buffer capacity is also influenced by the concentration of the buffering agent and the proximity of the pH to the pKa. Sucrose: stabilizes proteins during freeze / thaw cycles and adds osmolality. Sucrose contributes significantly to the osmolality of the solution, which is important for maintaining the structural IgG antibody. The protein of interest at a high concentration: antibodies, like all proteins, have buffering capacity due to the presence of ionizable groups in their amino acid side chains. These groups include the carboxyl groups of aspartic acid and glutamic acid, the amino groups of lysine and arginine, the imidazole group of histidine, the hydroxyl group of tyrosine, the thiol group of cysteine, and the terminal amino and carboxyl groups.The composition of the present disclosure which comprises the above-referenced formulationfulfills at least the acceptance criteria as referred to in Tables 25 and 26 (which can also be usedto determine whether a composition / formulation with changed concentration of componentsand / or substituted excipients are still long-term stable), Preferably, the composition of thepresent disclosure has a content of acidic species of the antibodies of ≤ 40.0% and of basic species of the antibodies of ≤ 15.0% after 6 months storage at 5 ± 3 °C as determined by iCIEF;and / or has a content of high molecular weight species of ≤ 5.0% after 6 months storage at 5 ±3 °C as determined by SEC-HPLC. During the manufacturing process of ALXN2220, as described in detail in Example 3, it has been shown that reducing the pH dead band from 0.20 to 0.05 led to considerable reduction in acidic species, e.g., from about 37% to about 29%. Accordingly, in one embodiment, the amount of acidic species in the composition of the present disclosure is about 30%, preferably between 25% and 33%, more preferably between 25% and 32%. It has been further shown that the charged variant profile has varied in general. Thus, in a further preferred embodiment, the amount of acidic species in the composition of the present disclosure is equal or less than about 32%, and preferably the amount of basic species is equal to or less than about 5%, and the amount of neutral species is equal to or higher than about 63%. Embodiments of the disclosure relate to methods for the production of an antibody comprising an immunoglobulin heavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8, comprising (a) culturing a host cell, e.g., Chinese Hamster Ovary K1 (CHO-K1) cell, comprising one or more expression vectors or vector systems comprising the polynucleotides encoding the antibody HC and the LC under conditions sufficient for the expression of theantibody in the culture; (b) setting a pH setpoint and pH dead band of the culture to adjust levelof acidic, basic, and / or neutral antibody species in the culture; and (c) isolating the antibodyHC and LC from the cell culture; and (d) optionally formulating the isolated antibody into apharmaceutical formulation comprising the isolated antibody and a pharmaceuticallyacceptable carrier. In specific embodiment, the disclosure relate to methods for the production of an antibody comprising an immunoglobulin heavy chain (HC) having the amino acid sequence of SEQ IDNO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8, comprising (a) culturing a host cell, e.g., Chinese Hamster Ovary K1 (CHO-K1) cell, comprising one or more expression vectors or vector systems comprising the polynucleotides encoding the antibody HC and the LC under conditions sufficient for the expression of the antibody in the culture; (b) setting a pH setpoint and pH dead band of the culture to adjust level of acidic, basic, and / or neutral antibody species in the culture; and (c) isolating the antibodyHC and LC from the cell culture; and (d) optionally formulating the isolated antibody into apharmaceutical formulation comprising the isolated antibody and a pharmaceutically acceptable carrier, wherein step (b) comprises setting a pH setpoint of about 6.90 and a pHdeadband between 0.05 to 0.10 to reduce level of acidic antibody species; preferably the pHdeadband is set to about 0.05.In some embodiments, implementation of step (b) comprising setting the pH and pH deadbandreduces the level of acidic species in cultured antibody preparation while also reducing levelsof mannose 5 content. In some embodiments, implementation of step (b) comprising setting the pH at 6.90 and pHdeadband between 0.05 and 0.10; preferably a pH at 6.90 and pH deadband of about 0.05,reduces levels of N-linked mannose-5 glycan (Man5) in the antibody preparation compared toa production method wherein step (b) is implemented at pH 6.90 and pH deadband of 0.20. Insuch embodiments, a reduction in Man5 levels is greater than >20%; more preferably thereduction in Man5 levels is about 40%-50% compared to levels of Man5 in an antibodypreparation produced using an identical method except step (b) is implemented at pH 6.90 andpH deadband of 0.20.In some embodiments, implementation of step (b) comprising setting the pH at 6.90 and pHdeadband between 0.05 and 0.10; preferably pH at 6.90 and pH deadband of about 0.05; isimplemented in the production phase comprising day 5 to day 14 of the culture process, e.g., between day 5 to day 14 post-seeding of the CHO-K1 cells. In some embodiments, implementation of step (b) comprising setting the pH at 6.90 and pHdeadband between 0.05 and 0.10; preferably pH at 6.90 and pH deadband of about 0.05, controlshigh mannose species in the antibody preparation, without concomitantly and adversely impact on secondary quality attributes of the antibody preparation, e.g., wherein secondary quality attributes are selected from (1) relative levels (in %) of main vs. high molecular weight (HMW) vs. low molecular weight (LMW) antibody species in the preparation, e.g., as determined by size exclusion chromatography (SEC); (2) relative levels (in %) of main antibody species in the preparation, e.g., as determined using capillary electrophoresis sodium dodecyl sulfate under non-reduced conditions (CE-SDS-NR); and / or (3) relative levels (in %) of antibody heavy and light chains in the preparation, e.g., as determined using capillary electrophoresis sodium dodecyl sulfate under reduced conditions (CE-SDS R).Embodiments of the disclosure relate to antibodies produced according the above methods, e.g.,antibodies comprising an immunoglobulin heavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8, produced using a method comprising (a) culturing a host cell, e.g., Chinese Hamster Ovary K1 (CHO-K1) cell, comprising one or more expression vectors or vector systems comprising the polynucleotides encoding the antibody HC and the LC under conditions sufficient for the expression of the antibody in the culture; (b) setting a pH setpoint and pH dead band of the culture to adjust level of acidic, basic, and / or neutral antibody species in the culture,preferably wherein the adjustment comprises reduction of acidic species of the antibody cultureby setting the pH at 6.90 and pH deadband between 0.05 and 0.10, preferably setting a pH deadband about 0.05; and (c) isolating the antibody HC and LC from the cell culture; and (d) optionally formulating the isolated antibody into a pharmaceutical formulation comprising the isolated antibody and a pharmaceutically acceptable carrier.The pH dead band is in embodiments set to less than 0.2, preferably of ≤ 0.19, preferably of ≤0.18, preferably of ≤ 0.175, preferably of ≤ 0.17, preferably of ≤ 0.16, preferably of ≤ 0.15, preferably of ≤ 0.14, preferably of ≤ 0.13, preferably of ≤ 0.125, preferably of ≤ 0.12, preferably of ≤ 0.11, preferably of ≤ 0.1, preferably of ≤ 0.09, preferably of ≤ 0.08, preferably of ≤ 0.075, preferably of ≤ 0.07, preferably of ≤ 0.06, most preferably of ≤ 0.05. In preferred embodiments, the pH dead band is set to about 0.1-0.05, preferably to 0.05 or 0.1, and most preferably to 0.05. In embodiments, the antibodies of the disclosure are formulated, e.g., as high concentrationpharmaceutical compositions for administration into a patient, at pH 5.8. The pH is slightlybelow the pKa of histidine, which will still provide a buffering effect. For example, if theoriginal buffer system has a concentration of 20 mM histidine and the pH is 5.8, one could calculate the ratio of the conjugate base to the acid using the Henderson-Hasselbalch equation. To maintain the pH, one could double both the concentration of the protonated form (HA) and the deprotonated form (A-) to 40 mM. Since changing the total concentration of the buffer will affect the ionic strength and osmolality of the solution, which can have effects on the stability and solubility of proteins, the concentration and / or nature of the osmolality agent, here sucrose, may be adjusted, and the corresponding formulation tested in accordance with the Example.As mentioned above, the heavy and light chain complementarity determining regions(VHCDRs and VLCDRs), including the heavy and light antigen-binding domains ofNI006 / ALXN2220 has been described in WO 2015 / 092077 A1 (designated as antibody NI- 301.37F1) and in Michalon et al., Nat. Commun. 12 (2021), 3142 (designated as antibody NI301A). As disclosed in WO 2015 / 092077 A1, NI006 (NI-301.37F1) is inter alia characterized by binding to aggregated human wild-type transthyretin (wtATTR), which is shown in Figures 2 to 4 and 7 and described in Examples 3 to 6, and further described at page 46, last paragraph. In addition, WO 2015 / 092077 A1 discloses that NI006 (NI-301.37F1) does not bind to monomers and dimers of the human native transthyretin (TTR) as shown in Example 5 and Figure 4. This binding profile is advantageous since the antibody binds selectively toaggregated wtTTR and thus allows prima facie to consider not only the treatment of hereditarytransthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy, FAP), which is due to mutations in the gene encoding TTR, but also the treatment of wild-type transthyretin amyloidosis (wtATTR), known as senile systemic amyloidosis (SSA). Moreover, the antibody is not at risk of interfering with native monomer assembly into physiological tetramers. In addition, the antibody has been shown to removeATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivofrom mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion,wherein biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages; see Michalon et al., Nat. Commun.12 (2021), 3142.Thus, the present disclosure relates to a composition, preferably a pharmaceutical composition,comprising the antibody of the present disclosure as defined hereinbefore at a concentration ofabout 50 mg / ml to about 100 mg / ml, preferably at a concentration of about 50 mg / mL or 100 mg / mL, preferably of about 50 mg / mL in an aqueous formulation further comprising L- histidine (L-histidine and L-histidine monohydrochloride), sucrose, polysorbate 80, and waterfor injection for use in a method of treating TTR amyloidosis (ATTR) in a subject. Preferably,the composition is the composition of the present disclosure, i.e., the composition comprisingthe antibodies of the present disclosure at a concentration of about 50 mg / ml to about 100mg / ml, preferably at a concentration of about 50 mg / mL or 100 mg / mL, preferably of about 50 mg / mL in an aqueous formulation further comprising L-histidine (L-histidine and L-histidine monohydrochloride), sucrose, polysorbate 80, and water for injection for use in a method of treating TTR amyloidosis (ATTR) in a subject.In a preferred embodiment, the formulation of the composition of the present disclosure and thecomposition for use in accordance with the present disclosure, respectively, has a pH of 5.8.Furthermore, preferably, the formulation of the composition of the present disclosure and thecomposition for use in accordance with the present disclosure, respectively, has as an osmolality of ≥ 240 mOsm / Kg. Furthermore, as mentioned above, the formulation of the composition is stable and thus, in one embodiment, the pharmaceutical composition for use in accordance with the present disclosure has a shelf-life of 24 months at 2-8°C and protected from light and shows preferably the above- mentioned stability criteria.In one embodiment, the composition of the present disclosure and the composing for use inaccordance with the present disclosure comprises a formulation, which when added up to about2 ml essentially consists of: 50 mg or 100 mg of the antibody, 2.12 mg L-Histidine, 5.56 mg L-Histidine monohydrochloride 160 mg sucrose, 0.6 mg PS80, and water for injection. The corresponding amounts of the antibody and the excipients can be calculated in case it is intended to provide a formulation of another volume, for example 2.25 ml, 20 ml, or 22.5 ml. As referred to in Example 1, antibody NI006 / ALXN2220 can be produced in Chinese hamster ovary (CHO) cells. CHO cells are the most widely used mammalian cells for the production of recombinant monoclonal antibodies due to their ability to perform post-translational modifications (PTMs) on the antibody molecules, which typically take place in the human body as well. Through genetic manipulation by mutagenesis, different CHO daughter cells with improved qualities have been established. Among those variants are CHO-K1, CHO-S, CHO- DXB11 and CHO-DG44. Thus, in one embodiment, the antibody used in the composition ofthe present disclosure and in the composition for use in accordance with the present disclosure,respectively, is produced in CHO cells, preferably in CHO-K1 cells and is purified from the cell culture medium for further use. Furthermore, the compatibility of the antibody formulation with clinical in-use materials was evaluated. In particular, the compatibility with polyvinyl chloride IV bag, IV line, and filter as well as with polyvinyl chloride syringe and corresponding non-polyvinyl chloride materials were assessed when using glucose or saline as diluent. Three concentrations 1 mg / mL, 20mg / mL, and 50 mg / mL were assessed, and the data provided in Example 4 indicate that theformulation is in general compatible with the clinical in-use materials evaluated. In particular, in the saline group, visible particles were observed, indicating that NI006 / ALXN2220 is less stable in saline, wherein the data show that when diluted in a glucose solution, no substantial changes in the appearance, protein concentration, sub-visible particle, SEC-HPLC, and ELISA binding assay were observed. Thus, NI006 / ALXN2220 at concentrations of 1.0 mg / mL, 20.0mg / mL, and 50.0 mg / mL was shown to be stable at 2 - 8 °C for 24 hours followed by 25 °C for6 hours (30 hours in total) and being compatible with the clinical in-use materials evaluated. The most common route for the administration of monoclonal antibodies in therapy is intravenous (IV) infusion. This method is preferred because it allows the antibody to bedelivered directly into the bloodstream, ensuring immediate distribution throughout the bodyand enabling precise dosing. Intravenous administration is particularly important for monoclonal antibodies due to their large molecular size, which generally prevents them from being effectively absorbed through the gut or skin. This means that oral or transdermal delivery methods are not suitable for these types of drugs. Additionally, IV administration bypasses the first-pass metabolism in the liver, which can significantly alter the drug's efficacy and safety profile.Therefore, the composition of the present disclosure and the composition for use in accordancewith the present disclosure, respectively has been particularly developed for IV administrationand is thus, preferably the formulation suitable for intravenous administration.In some embodiments, the composition of the present disclosure and the composition for use inaccordance with the present disclosure, respectively has not been reconstituted from a lyophilized anti-TTR antibody or antigen-binding fragment thereof and / or is not further lyophilized.Since in the composition of the present disclosure and the composition for use in accordancewith the present disclosure, respectively, sucrose is used as tonicity modifier and additionalstabilizer of the antibody in the formulation, there is no need for NaCl, especially if the primarypurpose of NaCl is to stabilize the protein, which sucrose can accomplish without increasing the ionic strength of the solution, Therefore, the pharmaceutical composition of the presentdisclosure is preferably essentially free of sodium chloride.In addition, or alternatively, the composition of the present disclosure and the composition foruse in accordance with the present disclosure, respectively, is essentially free of (or, e.g., completely lacks) a poloxamer.The formulation of the composition of the present disclosure and the composition for use inaccordance with the present disclosure, respectively, is preferably provided in vials. While in a preferred embodiment, the formulation, is provided in 2 ml glass vials, preferably type I clear glass vials, preferably with a 12.5% overfill (2.25 ml), other pharmaceutical containers with different fill volumes are also encompassed by the disclosure, for example 20 ml vials, e.g., 20 ml glass vials, preferably with a 12.5% overfill (22.5 ml), or other container / vials which aredesigned such that the vials / container and amount of antibody provided, respectively, add up tothe flat doses, optionally plus about 12.5%, provided for example by the overfill.In a preferred embodiment, the formulation is provided in 2 mL glass vial with an aluminumflip-off seals over a rubber stopper, to which preferably a volume of 2.25 ml is added.In a preferred embodiment, formulation of the composition of the present disclosure and thecomposition for use in accordance with the present disclosure, respectively, is a preservative- free concentrate for solution for infusion that is presented as sterile, colorless to slightly yellow, clear to slightly opalescent liquid, essentially free of visible particles, wherein preferably theconcentrate for solution is diluted in sterile glucose before administration, as an intravenousinfusion.The present disclosure further relates to corresponding pharmaceutical containers comprisingthe composition / formulation of the present disclosure.The present disclosure further relates to a stable aqueous formulation for use in a method oftreating TTR amyloid cardiomyopathy (ATTR-CM), wherein the formulation(i) essentially consists of:(a) the antibody of the present disclosure, preferablythe antibody is composed of two HCs having SEQ ID NO: 7 or 9 and two LCs having SEQ ID: 8, and wherein preferably in each HC the glutamine (X1of SEQ ID NO: 7 and Q at position 1 of SEQ ID NO: 9, respectively) at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7 of SEQ ID NO: 7 and K at position 450 of SEQ ID NO: 9) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300 of SEQ ID NO: 9, wherein the amino acids at position X2, X3, X4, and X5 of SEQ ID NO: 7 are either modified or unmodified, preferably unmodified or wherein the methionine at position M255 of SEQ ID NO: 9 is not oxidized, the asparagine at positions N318 and N387 of SEQ ID NO: 9 is not deamidated and does not comprise a succinimide, and the proline at position P448 of SEQ ID NO: 9 is not amidated, and wherein the glycine (X6 of SEQ ID NO: 7 and G at position 449 of SEQ ID NO: 9) is preferably present and notclipped off. In one preferred embodiment, the antibody is composed of two HCs having SEQ ID NO: 39 or 9 and two LCs having SEQ ID: 8, and wherein preferably in each HC the glutamine (X1of SEQ ID NO: 39 and Q at position 1 of SEQ ID NO: 9, respectively) at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7 of SEQ ID NO: 39 and K at position 450 of SEQ ID NO: 9) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300 (XVof SEQ ID NO. 39 and N at position 300 of SEQ ID NO: 9), wherein the amino acids at position X2, X3, X4, and X5 are either modified or unmodified, preferably unmodified or wherein the methionine at position M255 of SEQ ID NO: 9 is not oxidized, the asparagine at positions N318 and N387 of SEQ ID NO: 9 is not deamidated and does not comprise a succinimide, and the proline at position P448 of SEQ ID NO: 9 is not amidated, wherein the glycine (X6 of SEQ ID NO: 39 and G at position 449 of SEQ ID NO: 9) is preferably present and not clipped off, and wherein the amino acids at positions XI, XII, XIII, XIV, XVI, XVIof SEQ ID NO: 39 are either modified or unmodified, preferably unmodified or wherein the methionine at positions M71, M115, M361, and M431 of SEQ ID NO: 9 is not oxidized, the asparagine at position N58 of SEQ ID NO: 9 is not deamidated and the aspartate at position D283 of SEQ ID NO: 9 is not isomerized; alternatively, theantibody is composed of two heavy chains having SEQ ID NO: 9, and two light chains having SEQ ID: 8, and wherein preferably in the heavy chain the glutamine at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine is cleaved or absent, and the heavy chain is N-glycosylated, preferably wherein the N- glycosylation site is at position Asn300, (b) histidine at a concentration of about 20 mM,(c) sucrose at a concentration of about 8% (w / v),(d) PS80 at a concentration of about 0.03% w / v,(e) water for injections,(ii) has a pH of about 5.8;(iii) is contained in a 2 mL single use vial comprising about 100 mg of antibody or in a 20 mLsingle use vial comprising 1000 mg of antibody:(iv) is diluted prior to administration with a sterile glucose solution, preferably to aconcentration of not lower than 1 mg / mL antibody; and(v) is administered by intravenous infusion.The present disclosure further relates to a kit comprising one or more containers of the presentdisclosure and means for delivering the formulation / composition to a human subject, optionallywherein the means comprise an infusion bag or a syringe. In a preferred embodiment, theformulation is a preservative-free, clear to opalescent and colorless to pale yellow solution, provided as 100 mg / 2 mL in a vial.The present disclosure further relates to an article of manufacture comprising one or morecontainer(s) of the present disclosure, and a label, wherein the label prescribes that the antibody is indicated for the treatment of ATTR, especially ATTR cardiomyopathy (ATTR-CM), e.g., due to wild-type or hereditary transthyretin-mediated amyloid cardiomyopathy (wtATTR-CM or hATTR-CM). In preferred embodiment, the kit comprises a leaflet prescribing that the antibody is to be administered intravenously, which may contain, e.g., instructions for IVdosing. In a preferred embodiment, the container(s) are glass vials as defined hereinbefore.In a further preferred embodiment, the kits may further comprise a diluent. In embodiments,the diluent comprises a 5 % glucose solution, wherein the glucose solution can be provided ina further container. In a preferred embodiment, the formulation of the antibody is a preservative- free, clear to opalescent and colorless to pale yellow solution, provided as 100 mg / 2 mL in a vial.The present disclosure further relates to a method of treating ATTR, preferably ATTRcardiomyopathy (ATTR-CM) and / or ATTR polyneuropathy (ATTR-PN), wherein the method comprises administering the antibody and the composition, respectively, of the presentdisclosure to a subject in need thereof, preferably wherein administration is performedintravenously. Preferably, the antibody / composition is diluted and administered as an intravenous infusion over approximately one to two hours, wherein dilution is preferably performed in 5% glucose solution.In some embodiments, the patient to be treated with the antibodies of the present disclosure orpharmaceutical compositions comprising the same have been pre-screened, e.g., foridentification that they have wtATTR-CM or hATTR-CM and the treatment is provided selectively to such patients who have been positively identified. In some embodiments, the subject has been previously treated with and / or is concurrentlyreceiving a disease modifying agent, for example a TTR tetramer stabilizer like tafamidis(VYNDAQEL® or VYNDAMAX®), or Acoramidis (AG10). Presently, tafamidis, oral disease-modifying treatment acting, is the only approved pharmacologic treatment specifically targeting ATTR-CM, both wild-type and hereditary forms.The present disclosure further provides a method for manufacturing the antibody of the presentdisclosure and a corresponding drug product, respectively.The method of producing the antibody or an antigen-binding fragment thereof comprises a) cloning the nucleic acid molecule and the polynucleotide, respectively, of the present disclosure which comprises the first nucleotide sequence and preferably the nucleotidesequence of the first signal peptide into an expression vector, and cloning the nucleicacid molecule and the polynucleotide, respectively, of the present disclosure whichcomprises the second nucleotide sequence and preferably the nucleotide sequence of the second signal peptide into an expression vector, wherein the first and the second nucleotide sequences may be provided in the same or different expression vectors, preferably in different expression vectors; b) transforming the expression vector(s) into a non-human host cell, preferably into a CHO cells, more preferably CHO-K1 cells; c) culturing the host cell under conditions allowing for the expression of the immunoglobulin chains comprising heavy chain and light chain; andd) isolating the immunoglobulin chains and resultant IgG antibody, respectively, from the culture and optionally digesting the IgG antibody to generate antigen-binding fragments of the antibody, e.g., using enzymatic digestion comprising papain cleavage to generate Fab fragments. In embodiment, the method of the present disclosure comprises cultivation of the host cell, inparticular the CHO-K1 cells with a pH dead band of less than 0.2, preferably of ≤ 0.19,preferably of ≤ 0.18, preferably of ≤ 0.175, preferably of ≤ 0.17, preferably of ≤ 0.16, preferably of ≤ 0.15, preferably of ≤ 0.14, preferably of ≤ 0.13, preferably of ≤ 0.125, preferably of ≤ 0.12, preferably of ≤ 0.11, preferably of ≤ 0.1, preferably of ≤ 0.09, preferably of ≤ 0.08, preferably of ≤ 0.075, preferably of ≤ 0.07, preferably of ≤ 0.06, most preferably of ≤ 0.05. In preferred embodiments, the pH dead band is set to about 0.1-0.05, preferably to 0.05 or 0.1, and mostpreferably to 0.05. Preferably, the method of the present disclosure comprises cultivation of thehost cell, in particular the CHO-K1 cells at pH 6.9 with a pH dead band of less than 0.2, preferably of ≤ 0.19, preferably of ≤ 0.18, preferably of ≤ 0.175, preferably of ≤ 0.17, preferably of ≤ 0.16, preferably of ≤ 0.15, preferably of ≤ 0.14, preferably of ≤ 0.13, preferably of ≤ 0.125, preferably of ≤ 0.12, preferably of ≤ 0.11, preferably of ≤ 0.1, preferably of ≤ 0.09, preferably of ≤ 0.08, preferably of ≤ 0.075, preferably of ≤ 0.07, preferably of ≤ 0.06, most preferably of ≤ 0.05. In preferred embodiments, the pH dead band is set to about 0.1-0.05, preferably to 0.05or 0.1, and most preferably to 0.05. In embodiment, the pH is set to pH 6.9 with the aboveindicated pH dead band. The method may be further used to produce the pharmaceutical composition of the presentdisclosure and the corresponding drug product. In particular, after producing the antibody, themethod further comprises e) formulating the antibody in an aqueous solution comprising the antibody at a concentration of about 50 mg / ml or about 100 mg / ml and histidine at a concentration of about 20 mM, sucrose at a concentration of about 6.5% weight per volume (w / v) or about 8% (w / v) sucrose, and PS80 at a concentration of about 0.03% w / v, wherein the formulation has a pH of about 5.8 to generate a pharmaceutical composition comprising the antibody; and optionallyf) filing the composition into a vial, and further optionallyg) packing the pharmaceutical composition and vial, respectively, in a kit together with instructions for administration of the antibody, e.g., intravenously in a human patient.As mentioned above, the antibody of the present invention has been shown to remove ATTRdeposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo frommice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion, whereinthe biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages; see Michalon et al., Nat. Commun.12 (2021), 3142. To further study the mechanisms of macrophage mediated amyloid depletion, a high-resolution live-cell imaging assay has been developed. This assay includes the incubation of cardiac tissue sections that comprise ATTR with THP-1 derived macrophages in the presence of the anti-TTRantibody and subsequent live-cell imaging.In one approach, the method includes the staining of amyloid deposits in the tissue sectionswith the amyloid specific red fluorescent dye Amytracker 680 and the labelling ALXN2220with the green fluorescent dye Vivotag-680. After incubation of the stained tissue sections withthe macrophages in the presence of labelled ALXN2220, high-resolution live-cell imaging was performed as described in Example 5. The overlap of the fluorescent images visualizing either the red fluorescent dye used for staining the amyloid deposits or the green fluorescent dye with which the antibody was labelled showed that the same parts of the tissue were stained with the red fluorescent dye directly staining the amyloid deposits and with the green fluorescent dye staining the amyloid deposits via binding of the labelled antibody to the amyloid deposits; see Fig.7. Thus, binding of the antibody to the ATTR in the tissue sections was confirmed.In another approach, the method includes the staining of amyloid deposits in the tissue sectionswith the amyloid specific red fluorescent dye Amytracker 680. ALXN2220 was not labelled.After incubation of the stained tissue sections with the macrophages in the presence of the antibody, high-resolution live-cell imaging was performed as described in Example 5. As shown in Fig. 8, ALXN2220 triggered amyloid phagocytosis by macrophages. The punctate and intracellular red fluorescence pattern revealed the presence of ATTR amyloid in phagocyticvesicles and thus, showed macrophage mediated ATTR internalization.In a further approach, the method includes labelling of ALXN2220 with the green fluorescent dye Vivotag-680. After incubation of the unstained tissue sections with the macrophages in the presence of the labelled antibody, high-resolution live-cell imaging was performed as describedin Example 5 and the fluorescent signal visible in Fig. 9 and 10 represents amyloid staining dueto the antibody binding to ATTR. As shown in Fig. 9 and 10, either punctuate fluorescencesignals separated from the fluorescence signal of the amyloid over time, or a thin and elongatedfluorescence signal as well as punctuate fluorescence signals separated from the adjacentcardiomyocytes indicting macrophage mediated amyloid fragmentation and separation ofATTR deposits form the adjacent cardiomyocytes followed by amyloid fragmentation.Accordingly, it was shown for the first time that life-cell imaging is a suitable method for detecting antibody binding to amyloid deposits and for visualizing the removal of amyloid deposits via activation of phagocytic macrophages. These findings opened the possibility todevelop methods for screening and validation of anti-amyloid antibodies and further amyloiddepleting compounds using live-cell imaging.Accordingly, the present invention relates in one aspect to a method of validating an amyloiddepleting drug, also referred to as amyloid depleting compound, comprising incubating tissuesections comprising amyloid deposits with macrophages in the presence of the amyloiddepleting drug, wherein the tissue sections are stained with an amyloid specific fluorescent dyeand / or the amyloid depleting drug is labeled with a fluorescent dye, and performing high-resolution live-cell imaging, wherein (a) an overlap of the antibody fluorescence signal and the amyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocytic vesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from the fluorescence signal of the amyloid indicates macrophagemediated amyloid fragmentation. Thus, the live-cell imaging can be used to visualize bindingof the amyloid depleting drug to the amyloid deposits, macrophage mediated internalization ofamyloid, and macrophage mediated amyloid fragmentation, wherein these mechanisms led tointracellular amyloid degradation. Accordingly, if any one of (a) to (c), preferably all of (a) to(c), more preferably at least any one of (b) and (c), or (b) and (c) is / are observed during live-cell imaging, it is verified that the amyloid depleting drug has indeed amyloid depleting activity.To confirm that the results are specific, i.e. attributed to the activity of the amyloid depletingdrug, the observed mechanisms (binding of the amyloid depleting drug to the amyloid deposits, macrophage mediated internalization of amyloid, and macrophage mediated amyloid fragmentation) should not be observed when the tissue sections having amyloid deposits and macrophages are not incubated in the presence of the amyloid depleting drug, but for examplein the presence of a control compound. The control compound belongs preferably to the sameclass of substances as the amyloid depleting drug, and preferably in the same substance class as antibodies, but shows unspecific binding. Same regards to the methods described further below.In another aspect, the present invention relates to a screening method for identifying andoptionally obtaining an amyloid depleting drug from a plurality of test compounds comprisingincubating tissue sections having amyloid deposits with macrophages in the presence of the testcompound, wherein the tissue sections are stained with an amyloid specific fluorescent dyeand / or the test compound is labeled with a fluorescent dye, and performing high-resolution live-cell imaging, wherein (a) an overlap of the test compound fluorescence signal and the amyloidfluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocytic vesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from the fluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation, wherein the presence of any one of items (a) to (c), preferablyof all of (a) to (c), or at least any one of (b) and (c), preferably (b) and (c) indicates the suitabilityof the test compound as amyloid depleting drug. The present invention further relates to a method of screening of an amyloid depleting drug for its capability to bind to amyloid, and to mediate macrophage recruitment to amyloid deposits, followed by amyloid fragmentation and internalization, i.e., for its capability to activate macrophage mediated amyloid fragmentation and internalization, leading to intracellular degradation of amyloid, wherein the method comprises incubating tissue sections comprising amyloid deposits with macrophages in the presence of the amyloid depleting drug, wherein the tissue sections are stained with an amyloid specific fluorescent dye and / or the amyloid depletingdrug is labeled with a fluorescent dye, and performing high-resolution live-cell imaging,wherein (a) an overlap of the antibody fluorescence signal and the amyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocytic vesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from the fluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation. In one embodiment, the methods of the present invention comprise the testing of a control sample, e.g.., the tissue sections are incubated with macrophages in the presence of a control. In order to be qualified as amyloid depleting drug, the test substance used for the method of screening should have a an enhanced binding of the amyloid depleting drug to the amyloid, an enhanced internalization of amyloid, and / or an enhanced amyloid fragmentation in comparisonto the control and / or in order to be suitable in the treatment of an amyloidosis or amyloid-relateddisease, the amyloid depleting drug should have a an enhanced binding of the amyloid depleting drug to the amyloid, an enhanced internalization of amyloid, and / or an enhanced amyloidfragmentation in comparison to the control. The control sample can be any control showingunspecific binding to the amyloid and / or the macrophages.The present invention also relates to a method of producing a pharmaceutical composition ofan amyloid depleting drug comprising (i) providing, optionally producing the amyloid depletingdrug; (ii) subjecting the amyloid depleting drug to the method as defined hereinbefore; (iii)using the information obtained in step (ii) as part of an assessment of whether the amyloiddepleting drug may be used as a pharmaceutical composition or not; and optionally formulatingthe amyloid depleting drug found to be useful as a pharmaceutical composition in step (iii) with a pharmaceutically acceptable carrier, such as a buffer, a tonicity agent and / or a surfactant, most preferably all three components. In another aspect, the present invention relates to a method for characterization, validation, development and / or quality control, for example batch control of an amyloid depleting drugcomprising (i) providing, optionally producing the amyloid depleting drug; (ii) subjecting theamyloid depleting drug to the method as described hereinbefore; (iii) communicating theinformation obtained in (i) to a client, contracting party or cooperation partner and / or selectingthe drug that has been determined to be a suitable amyloid depleting drug; and optionally (iv)using the amyloid depleting drug or a pharmaceutical composition comprising the amyloid depleting drug for the treatment of an amyloidosis or amyloid-related disease. Combination therapies are also of interest for the treatment of amyloidosis. For example, as disclosed in WO 2021 / 228987 A1, the combination of an anti-TTR antibody as amyloid depleting drug with a TTR tetramer stabilizer, such as tafamidis and diflunisal, or with a TTR gene silencer is a promising approach for the treatment of TTR amyloidosis. During the development of combination therapies, the impact of the drugs on each other must be carefully tested to avoid unwanted effects, like lowering of treatment efficiency. Accordingly, the presentinvention also refers to a method of analyzing the impact of an agent, for example a seconddrug, a tracer, radiation, a label, preferably wherein the agent is a second drug, and in particulara second drug for the treatment of an amyloidosis or amyloid-related disease or a pain killer,e.g., a non-steroidal anti-inflammatory drug such as ibuprofen, or paracetamol, on the amyloiddepleting activity of the amyloid depleting drug comprising incubating tissue sections havingamyloid deposits with macrophages, preferably THP-1 derived macrophages, in the presence of the amyloid depleting drug and the agent; and performing high-resolution live-cell imaging, where (a) an overlap of the antibody fluorescence signal and the amyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocytic vesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from the fluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation, wherein, compared to a control, which is preferably a tissue section having amyloid deposits being incubated with macrophages and the amyloid depleting drug without the agent, a substantially unaltered fluorescence pattern of items (a) to (c) is indicative for the suitability of the combination of the amyloid depleting drug and the agent in the treatment of an amyloidosis or amyloid-related disease and an substantially altered fluorescence pattern of any one of items (a) to (c) indicates an impact of the agent on the amyloid depleting activity of the amyloid depleting drug. An enhanced fluorescence signal emitted from the amyloid deposit indicates that the binding of the amyloid depleting drug is more efficient in the presence of the agent and thus, indicates a synergistic effect on the amyloid depleting activity of the amyloid depleting drug. A reduced fluorescence signal emitted from the amyloid deposit indicates that the binding of the amyloid depleting drug is less efficient in the presence of the agent and thus, indicates a detrimental effect on the amyloid depleting activity of the amyloid depleting drug. In addition, or alternatively, an enhanced intracellular fluorescence signal in the phagocyticvesicles indicates an enhanced macrophage mediated internalization of amyloid and thus,indicates a synergistic effect on the amyloid depleting activity of the amyloid depleting drug.A reduced intracellular fluorescence signal in the phagocytic vesicles indicates a reducedmacrophage mediated internalization of amyloid and thus, indicates a detrimental effect on theamyloid depleting activity of the amyloid depleting drug.In addition, or alternatively, an enhanced separation of the punctuate fluorescence signal fromthe fluorescence signal of the amyloid indicates an enhanced macrophage mediated amyloidfragmentation and thus, indicates a synergistic effect on the amyloid depleting activity of theamyloid depleting drug. A reduced separation of the punctuate fluorescence signal from thefluorescence signal of the amyloid indicates a reduced macrophage mediated amyloidfragmentation and thus, indicates a detrimental effect on the amyloid depleting activity of theamyloid depleting drug.In a preferred embodiment of the methods of the present invention, the amyloid depleting drugis an anti-amyloid antibody and most preferably an anti-TTR antibody and thus, the amyloid deposit is preferably a TTR amyloid deposit, and the amyloidosis and the amyloid-related disease are preferably TTR amyloidosis or an TTR amyloid-related disease, most preferably cardiac TTR amyloidosis. Thus, the tissue section is preferably a cardiac tissue section. In thiscontext, the agent is preferably a second drug, which is preferably a drug useful in the treatmentof TTR amyloidosis, for example a TTR tetramer stabilizer, such as tafamidis, or diflunisal, or a TTR gene silencer.The amyloid depleting drug to be validated with the method of to the present invention, to becharacterized with the method of the present invention, to be subjected to quality control usingthe method of the present invention, or to be analyzed regarding the impact of an agent, forexample a second drug on its amyloid depleting activity is preferably the anti-TTR antibody ofthe present invention, most preferably antibody ALXN2220 as characterized hereinbefore. Said antibody can also be used as positive control in the methods of the present invention, in particular in the methods of screening and identifying. Accordingly, the methods of the present invention comprise the use of a positive control, which is preferably the antibody of the present invention as defined hereinbefore, and most preferably antibody ALXN2220.The high-resolution live-cell imaging uses in a preferred embodiment refractive index imagingfor cell visualization and fluorescence microscopy for amyloid imaging. If the amyloid in the tissue sections is stained with an amyloid specific fluorescent dye and the antibody is also labelled with a fluorescent dye, preferably two different dyes are used, preferably dyes with adifferent colour, e.g., a red and a green fluorescent dye.The tissue section comprising the amyloid is preferably derived from a subject suffering from an amyloidosis or an amyloid-related disease, preferably from TTR amyloidosis, most preferably from cardiac TTR amyloidosis. The present invention further relates to a kit useful for performing the method of the present invention which comprises at least a first fluorescent dye for amyloid staining and / or a second fluorescent dye for labelling of the amyloid depleting drug, and optionally instructions for use or consumables useful for performing the method, e.g. microdishes. Preferably, the kit may also comprise a negative and / or positive control, wherein the positive control can be for example the antibody as defined hereinbefore, preferably antibody ALXN2220. In the past, further assays have been developed either to determine the elimination or reductionof amyloid fibrils in a patient-derived amyloid xenograft (PDAX) non-human animal model,which comprises an implant of amyloid fibrils, upon administration of an amyloid depletingdrug, in particular an anti-TTR antibody to the animal (see WO 2020 / 094883 A1), or todetermine the potency of a target antigen binding molecule, in particular an anti-TTR antibody to mediate phagocytosis of amyloidogenic TTR (see WO 2023 / 099788 A1). These assays may be combined with the method of the present invention to enhance the accuracy of the result. For example, the method of the present invention may be performed together with a corresponding method using a patient-derived amyloid xenograft (PDAX) non-human animal model, wherein the animal is characterized by an implant of amyloid fibrils derived from the tissue or organ of a patient suffering from an amyloidosis or amyloid-related disease, wherein the amyloid and amyloid fibrils, respectively, comprise amyloid transthyretin (ATTR), and wherein the amyloid fibrils are subcutaneously or subcapsularly implanted or implanted in the kidney, the peritoneum, the muscles, the brain, the ventricles, the nerves, the eyes, the tongue, or the heart,wherein the corresponding method comprises administering the amyloid depleting drug or atest substance to the PDAX non-human animal model and determining amyloid fibrils in themodel, wherein the accelerated elimination or reduction of the amyloid fibrils uponadministration of the drug or the test substance compared to a control is indicative for the suitability of the amyloid depleting drug for the treatment of an amyloidosis or amyloid-related disease and for the amyloid depleting activity of the test substance, respectively. Definitions For the avoidance of any doubt, it is emphasized that the expressions "in some embodiments", "in a certain embodiments", "in certain instances", "in some instances", "in a further embodiment", "in one embodiment", "in a further aspect", "in a first aspect", "in a second aspect", etc., and the like are used and meant such that any of the embodiments described therein are to be read with a mind to combine each of the features of those embodiments and that the disclosure has to be treated in the same way as if the combination of the features of those embodiments and aspects would be spelled out in one embodiment. The same is true for any combination of embodiments and features of the appended claims and illustrated in the Examples, which are also intended to be combined with features from corresponding embodiments disclosed in the description, wherein only for the sake of consistency and conciseness the embodiments are characterized by dependencies while in fact each embodiment and combination of features, which could be construed due to the (multiple) dependencies must be seen to be literally disclosed and not considered as a selection among different choices. In this context, the person skilled in the art will appreciate that the embodiments and features disclosed in the Examples are intended to be generalized to any anti-TTR antibody and equivalents having substantially the same properties. As used herein, the term "about," as used herein, refers to a value that is ± 10% of a recited value, preferably within ± 5%. For example, "about 8%" can mean any percentage between 7.2% and 8.8%, preferably any percentage between 7.6% and 8.4%. In another example, "about 2 mL" can mean any volume between 1.8 mL and 1.2 mL (e.g., 1.8 mL, 1.9 mL, 1.95 mL, 2 mL, 2.05 mL, 2.10 mL, 2.15 mL, and 2.2 mL). In the context of the antibody amount as referred to herein, e.g., 50 mg / mL or 100 mg / mL, the term "about" refers to concentrations ranging from 45 mg / mL to 50 mg / mL, and preferably from 48 mg / mL to 52 mg / mL and to concentrations ranging from 90 mg / mL to 113 mg / mL, preferably from 96 mg / mL to 113 mg / mL. Accordingly, even if the term "about" is not explicitly used, the above indicated concentration ranges apply, e.g., when reference is made to 50 mg / mL, concentrations ranging from 45 mg / mL to 55 mg / mL are included and when reference is made to 100 mg / mL, concentrations ranging from 90 mg / mL to 113 mg / mL are included since these ranges are within the experimental deviation. In connection with the present disclosure, the term "and / or" is understood to mean that allmembers of a group which are connected by the term "and / or" are disclosed cumulatively inany combination, both alternatively to each other and in each case to each other. This means for the expression "A, B and / or C" that the following disclosure content is to be understoodthereunder: a) A or B or C; or b) (A and B); or c) (A and C); or d) (B and C); or e) (A and Band C).An "antibody" as used herein refers to a population of immunoglobulin molecules thatspecifically bind to a target antigen. The term "antibody" is understood to encompass not onlya singular molecular entity but also variants of the antibody that may arise from post- translational modifications, such as glycosylation, deamidation, lysine clipping, and pyroglutamate formation. These modifications may result in a heterogeneous population where individual molecules within the batch differ in the number or type of modifications present.Therefore, the term "antibody" refers to this population as a whole, including such modifiedand unmodified forms. The phrases "essentially free of NaCl" and "substantially free of NaCl" in the context of theformulation / pharmaceutical composition of the present disclosure mean that the pharmaceuticalcomposition / formulation contains either no NaCl or only trace amounts that are considered negligible for the intended use of the product and, i.e., that NaCl is present at such a low level that it does not affect the formulation’s performance, stability, safety, or efficacy. Furthermore, the phrases may also refer to formulations / pharmaceutical compositions to which NaCl is not intentionally added, but which may comprise either Na2+or Cl- due to the presence of salts of other excipients, for example histidine-HCl. The phrases "essentially free of" and "substantially free of" in the context of theformulation / pharmaceutical composition of the present disclosure mean that the pharmaceuticalcomposition / formulation does not contain the substance which is referred to or only trace amounts that are considered negligible for the intended use of the product and, i.e., that the substance is present at such a low level that it does not affect the formulation’s performance, stability, safety, or efficacy.As used herein, the term "binding potency" refers to a characteristic corresponding to aquantitative measure of biological activity (e.g., TTR-binding). A binding potency assay (e.g., an ELISA assay) can be used to measure the ability of an anti-TTR antibody or antigen-binding fragment thereof of the disclosure to elicit a specific response in a disease-relevant system (e.g., a subject having ATTR-CM, such as WT-ATTR-CM). The activity measured in the assay is a surrogate for an intended biological effect and can be used to assess the maintenance of that effect over time (e.g., following storage). As used herein, the expressions "is capable of binding" and "binds to" refers to the capability of the antibody or antigen-binding fragment thereof to bind to, for example aggregated TTR, under experimental conditions (for example in an ELISA assay). As used herein, the term "pharmaceutical composition" refers to a mixture containing a therapeutic agent (e.g., an anti-TTR antibody described herein), optionally in combination withone or more pharmaceutically acceptable excipients, diluents, and / or carriers. Thepharmaceutical composition is, for example, formulated for administration to a subject, such as a mammal, e.g., a human, in order to prevent, treat or control a particular disease or condition affecting, or that may affect, the subject (e.g., ATTR-CM, such as WT-ATTR-CM).As used herein, the term "pharmaceutically acceptable" refers to those compounds, materials,compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues a subject, such as a mammal (e.g., a human) withoutexcessive toxicity, irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit / risk ratio. The term "between" as used herein includes the endpoints.As used herein, room temperature (RT) is defined as between 15 to 25 °C according to theEuropean Pharmacopoeia."Percent (%) sequence identity" with respect to a reference polynucleotide or polypeptidesequence is defined as the percentage of nucleic acids or amino acids in a candidate sequence that are identical to the nucleic acids or amino acids in the reference polynucleotide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid or amino acid sequence identity can be achieved in various ways that are within the capabilities of one of skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, or Megalign software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For example, percent sequence identity values may be generated using the sequence comparison computer program BLAST. As an illustration, the percent sequence identity of a given nucleic acid or amino acid sequence, A, to, with, or against a given nucleic acid or amino acid sequence, B, (which can alternatively be phrased as a given nucleic acid or amino acid sequence, A that has a certain percent sequence identity to, with, or against a given nucleic acid or amino acid sequence, B) is calculated as follows: 100 multiplied by (the fraction X / Y) where X is the number of nucleotides or amino acids scored as identical matches by a sequence alignment program (e.g., BLAST) in that program’s alignment of A and B, and where Y is the total number of nucleic acids in B. It will be appreciated that where the length of nucleic acid or amino acid sequence A is not equal to the length of nucleic acid or amino acid sequence B, the percent sequence identity of A to B will not equal the percent sequence identity of B to A.As used herein, the terms "treat" or "treatment" refer to both therapeutic treatment andprophylactic or preventative measures, in which the object is to prevent or slow down (lessen) an undesired physiological change or disorder, such as the development of cardiac deficiency. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission(whether partial or total), whether detectable or undetectable. "Treatment" can also meanprolonging survival (e.g., prolonging survival of a human subject having ATTR for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more years, e.g., for the lifetime of the subject) as compared to expected survival if not receiving treatment. Those in need of treatment include those already with the condition or disorder as well as those prone to have the condition or disorder or those in which the manifestation of the condition or disorder is to be prevented. "pH dead band" means a small range around the setpoint within which pH fluctuations aretolerated before correction occurs. A "pH dead band of 0.05" means that the pH is allowed tofluctuate by ±0.05 units around the target pH before corrective action, like adjusting with acidor base, is applied. The term "isolated" in the context of a polypeptide or an antibody, refers to a molecule that hasbeen removed from its native environment, e.g., cell culture. An “isolated” antibody issubstantially free of material from the cellular source from which it is derived. In some embodiments, isolated molecules, e.g., polypeptides, soluble proteins, antibodies, polynucleotides, vectors, cells, are those that have been purified to a degree that they are nolonger in a form in which they are found in nature. In some embodiments, the isolated moleculeis substantially pure. The term “substantially purified” as used herein refers to material that isat least 50% pure (e.g., free from contaminants), at least 90% pure, at least 95% pure, at least98% pure, or at least 99% pure. In some embodiments, the purified molecule is ofpharmaceutical grade. The term "polynucleotide" is intended to encompass a singular nucleic acid as well as plural nucleic acids, and refers to an isolated nucleic acid molecule or construct, e.g., messenger RNA (mRNA) or plasmid DNA (pDNA). A polynucleotide may comprise a conventional phosphodiester bond or a non-conventional bond (e.g., an amide bond, such as found in peptide nucleic acids (PNA)). The term "nucleic acid" refers to any one or more nucleic acid segments, e.g., DNA or RNA fragments, present in a polynucleotide. By "isolated" nucleic acid or polynucleotide is intended a nucleic acid molecule, DNA or RNA, which has been removed from its native environment. For example, a recombinant polynucleotide encoding an antibody contained in a vector is considered isolated for the purposes of the present disclosure. Further examples of an isolated polynucleotide include recombinant polynucleotides maintained in heterologous host cells or purified (partially or substantially) polynucleotides in solution.Isolated RNA molecules include in vivo or in vitro RNA transcripts of polynucleotides of thepresent disclosure. Isolated polynucleotides or nucleic acids according to the present disclosure further include such molecules produced synthetically. In addition, polynucleotide or a nucleic acid may be or may include a regulatory element such as a promoter, ribosome binding site, or a transcription terminator. Brief Description of the DrawingsFig. 1: cIEF Acidic % of ALXN2220 GMP Drug Substance Batches.Fig. 2: Amount of mannose-containing glycans (Man5) of ALXN2220 GMP Drug SubstanceBatches.Fig. 3: iCIEF Acidic % of Small-Scale Study.Fig. 4: Man 5 profile of Small-Scale Study.Fig. 5: Online pH of Small-Scale Bioreactors.Fig. 6: Glycosylation profile of ALXN2220 as determined by LCMS.Fig. 7: ATTR deposits in myocardium tissue sections were identified using Amytracker 680,a red fluorescent dye specific for amyloid. ALXN2220 labelled with the green fluorescent dye A488 selectively binds to ATTR as indicated by the overlap betweenred and green fluorescence. (A) Refractive index imaging of a myocardium tissuesection; (B) Identification of ATTR deposits in myocardium tissue section with the redfluorescent dye Amytracker 680; (C) Visualizing of ALXN2220 labelled with thegreen fluorescent dye A488; (D) Overlap between the red and green fluorescence indicates that ALXN2220 binds to ATTR.Fig. 8: ALXN2220 triggered amyloid phagocytosis by macrophages. The punctate andintracellular red fluorescence pattern revealed the presence of ATTR amyloid in phagocytic vesicles. Macrophages presented a broad range of phagocytic activity indicated by the number of red fluorescent vesicles. Fig. (A), (B), (C), and (D) each represent an exemplarily fluorescence image, wherein the right image is an enlarged section of the left image.Fig. 9: Multinucleated macrophage successively detaches fragments of amyloid from a largedeposit. The fluorescence images shown the process of fragment detachment over time(after 2.5 h, 3 h, 4 h, 12 h, 13 h, and 13.5 h).Fig. 10: The macrophage was observed separating a thin and elongated ATTR deposit fromthe adjacent cardiomyocytes, moving the deposit by more than 20 µm. Themacrophage also severed a protruding large amyloid deposit, detaching small andlarge fragments of amyloid. The fluorescence images show the movement of thedeposits over time (after 1 h, 4 h, 5.5 h, 6 h.11 h, 13.5 h, and 16 h). Detailed DescriptionProvided herein is, inter alia, an anti-transthyretin (TTR) antibody, correspondingpolynucleotides and expression vectors as well as compositions (e.g., pharmaceuticalcompositions) and related articles of manufacture that contain the anti-TTR antibody as a drug.Additionally, provided herein are, inter alia, methods of treating or preventing transthyretin- mediated amyloidosis (ATTR) in a subject in need thereof using the pharmaceuticalcompositions. Furthermore, methods for validating, identifying, and screening of an amyloiddepleting drug using high-resolution live-cell imaging as well as methods for producing a pharmaceutical composition of an amyloid depleting drug and methods for quality control are provided herein including kits suitable for use in said methods. Antibodies and antibody composition of the present disclosure The present disclosure relates to a monoclonal human-derived anti-TTR antibody, which comprises an immunoglobulin light chain (LC) and an immunoglobulin heavy chain (HC) with the amino acid sequences set forth in Table 1, below. The antibody may have a HC having the amino acid sequence of SEQ ID NO: 7 and a LC having the amino acid sequence of SEQ ID NO: 8, wherein X1 is absent, glutamine, or a pyroglutamate (pE); X2is methionine or oxidized methionine; X3is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine or deamidated asparagine; X5 is proline or amidated proline; X6 is absent or glycine; and X7is absent or lysine, and a LC having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the glutamine (X1), the glycine (X6) and lysine (X7) are present, and wherein the amino acids at positions X2, X3, X4 and X5 are either modified as indicated in Table 1 (e.g., oxidized, deamidated, succinimide comprising, and / or amidated) or unmodified. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the glutamine (X1) is absent or modified to pyroglutamate, preferably modified to pyroglutamate, and wherein glycine (X6) and lysine (X7) are present, and wherein the amino acids at positions X2, X3, X4 and X5 are either modified as indicated above or unmodified. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the lysine (X7) is absent, wherein the glycine (X6) and the glutamine (X1) are present, and wherein the amino acids at positions X2, X3, X4and X5are either modified as indicated above or unmodified. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, in which the lysine (X7) and the glycine (X6) are absent, wherein the glutamine (X1) is present, and wherein the amino acids at positions X2, X3, X4 and X5 are either modified as indicated above or unmodified. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the glutamine (X1) is absent or modified to pyroglutamate, preferably modified to pyroglutamate, wherein the lysine (X7) is absent, wherein glycine (X6) is present, and wherein the amino acids at positions X2, X3, X4and X5are either modified as indicated above or unmodified. In one embodiment, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the glutamine (X1) is absent or modified to pyroglutamate, preferably modified to pyroglutamate, wherein the lysine (X7) and the glycine (X6) are absent, and wherein the amino acids at positions X2, X3, X4and X5are either modified as indicated above or unmodified.In a preferred embodiment, the antibody of the present disclosure comprises a HC as shown inSEQ ID NO: 7, wherein the glutamine (X1) is modified to pyroglutamate, wherein the lysine (X7) is absent, and wherein the amino acids at positions X2, X3, X4 and X5 are modified as indicated above or unmodified. In a preferred embodiment, X2, X3, X4 and X5 are unmodified. Thus, preferably, the antibody of the present disclosure comprises a HC as shown in SEQ ID NO: 7, wherein the glutamine (X1) is modified to pyroglutamate, wherein the lysine (X7) is absent, and in which the amino acids at positions X2, X3, X4 and X5 are unmodified. The antibody of the present disclosure is preferably composed of two HCs, each having an amino acid sequence set forth in SEQ ID NO: 7, and two LCs, each having an amino acid sequence set forth in SEQ ID NO: 8, and wherein in each HC the glutamine (X1) at the N- terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7) is absent, and the heavy chain is N-glycosylated (e.g., at least one amino acid in the HC is N-glycosylated), preferably wherein the N-glycosylation site is at position Asn300, and wherein the amino acids at position X2, X3, X4, and X5 are either modified or unmodified, preferably unmodified.In one embodiment, the antibody has a HC having the amino acid sequence of SEQ ID NO: 39with the PTMs as detailed in the summary of the invention section, and a LC having the aminoacid sequence of SEQ ID NO: 8. In particular, the antibody may have a HC having the aminoacid sequence of SEQ ID NO: 39 and a LC having the amino acid sequence of SEQ ID NO: 8,wherein X1is absent, glutamine, or a pyroglutamate (pE), preferably a pE; X2is methionine or oxidized methionine, preferably methionine; X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide, preferably asparagine; X4is asparagine or deamidated asparagine, preferably asparagine; X5is proline or amidated proline, preferably proline; X6 is absent or glycine, preferably glycine; X7 is absent or lysine, preferably absent; XIis asparagine or deamidated asparagine, preferably asparagine; XII is methionine or oxidized methionine, preferably methionine; XIII is methionine or oxidized methionine, preferably methionine; XIVis aspartate or iso-aspartate, preferably aspartate; XV is asparagine or glycosylated asparagine, preferably glycosylated asparagine; XVI is methionine or oxidized methionine, preferably methionine; and XVIIis methionine or oxidized methionine, preferably methionine, and a LC having the amino acid sequence of SEQ ID NO: 8. The antibody may have a HC having the amino acid sequence of SEQ ID NO: 9 and a LC having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the heavy chain of the antibody of the present disclosure has lost the C-terminal lysine, i.e., the antibody has undergone C-terminal lysine clipping and the C-terminallysine is cleaved or absent, respectively. In particular, the C-terminal lysine as shown in SEQID NO: 9 is absent, preferably from each heavy chain of the antibody. Said sequence, i.e., thesequence of the heavy chain with an absent C-terminal lysine is set forth in SEQ ID NO: 10. Alternatively, the glutamine at the N-terminal is modified as pyro-glutamic acid, i.e., the heavy chain of the antibody as shown in SEQ ID NO: 9 has undergone N-terminal glutaminylcyclization. Said sequence, i.e., the sequence of the heavy chain without N-terminal glutamineis set forth in SEQ ID NO: 11. Instead the N-terminus is cyclized and comprises pyroglutamate, respectively. In a preferred embodiment, the heavy chain of the anti-TTR antibody of the present disclosure has lost the C-terminal lysine as shown in SEQ ID NO: 9, i.e., the C-terminal lysine is cleaved or absent, respectively and the glutamine at the N-terminal as shown in SEQ ID NO: 9 ismodified as pyroglutamate. Said sequence, i.e., the sequence of the heavy chain without C-terminal lysine and without N-terminal glutamine is set forth in SEQ ID NO: 12. Instead the N- terminus is cyclized and comprises pyroglutamate, respectively. In addition, or alternatively, the antibody is glycosylated, in particular N-glycosylated. More particularly, the heavy chain of the antibody is glycosylated and even more particularly at N300of the heavy chain (SEQ ID NO: 9).Thus, the present disclosure provides different species of the antibodies, i.e., antibodies beingencoded by the same gene and comprise the same primary amino acid sequence, but which have been posttranslational modified to a different extent. As mentioned above, the most prominent PTMs are the modification of the C-terminus by clipping off the lysine and the pyroglutamate formation at the N-terminus as well as N-glycosylation.Furthermore, the theoretical molecular weight of the antibody of the present disclosure is 144.2kDa, and the weight determined by mass spectrometry (MS) is 144.2 kDa (deglycosylated) and between 147.0 and 147.6 kDa (intact IgG1), respectively. Thus, in one embodiment, theantibody comprised in the pharmaceutical composition of the present disclosure has a molecularweight of about 150 kDa, preferably of about 147 kDa.In one embodiment, the antibody of the present disclosure comprises at least 8 disulfide bridges,preferably at the following positions: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in SEQ IDNOs: 7 and 8, with SEQ ID NO: 7 having the N-terminal glutamine (X1) and to SEQ ID NOs:9 and 8, respectively, with SEQ ID NO: 9 having the N-terminal glutamine (Q).In one embodiment, the HC of the antibody of the present disclosure my further comprises asignal peptide having an amino acid sequence of SEQ ID NO: 17, wherein the sequence including the HC and the signal peptide is set forth in SEQ ID NO: 19. In addition, oralternatively, the LC of the antibody of the present disclosure further comprises a signal peptide having an amino acid sequence of SEQ ID NO: 18, wherein the sequence including the HC and the signal peptide is set forth in SEQ ID NO: 20.The present disclosure further relates to compositions comprising either one species of theabove-described antibodies, preferably antibodies comprising a LC as shown in SEQ ID NO: 8 and a HC as shown in SEQ ID NO: 7, in which the glutamine (X1) is modified to pyroglutamate and in which the lysine (X7) is absent, and in which the amino acids at positions X2, X3, X4andX5 are unmodified, and in which X6 is present, or antibodies comprising a LC as shown in SEQID NO: 8 and a HC as shown in SEQ ID NO: 9 from which the C-terminal lysine (K) is clippedoff and in which the N-terminal glutamine is modified to pyroglutamate, or antibodiescomprising a HC as shown in SEQ ID NO: 39 in which the glutamine (X1) is modified topyroglutamate and in which the lysine (X7) is absent, and in which the amino acids at positionsX2, X3, X4 and X5 are unmodified, in which the amino acid at X6 is present, and preferably inwhich the asparagine (XV) is glycosylated, and in which the amino acids at positions XI, XII, XIII, XIV, XVI, XVI are unmodified. More preferred, the composition comprises a mixture of the above-described antibody species,wherein preferably in about 90% to 100%, (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98%, 99%, or 100%, preferably about 100% (99.9%)) of the antibodies present in thecomposition, the N-terminal is modified as pyro-glutamic acid and in about 90% to 100% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, preferably about 96% (95.8%)) of the antibodies present in the composition, the C-terminal lysine is clipped of. Table 1. Anti-TTR Antibody Sequences SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: VH-CDR1 1 / 38 SRSSYSRSSYWG (according to Kabat et al., U.S. Dept. of Health and Human Services, "Sequences of Proteins of Immunological Interest" (1983)) VH-CDR2 2 GIYHSGNTYDNPSLKSVH-CDR3 3 IVPGGDAFDIVL-CDR1 4 RASQSVGTYLNVL-CDR2 5 AASSLQS SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO:VL-CDR3 6 QQSYSSPPTHC 7 X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSGNTYDNPSLKSRLTMSVDTSKNQFSLNLRSV TAADTAVYYCARIVPGGDAFDIWGQGTMVTVSSASTKGPSVFP LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLX2ISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESX4G QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSX5X6X7the amino acid residues of the constant region are underlined X1 is absent, glutamine, or a pyroglutamate (pE); X2 is methionine or oxidized methionine; X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine or deamidated asparagine; X5 is proline or amidated proline; X6 is absent or glycine; and X7 is absent or lysine; and HC 39 X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSGXITYDNPSLKSRLTXIISVDTSKNQFSLNLRSV TAADTAVYYCARIVPGGDAFDIWGQGTXIIIVTVSSASTKGPSVF PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK RVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLX2ISRTPE VTCVVVDVSHEDPEVKFNWYVXIVGVEVHNAKTKPREEQYXVS TYRVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEXVITKNQVSLTCLVKGFYPSDIAVEWES X4GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVXVIIHEALHNHYTQKSLSLSX5X6X7 the amino acid residues of the constant region are underlined X1is absent, glutamine, or a pyroglutamate (pE); X2is methionine or oxidized methionine; X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X5is proline or amidated proline; X6 is absent or glycine; X7 is absent or lysine; XI is asparagine or deamidated asparagine;XIIis methionine or oxidized methionine; XIIIis methionine or oxidized methionine; SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: XIVis aspartate or iso-aspartate; XVis asparagine or glycosylated asparagine; XVI is methionine or oxidized methionine; and XVII is methionine or oxidized methionine LC 8 DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSSPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC HC 9 Q*LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSGNTYDNPSLKSRLTMSVDTSKNQFSLNLRSV TAADTAVYYCARIVPGGDAFDIWGQGTMVTVSSASTKGPSVFP LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGK* the amino acid residues of the constant region are underlined *the C-terminal lysine (K) is optional and / or the N-terminal glutamine(Q) undergoes intramolecular cyclization, resulting in the formation of pyroglutamateHC – without 10 QLQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKC-terminal GLEWIGGIYHSGNTYDNPSLKSRLTMSVDTSKNQFSLNLRSVT AADTAVYYCARIVPGGDAFDIWGQGTMVTVSSASTKGPSVFPL lysine APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGHC – without 11 LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGN-terminal LEWIGGIYHSGNTYDNPSLKSRLTMSVDTSKNQFSLNLRSVTA ADTAVYYCARIVPGGDAFDIWGQGTMVTVSSASTKGPSVFPLA glutamine** PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVE PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGKHC – without 12 LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGC-terminal LEWIGGIYHSGNTYDNPSLKSRLTMSVDTSKNQFSLNLRSVTA ADTAVYYCARIVPGGDAFDIWGQGTMVTVSSASTKGPSVFPLA lysine and N- PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA terminal VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVE PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC glutamine** VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGHC -original 13 cagctgcagctgcaggagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcagtgtctctggtggctccatcatcagtaggagttcctactggggctggatccgccagcccccaggg aaggggctggagtggattgggggtatctatcatagtgggaacacttacgacaacccgtccctcaaga gtcgactcaccatgtccgtagacacgtcgaagaaccagttctccctgaatctgaggtctgtgaccgcc gcagacacggctgtgtattactgtgcgaggatagtgccggggggtgatgcttttgatatctggggcc aagggacaatggtcaccgtctcttcggcgtcgaccaagggcccatcggtcttcccgctagcaccctc ctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaac ctgtgacggtctcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctac agtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccaga cctacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaat cttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtctt cctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtcacatgcgtggtg gtggacgtgagccacgaagaccctgaggtcaagttcaactggtacgtggacggcgtggaggtgca taatgccaagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctca ccgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcc cagcccccatcgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacac cctgcccccatcccgggaggagatgaccaagaaccaggtcagcctgacctgcctggtcaaaggct tctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaagac cacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtggacaagagc aggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacg cagaagagcctctccctgtccccgggtaaaLC - original 14 gacatccagatgacccagtctccatcctccctgtctgcatctgtaggagacagagtcacaatcgcttgccgggccagtcagagcgttggcacctatttaaattggtatcagcagaaaagagggaaagcccctaa actcctcatctttgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgg gacagatttcactctcaccatcagcagtctgcaacctgaagactttgcaacttactactgtcaacagag ttacagttctcctccaacgttcggccaagggaccaaggtggagatcaaacgtacggtggctgcacca tctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgcctgctgaa taacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggtaactcc caggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgc tgagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagc tcgcccgtcacaaagagcttcaacaggggagagtgt SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: HC - codon 15 cagctgcagctgcaggagtccggacctggcctggtgaagccctccgagaccctgagcctgacctgoptimized ttccgtgagcggcggctccatcatctccaggtcctcctactggggctggattaggcagccccctggc aagggcctggaatggatcggcggcatctaccactccggcaacacctacgacaacccctccctgaa gtccaggctgaccatgtccgtggacacctccaagaaccagttctccctgaacctgaggtccgtcaca gccgccgataccgccgtgtactactgtgctaggatcgtgcctggcggcgacgcctttgacatctggg gccagggcaccatggtgaccgtgtcctccgctagcaccaagggcccatcggtcttccccctggcac cctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccg aaccggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggccgtc ctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcaccc agacctacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaagcgggttgagccc aaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtca gtcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtcacatgcgt ggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtacgtggacggcgtggagg tgcataatgccaagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtc ctcaccgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaagcc ctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgta caccctgcccccatcccgggaggagatgaccaagaaccaggtcagcctgacctgcctggtcaaag gcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaag accacgcctcccgtgctggactccgacggctccttcttcctctacagcaagctcaccgtggacaaga gcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccactaca cgcagaagagcctctccctgtctccgggtaaatga LC - codon 16 gacatccagatgacccagtcccctagctccctgtccgcttccgtgggcgatcgggtgaccattgcctoptimized gcagggcttcccagtccgtgggcacctacctgaactggtaccagcagaagaggggcaaggcccc caagctgctgatcttcgccgcttcctccctgcagtccggcgtgccttccaggttttccggctccggctc cggcaccgatttcaccctgaccatctcctccctgcaacccgaggacttcgccacctactactgccag cagtcctactcctccccccctacattcggccagggcaccaaggtggagatcaagcgtacggtggct gcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgcct gctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggt aactcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccc tgacgctgagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggc ctgagctcgcccgtcacaaagagcttcaacaggggagagtgttga HC signal17 MKHLWFFLLLVAAPRWVLSpeptide LC signal18 MDMRVPAQLLGLLLLWLRGARCpeptide HC including19 MKHLWFFLLLVAAPRWVLSQLQLQESGPGLVKPSETLSLTCSVHC signal SGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSGNTYDNPSLKSR LTMSVDTSKNQFSLNLRSVTAADTAVYYCARIVPGGDAFDIWG peptide QGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK LC including20 MDMRVPAQLLGLLLLWLRGARCDIQMTQSPSSLSASVGDRVTILC signal ACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRT peptide VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC HC signal21 atgaagcacctgtggttcttcctcctgctggtggcggctcccagatgggtcctgtccpeptide LC signal22 atggacatgagggtccccgctcagctcctggggctcctgctactctggctccgaggtgccagatgtpeptide HC codon23 atgaagcacctgtggttcttcctcctgctggtggcggctcccagatgggtcctgtcccagctgcagctoptimized gcaggagtccggacctggcctggtgaagccctccgagaccctgagcctgacctgttccgtgagcg gcggctccatcatctccaggtcctcctactggggctggattaggcagccccctggcaagggcctgg including HC aatggatcggcggcatctaccactccggcaacacctacgacaacccctccctgaagtccaggctga signal peptide ccatgtccgtggacacctccaagaaccagttctccctgaacctgaggtccgtcacagccgccgatac cgccgtgtactactgtgctaggatcgtgcctggcggcgacgcctttgacatctggggccagggcac catggtgaccgtgtcctccgctagcaccaagggcccatcggtcttccccctggcaccctcctccaag agcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgac ggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggccgtcctacagtcctc aggactctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacat ctgcaacgtgaatcacaagcccagcaacaccaaggtggacaagcgggttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttc cccccaaaacccaaggacaccctcatgatctcccggacccctgaggtcacatgcgtggtggtggac gtgagccacgaagaccctgaggtcaagttcaactggtacgtggacggcgtggaggtgcataatgcc aagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcct gcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcccagccc ccatcgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgccc ccatcccgggaggagatgaccaagaaccaggtcagcctgacctgcctggtcaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaagaccacgcctc ccgtgctggactccgacggctccttcttcctctacagcaagctcaccgtggacaagagcaggtggca gcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgcagaagag cctctccctgtctccgggtaaatga LC codon24 atggacatgagggtccccgctcagctcctggggctcctgctactctggctccgaggtgccagatgtgoptimized acatccagatgacccagtcccctagctccctgtccgcttccgtgggcgatcgggtgaccattgcctg cagggcttcccagtccgtgggcacctacctgaactggtaccagcagaagaggggcaaggccccc including LC aagctgctgatcttcgccgcttcctccctgcagtccggcgtgccttccaggttttccggctccggctcc signal peptide ggcaccgatttcaccctgaccatctcctccctgcaacccgaggacttcgccacctactactgccagc agtcctactcctccccccctacattcggccagggcaccaaggtggagatcaagcgtacggtggctg SEQ Domain / ID Amino Acid Sequence / Nucleotide Sequence Region NO: caccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgcctg ctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccct gacgctgagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcc tgagctcgcccgtcacaaagagcttcaacaggggagagtgttga CDR = complimentary determining region; VH = heavy chain variable region; VL = light chain variable region; HC = heavy chain; LC = light chain** the N-terminal glutamine is absent and / or has been modified to pyroglutamate, which isalso referred to as N-terminal cyclization, preferably, the N-terminal glutamine has beenmodified to pyroglutamate In certain embodiments, the CDRs may contain one or more amino acid residues, particularly in CDRs that contain multiple tryptophan (W) residues. These small differences in CDR length may be attributed to different application of Martin's rules, according to which, VHCDR1 ends just before a tryptophan (W), typically preceding the motif W-valine (WV), W-isoleucine (WI), or W-alanine (WA). Since the heavy chain CDR1 of NI006 / ALXN2220 contains the sequence 31-SRSSYWGWI-39 (SEQ ID NO: 37), the boundary for this CDR may end in Y or G, both of which precede W, depending on how the rule is applied. For avoidance of doubt, the broadest definition of VHCDR1 comprising SRSSY is used herein. In embodiments, the VHCDR1 comprises SRSSYWG (SEQ ID NO: 38). Polynucleotides and nucleic acid molecules of the present disclosureA polynucleotide encoding an antibody of the present disclosure can be composed of anypolyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. For example, a polynucleotide encoding an antibody can be composedof single- and double-stranded DNA, DNA that is a mixture of single- and double-strandedregions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-stranded and double-stranded regions. In addition, a polynucleotide encoding an antibody can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide encoding an antibody may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus,"polynucleotide" embraces chemically, enzymatically, or metabolically modified forms. Anisolated polynucleotide encoding a non-natural variant of a polypeptide derived from an immunoglobulin (e.g., an immunoglobulin heavy chain portion or light chain portion) can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of the immunoglobulin such that one or more amino acid substitutions,additions or deletions are introduced into the encoded protein. Mutations may be introduced bystandard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more non-essential amino acid residues. As is well known, RNA may be isolated from the original B cells, hybridoma cells or from other transformed cells by standard techniques, such as a guanidinium isothiocyanate extraction and precipitation followed by centrifugation or chromatography. Where desirable, mRNA may be isolated from total RNA by standard techniques such as chromatography on oligo dT cellulose. Suitable techniques are familiar in the art. In one embodiment, cDNAs that encode the light and the heavy chains of the antibody may be made, either simultaneously or separately, using reverse transcriptase and DNA polymerase in accordance with well-known methods. PCR may be initiated by consensus constant region primers or by more specific primers based on the published heavy and light chain DNA and amino acid sequences. As discussed above, PCR also may be used to isolate DNA clones encoding the antibody light and heavy chains. In this case the libraries may be screened by consensus primers or larger homologous probes, such as human constant region probes. DNA, typically plasmid DNA, may be isolated from the cells using techniques known in the art, restriction mapped and sequenced in accordance with standard, well known techniques set forth in detail, e.g., in the foregoing references relating to recombinant DNA techniques. Ofcourse, the DNA may be synthetic according to the present disclosure at any point during theisolation process or subsequent analysis.In this context, the present disclosure also relates to a polynucleotide encoding the antibody ofthe present disclosure. In particular, the present disclosure relates to a polynucleotide encodingat least one of the immunoglobulin chains of the antibody of the present disclosure. In a preferred embodiment of the present disclosure, the polynucleotide comprises, consists essentially of, or consists of a nucleic acid having a polynucleotide sequence of the HC or LC as depicted in Table 1. The polynucleotides may be produced or manufactured by any method known in the art. For example, if the nucleotide sequence of the antibody is known, a polynucleotide encoding the antibody may be assembled from chemically synthesized oligonucleotides, e.g., as described in Kutmeier et al., BioTechniques 17 (1994), 242, which, briefly, involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligating of those oligonucleotides, and then amplification of the ligated oligonucleotides by PCR. Alternatively, a polynucleotide encoding an antibody, or antigen-binding fragment, variant, or derivative thereof may be generated from nucleic acid from a suitable source. If a clone containing a nucleic acid encoding a particular antibody is not available, but the sequence of the antibody molecule is known, a nucleic acid encoding the antibody may be chemically synthesized or obtained from a suitable source (e.g., an antibody cDNA library, or a cDNA library generated from, or nucleic acid, preferably polyA+RNA, isolated from, any tissue or cells expressing the TTR-specific antibody, such as hybridoma cells selected to express an antibody) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence or by cloning using an oligonucleotide probe specific for the particular gene sequence to identify, e.g., a cDNA clone from a cDNA library that encodes the antibody. Amplified nucleic acids generated by PCR may then be cloned into replicable cloning vectorsusing any method well known in the art. Accordingly, in one embodiment of the presentdisclosure the cDNA encoding an antibody, immunoglobulin chain, or fragment thereof is usedfor the production of an anti-TTR antibody.In certain embodiments, the polynucleotide or nucleic acid is DNA. In the case of DNA, a polynucleotide comprising a nucleic acid which encodes a polypeptide normally may include a promoter and / or other transcription or translation control elements operable associated with one or more coding regions. An operable association is when a coding region for a gene product, e.g., a polypeptide, is associated with one or more regulatory sequences in such a way as to place expression of the gene product under the influence or control of the regulatory sequence(s). Two DNA fragments (such as a polypeptide coding region and a promoter associated therewith) are "operable associated" or "operable linked" if induction of promoter function results in the transcription of mRNA encoding the desired gene product and if the nature of the linkage between the two DNA fragments does not interfere with the ability of the expression regulatory sequences to direct the expression of the gene product or interfere with the ability of the DNA template to be transcribed. Thus, a promoter region would be operable associated with a nucleic acid encoding a polypeptide if the promoter was capable of effecting transcription of that nucleic acid. The promoter may be a cell-specific promoter that directs substantial transcription of the DNA only in predetermined cells. Other transcription control elements, besides a promoter, for example enhancers, operators, repressors, and transcription termination signals, can be operable associated with the polynucleotide to direct cell-specific transcription. Suitable promoters and other transcription control regions are disclosed herein. A variety of transcription control regions are known to those skilled in the art. These include, without limitation, transcription control regions which function in vertebrate cells, such as, but not limited to, promoter and enhancer segments from cytomegaloviruses (the immediate early promoter, in conjunction with intron-A), simian virus 40 (the early promoter), and retroviruses (such as Rous sarcoma virus). Other transcription control regions include those derived from vertebrate genes such as actin, heat shock protein, bovine growth hormone and rabbit ß-globin, as well as other sequences capable of controlling gene expression in eukaryotic cells. Additional suitable transcription control regions include tissue-specific promoters and enhancers as well as lymphokine-inducible promoters (e.g., promoters inducible by interferons or interleukins). Similarly, a variety of translation control elements are known to those of ordinary skill in the art. These include, but are not limited to ribosome binding sites, translation initiation and termination codons, and elements derived from picornaviruses (particularly an internal ribosome entry site, or IRES, also referred to as a CITE sequence).In other embodiments, a polynucleotide of the present disclosure is RNA, for example, in theform of messenger RNA (mRNA).Polynucleotide and nucleic acid coding regions of the present disclosure may be associated withadditional coding regions which encode secretory or signal peptides, which direct the secretion of a polypeptide encoded by a polynucleotide of the present disclosure. According to the signal hypothesis, proteins secreted by mammalian cells have a signal peptide or secretory leader sequence which is cleaved from the mature protein once export of the growing protein chain across the rough endoplasmic reticulum has been initiated. Those of ordinary skill in the art areaware that polypeptides secreted by vertebrate cells generally have a signal peptide fused to theN-terminus of the polypeptide, which is cleaved from the complete or "full-length" polypeptide to produce a secreted or "mature" form of the polypeptide. In certain embodiments, the native signal peptide, e.g., an immunoglobulin heavy chain or light chain signal peptide is used, or a functional derivative of that sequence that retains the ability to direct the secretion of the polypeptide that is operable associated with it. Alternatively, a heterologous mammalian signal peptide, or a functional derivative thereof, may be used. In a preferred embodiment, the signal peptides as shown as depicted in Table 1 are used in the context of the present disclosure. Expression of Antibody PolypeptidesThe polynucleotides encoding the antibodies are typically inserted in an expression vector forintroduction into host cells that may be used to produce the desired quantity of antibody. Once a polynucleotide encoding an antibody molecule or a heavy or light chain of an antibody of thedisclosure has been obtained, the vector for the production of the antibody molecule may beproduced by recombinant DNA technology using techniques well known in the art as alsodescribed in appended Example 1. Thus, methods for preparing a protein by expressing a polynucleotide containing an antibody encoding nucleotide sequence are described herein. Methods which are well known to those skilled in the art can be used to construct expression vectors containing antibody coding sequences and appropriate transcriptional and translationalcontrol signals. These methods include, for example, in vitro recombinant DNA techniques,synthetic techniques, and in vivo genetic recombination. The disclosure, thus, providesreplicable vectors comprising a nucleotide sequence encoding an antibody molecule of the disclosure, or a heavy or light chain thereof, operable linked to a promoter. Such vectors may include the nucleotide sequence encoding the constant region of the antibody molecule and the variable domain of the antibody may be cloned into such a vector for expression of the entire heavy or light chain. The term "vector" or "expression vector" is used herein to mean vectors used in accordancewith the present disclosure as a vehicle for introducing into and expressing a desired gene in ahost cell. As known to those skilled in the art, such vectors may be selected from the group consisting of plasmids, phages, viruses, and retroviruses. In general, vectors compatible withthe instant disclosure will comprise a selection marker, appropriate restriction sites to facilitate cloning of the desired gene and the ability to enter and / or replicate in eukaryotic or prokaryotic cells. For the purposes of this disclosure, numerous expression vector systems may be employed. For example, one class of vector utilizes DNA elements which are derived from animal viruses such as bovine papilloma virus, polyoma virus, adenovirus, vaccinia virus, baculovirus, retroviruses (RSV, MMTV or MOMLV), or SV40 virus. Others involve the use of polycistronic systems with internal ribosome binding sites. Additionally, cells which have integrated the DNA into their chromosomes may be selected by introducing one or more markers which allow selection of transfected host cells. The marker may provide for prototrophy to an auxotrophic host, biocide resistance (e.g., antibiotics), or resistance to heavy metals such as copper. The selectable marker gene can either be directly linked to the DNA sequences to be expressed, or introduced into the same cell by co-transformation. Additional elements may also be needed for optimal synthesis of mRNA. These elements may include signal sequences, splice signals, as well as transcriptional promoters, enhancers, andtermination signals as also described in appended Example 1.In particularly preferred embodiments the cloned light and heavy chain genes are inserted intoan expression vector, preferably into two different expression vectors (one for the heavy chain gene and one for the light chain gene) along with the signal peptide sequences as explained above. Examples of suitable vectors include, but are not limited to plasmids pcDNA3, pHCMV / Zeo, pCR3.1, pEF1 / His, pIND / GS, pRc / HCMV2, pSV40 / Zeo2, pTRACER-HCMV, pUB6 / V5-His, pVAX1, and pZeoSV2 (available from Invitrogen, San Diego, CA), and plasmid pCI (available from Promega, Madison, WI). In general, screening large numbers oftransformed cells for those which express suitably high levels if immunoglobulin heavy andlight chains is routine experimentation which can be carried out, for example, by robotic systems. Vector systems are also taught in US patent nos. 5,736,137 and 5,658,570, each of which is incorporated by reference in its entirety herein. This system provides for high expression levels, e.g., > 30 pg / cell / day. Other exemplary vector systems are disclosed e.g., in US patent no.6,413,777. In other preferred embodiments the antibodies, or antigen-binding fragments, variants, orderivatives thereof of the disclosure may be expressed using polycistronic constructs such asthose disclosed in US patent application publication no. 2003-0157641 A1 and incorporated herein in its entirety. In these expression systems, multiple gene products of interest such as heavy and light chains of antibodies may be produced from a single polycistronic construct. These systems advantageously use an internal ribosome entry site (IRES) to provide relatively high levels of antibodies. Compatible IRES sequences are disclosed in US patent no.6,193,980 which is also incorporated herein. Those skilled in the art will appreciate that such expression systems may be used to effectively produce the full range of antibodies disclosed in the instantapplication. Therefore, in one embodiment the present disclosure provides a vector comprisingthe polynucleotide encoding at least the binding domain or variable region of an immunoglobulin chain of the antibody, optionally in combination with a polynucleotide that encodes the variable region of the other immunoglobulin chain of said binding molecule. More generally, once the vector or DNA sequence encoding a monomeric subunit of the antibody has been prepared, the expression vector may be introduced into an appropriate host cell. Introduction of the plasmid into the host cell can be accomplished by various techniques well known to those of skill in the art. These include, but are not limited to, transfection including lipotransfection using, e.g., Fugene® or lipofectamine, protoplast fusion, calcium phosphate precipitation, cell fusion with enveloped DNA, microinjection, and infection withintact virus. Typically, plasmid introduction into the host is via standard calcium phosphate co-precipitation method. The host cells harboring the expression construct are grown under conditions appropriate to the production of the light chains and heavy chains, and assayed for heavy and / or light chain protein synthesis. Exemplary assay techniques include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or fluorescence-activated cell sorter analysis (FACS), immunohistochemistry and the like. The expression vector is transferred to a host cell by conventional techniques and the transfected cells are then cultured by conventional techniques to produce an antibody for use in the methodsdescribed herein. Thus, the disclosure includes host cells comprising a polynucleotide encodingan antibody of the disclosure, or a heavy or light chain thereof, which preferably are operablelinked to a heterologous promoter. In addition or alternatively the disclosure also includes hostcells comprising a vector, as defined hereinabove, comprising a polynucleotide encoding at least the binding domain or variable region of an immunoglobulin chain of the antibody, optionally in combination with a polynucleotide that encodes the variable region of the otherimmunoglobulin chain of said binding molecule. In one embodiment for the expression ofdouble-chained antibodies, a single vector or vectors encoding both the heavy and light chains may be co-expressed in the host cell for expression of the entire immunoglobulin molecule, as detailed below. The host cell may be co-transfected with two expression vectors of the disclosure, the first vector encoding a heavy chain derived polypeptide and the second vector encoding a light chain derived polypeptide. The two vectors may contain identical selectable markers which enable equal expression of heavy and light chain polypeptides. Alternatively, a single vector may be used which encodes both heavy and light chain polypeptides. In such situations, the light chain is advantageously placed before the heavy chain to avoid an excess of toxic free heavy chain;see Proudfoot, Nature 322 (1986), 52; Kohler, Proc. Natl. Acad. Sci. USA 77 (1980), 2197. Thecoding sequences for the heavy and light chains may comprise cDNA or genomic DNA. As used herein, "host cells" refers to cells which harbor vectors constructed using recombinant DNA techniques and encoding at least one heterologous gene. In descriptions of processes for isolation of antibodies from recombinant hosts, the terms "cell" and "cell culture" are used interchangeably to denote the source of antibody unless it is clearly specified otherwise. In other words, recovery of polypeptide from the "cells" may mean either from spun down whole cells, or from the cell culture containing both the medium and the suspended cells. A variety of host-expression vector systems may be utilized to express antibody molecules for use in the methods described herein. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide codingsequences, express an antibody molecule of the disclosure in situ. These include but are notlimited to microorganisms such as bacteria (e.g., Escherichia coli, Bacillus subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing antibody coding sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing antibody coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody codingsequences; or mammalian cell systems (e.g., COS, CHO, NSO, BLK, 293, 3T3 cells) harboringrecombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter). Preferably, bacterial cells such as E. coli, and more preferably, eukaryotic cells, especially for the expression of whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule. For example, mammalian cells such as Chinese Hamster Ovary (CHO) cells, in conjunction with a vector such as the major intermediate early gene promoter element fromhuman cytomegalovirus is an effective expression system for antibodies; see, e.g., Foecking etal., Gene 45 (1986), 101; Cockett et al., Bio / Technology 8 (1990), 2. The host cell line used for protein expression is often of mammalian origin; those skilled in the art are credited with ability to preferentially determine particular host cell lines which are best suited for the desired gene product to be expressed therein. Exemplary host cell lines include, but are not limited to, CHO (Chinese Hamster Ovary), DG44 and DUXB11 (Chinese Hamster Ovary lines, DHFR minus), HELA (human cervical carcinoma), CVI (monkey kidney line), COS (a derivative of CVI with SV40 T antigen), VERY, BHK (baby hamster kidney), MDCK, WI38, R1610 (Chinese hamster fibroblast) BALBC / 3T3 (mouse fibroblast), HAK (hamster kidney line), SP2 / O (mouse myeloma), P3x63-Ag3.653 (mouse myeloma), BFA-1c1BPT (bovine endothelial cells), RAJI (human lymphocyte) and 293 (human kidney). CHO and 293 cells are particularly preferred. Host cell lines are typically available from commercial services, the American Tissue Culture Collection or from published literature. In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. In a preferred embodiment, CHO cells and most preferably the CHO cell line K1 as shown inExample 1 is used for the expression of the polynucleotides of the present disclosure to generatethe antibodies and immunoglobulin chains, respectively. For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the antibody molecule may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which stably express the antibody molecule. A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler et al., Cell 11 (1977), 223), hypoxanthine-guaninephosphoribosyltransferase (Szybalska and Szybalski, Proc. Natl. Acad. Sci. USA 48 (1992),202), and adenine phosphoribosyltransferase (Lowy et al., Cell 22 (1980), 817) genes can beemployed in tk-, hgprt- or aprt-cells, respectively. Also, anti-metabolite resistance can be usedas the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al., Natl. Acad. Sci. USA 77 (1980), 357; O'Hare et al., Proc. Natl. Acad. Sci. USA78 (1981), 1527); gpt, which confers resistance to mycophenolic acid (Mulligan and Berg, Proc.Natl. Acad. Sci. USA 78 (1981), 2072); neo, which confers resistance to the aminoglycoside G-418 Goldspiel et al., Clinical Pharmacy 12 (1993), 488-505; Wu and Wu, Biotherapy 3 (1991), 87-95; Tolstoshev, Ann. Rev. Pharmacol. Toxicol. 32 (1993), 573-596; Mulligan, Science 260 (1993), 926-932; and Morgan and Anderson, Ann. Rev. Biochem.62 (1993), 191- 217; TIB TECH 11 (1993), 155-215; and hygro, which confers resistance to hygromycin (Santerre et al., Gene 30 (1984), 147. Methods commonly known in the art of recombinantDNA technology which can be used are described in Ausubel et al. (eds.), Current Protocols inMolecular Biology, John Wiley & Sons, NY (1993); Kriegler, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990); and in Chapters 12 and 13, Dracopoli et al. (eds), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994); Colberre-Garapin et al., J. Mol. Biol.150:1 (1981), which are incorporated by reference herein in their entireties.In vitro production allows scale-up to give large amounts of the desired polypeptides.Techniques for mammalian cell cultivation under tissue culture conditions are known in the artand include homogeneous suspension culture, e.g. in an airlift reactor or in a continuous stirrerreactor, or immobilized or entrapped cell culture, e.g. in hollow fibers, microcapsules, on agarose microbeads or ceramic cartridges. If necessary and / or desired, the solutions of polypeptides can be purified by the customary chromatography methods, for example gel filtration, ion-exchange chromatography, chromatography over DEAE-cellulose or (immuno-) affinity chromatography, e.g., after preferential biosynthesis of a synthetic hinge region polypeptide or prior to or subsequent to the HIC chromatography step described herein. Genes encoding antibodies, or antigen-binding fragments, variants or derivatives thereof of thedisclosure can also be expressed in non-mammalian cells such as bacteria or insect or yeast orplant cells. Bacteria which readily take up nucleic acids include members of theenterobacteriaceae, such as strains of E. coli or Salmonella; Bacillaceae, such as B. subtilis;Pneumococcus; Streptococcus, and Haemophilus influenzae. It will further be appreciated that, when expressed in bacteria, the heterologous polypeptides typically become part of inclusion bodies. The heterologous polypeptides must be isolated, purified and then assembled into functional molecules. Where tetravalent forms of antibodies are desired, the subunits will then self-assemble into tetravalent antibodies; see, e.g., international application WO 02 / 096948. In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the antibody molecule being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of an antibody molecule, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, tothe E. coli expression vector pUR278 (Ruther et al., EMBO J. 2 (1983), 1791), in which theantibody coding sequence may be ligated individually into the vector in frame with the lacZ coding region so that a fusion protein is produced; pIN vectors (Inouye and Inouye, Nucleic Acids Res. 13 (1985), 3101-3109; Van Heeke and Schuster, J. Biol. Chem. 24 (1989), 5503- 5509); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption and binding to a matrix of glutathione- agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety. In addition to prokaryotes, eukaryotic microbes may also be used. Saccharomyces cerevisiae, or common baker's yeast, is the most commonly used among eukaryotic microorganismsalthough a number of other strains are commonly available, e.g., Pichia pastoris. For expressionin Saccharomyces, the plasmid YRp7, for example, (Stinchcomb et al., Nature 282 (1979), 39;Kingsman et al., Gene 7 (1979), 141; Tschemper et al., Gene 10 (1980), 157) is commonly used. This plasmid already contains the TRP1 gene which provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example ATCC No.44076 or PEP4-1 (Jones, Genetics 85 (1977), 12). The presence of the trpl lesion as a characteristic of the yeast host cell genome then provides an effective environment for detecting transformation by growth in the absence of tryptophan.In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is typicallyused as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. Theantibody coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter).Once an antibody molecule of the disclosure has been recombinantly expressed, the wholeantibodies, their dimers, individual light and heavy chains, or other immunoglobulin forms of the present disclosure, can be purified according to standard procedures of the art, including for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigen after Protein A, and sizing column chromatography), centrifugation,differential solubility, e.g. ammonium sulfate precipitation, or by any other standard techniquefor the purification of proteins; see, e.g., Scopes, "Protein Purification", Springer Verlag, N.Y. (1982). Alternatively, a preferred method for increasing the affinity of antibodies of thedisclosure is disclosed in US patent publication 2002-0123057 A1. In one embodimenttherefore, the present disclosure also provides a method for preparing an anti-TTR antibody oran antibody recognizing mutated, misfolded, misassembled or aggregated TTR species and / or fragments thereof or immunoglobulin chain(s) thereof, said method comprising:(a) culturing the host cell as defined hereinabove, which cell comprised a polynucleotide ora vector as defined hereinbefore; and(b) isolating said antibody or immunoglobulin chain(s) thereof from the culture.Furthermore, in one embodiment the present disclosure also relates to an antibody orimmunoglobulin chain(s) thereof encoded by a polynucleotide as defined hereinabove or obtainable by said method for preparing an anti-TTR antibody or an antibody recognizing mutated, misfolded, misassembled or aggregated TTR species and / or fragments thereof or immunoglobulin chain(s) thereof. Pharmaceutical compositions / FormulationsThe present disclosure provides pharmaceutical compositions containing the anti-TTR antibodyand a mixture of the anti-TTR antibody species, respectively, as defined hereinbefore.The pharmaceutical compositions of the present disclosure may be formulated as describedbelow. For example, a pharmaceutical composition containing the anti-TTR antibody may be formulated to include sucrose, polysorbate 80, and histidine. Furthermore, the pharmaceutical composition containing the anti-TTR antibody may be formulated at a desired pH described herein (e.g., pH 5.8). The pharmaceutical composition containing the anti-TTR antibody may further include a pharmaceutically acceptable excipient or diluent, as described herein. For example, the pharmaceutical composition may include the anti-TTR antibody of the presentdisclosure at a concentration of about 50 mg / mL, a histidine buffer with a pH of about 5.8, 6.5%w / v of sucrose, and 0.03 % w / v of polysorbate 80 in a volume of 2.0 mL. In another example, the pharmaceutical composition may include the anti-TTR antibody of thepresent disclosure at a concentration of about 50 mg / mL, a histidine buffer with a pH of about5.8, 8.0% w / v of sucrose, and 0.03 % w / v of polysorbate 80 all in a volume of 2.0 mL. In a preferred embodiment, the antibody comprises a HC chain having the amino acid sequenceset forth in SEQ ID NO: 7, 39 or 9 and a LC having the amino acid sequence set forth in SEQID NO: 8. As shown in Example 2, about 99% to 100% of the antibodies present in the pharmaceutical formulation have a N-terminal pyro-glutamic acid in the heavy chain and about 96% of the antibodies have a loss of the C-terminal lysine. Thus, in one embodiment, about 99% of theantibodies in the formulation of the present disclosure have a heavy chain wherein the N-terminal pyro-glutamic acid is modified from N-terminal glutamine and / or about 96% of the antibodies have a loss of the C-terminal lysine.In a preferred embodiment, the antibody of the present disclosure is composed of two HCshaving an amino acid sequence set forth in SEQ ID NO: 7, and two LCs having an amino acid sequence set forth in SEQ ID NO: 8, and wherein in each HC the glutamine (X1) at the N- terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300, and wherein the amino acids at position X2, X3, X4, and X5 are either modified or unmodified, preferably unmodified. In a further preferred embodiment, the antibody of the present disclosure is composed of two HCs having an amino acid sequence set forth in SEQ ID NO: 39, and two LCs having an amino acid sequence set forth in SEQ ID NO: 8, and wherein in each HC the glutamine (X1) at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine (X7) is absent, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300 (XV), and wherein the amino acids at position X2, X3,X4, and X5 are either modified or unmodified, preferably unmodified, and wherein the amino acids at positions XI, XII, XIII, XIV, XVI, XVI are either modified or unmodified, preferably unmodified.In a further preferred embodiment, the antibody of the present disclosure is composed of twoHCs having SEQ ID NO: 9, and two LCs having SEQ ID: 8, wherein in the HC the glutamine at the N-terminus is modified as pyro-glutamic acid, the C-terminal lysine is lost, i.e., C- terminal lysine is cleaved or absent, respectively, and the heavy chain is N-glycosylated, preferably wherein the N-glycosylation site is at position Asn300. In other words, the antibody is composed of two heavy chains having SEQ ID NO: 12 (preferably wherein the N-terminus is cyclized), and two light chains having SEQ ID NO: 8, and wherein the heavy chain is N- glycosylated, preferably wherein the N-glycosylation site is at position Asn300. In addition, but to a minor extent and preferably in negligible amounts, some antibody species may be found in the analyzed antibody composition that may have undergone other post- translational modifications (PTMs) such as partial cleavage, oxidation, deamidation, succinimide or pyroglutamate formation and isomerization. The PTMs identified to be presentin NI006 / ALXN2220 are referred to in Examples 2 and 3. In particular, next to the above-mentioned C-terminal lysine clipping and cyclization of the N-terminus, the antibody may showmethionine (M) oxidation at HC position 255; asparagine (N) deamidation at HC position 318and / or at HC position 387; asparagine (N) succinimide formation at HC position 318; and / oramidation of the C-terminal proline (P) after the loss of the C-terminal lysine and glycine. Antibody ConcentrationThe antibody of the present disclosure may be formulated into a pharmaceutic compositiondescribed herein at a concentration of about 25 mg / mL to about 150 mg / m (e.g., about 25mg / mL, about 50 mg / mL, about 75 mg / mL, about 100 mg / mL, or about 125 mg / mL), preferablyof about 50 mg / mL to about 100 mg / mL (e.g., about 50 mg / mL, about 55 mg / mL, about 60mg / mL, about 65 mg / mL, about 70 mg / mL, about 80 mg / mL, about 90 mg / mL, about 95mg / mL, or about 100), most preferably 50 mg / mL or 100 mg / mL of the anti-TTR antibody ofthe present disclosure. SucroseThe pharmaceutical composition also includes sucrose, for example, in an amount of about 6%to about 9%, about 6% to about 7%, or about 7.5% to about 8.5% weight per unit volume (w / v) (e.g., about 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, or 9% w / v sucrose). For example, the pharmaceutical composition may include about 6%, 6.1%, 6.2%, 6.3%, 6.4%, 6.45%, 6.5%, 6.55%, 6.6%, 6.7%, 6.8%, 6.9%, 7%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8%, 8.05%, 8.1%, 8.2%, 8.3%, 8.4%, or 8.5% w / v sucrose. In particular, the pharmaceutical composition includes about 6.5% w / v sucrose or about 8% w / v sucrose, most preferably 8% w / v sucrose. PolysorbateThe pharmaceutical composition also includes a polysorbate for example polysorbate 20 orpolysorbate 80, preferably polysorbate 80 (PS80), for example, in an amount of about 0.001% to about 0.1% w / v (e.g., about 0.001%, 0.005%, 0.01%, 0.05% or 0.1% w / v PS(80)). For example, the pharmaceutical composition may include about 0.001%, about 0.002%, about 0.003%, about 0.004%, about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, or about 0.1% w / v PS80. In particular, the pharmaceutical composition includes about 0.03% w / v PS(80). BufferThe pharmaceutical composition also includes a histidine buffer. The pharmaceuticalcomposition may include the buffer in an amount of about, for example, about 1 mM to about100 mM (e.g., about 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 60 mM, 70 mM, 80 mM, mM, 90 mM, or 100 mM). For example, the pharmaceutical may include about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 10 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM, about 19.5 mM, about 20 mM, about 20.5mM, about 21 mM, about 22 mM, about 23 mM, about 24 mM, about 25 mM, about 26 mM,about 27 mM, about 28 mM, about 29 mM, about 30 mM, about 31 mM, about 32 mM, about 33 mM, about 34 mM, about 35 mM, about 36 mM, about 37 mM, about 38 mM, about 39 mM, about 40 mM, about 41 mM, about 42 mM, about 43 mM, about 44 mM, about 45 mM, about 46 mM, about 47 mM, about 48 mM, about 49 mM, about 50 mM, about 51 mM, about 52 mM, about 53 mM, about 54 mM, about 55 mM, about 56 mM, about 57 mM, about 58 mM, about 59 mM, about 60 mM, about 61 mM, about 62 mM, about 63 mM, about 64 mM, about 65 mM, about 66 mM, about 67 mM, about 68 mM, about 69 mM, about 70 mM, about 71 mM, about 72 mM, about 73 mM, about 74 mM, about 75 mM, about 76 mM, about 77 mM, about 78 mM, about 79 mM, about 80 mM, about 81 mM, about 82 mM, about 83 mM, about 84 mM, about 85 mM, about 86 mM, about 87 mM, about 88 mM, about 89 mM, about 90 mM, about 91 mM, about 92 mM, about 93 mM, about 94 mM, about 95 mM, about 96 mM, about 97 mM, about 98 mM, about 99 mM, or about 100 mM. In particular, the pharmaceutical composition includes about 20 mM of histidine, preferably L-histidine and L-histidine monohydrochlorid. pHThe pharmaceutical composition may have a pH of from about 5.0 to about 8.0 (e.g., about 5.5,6.0, 6.5, 7.0, 7.5, or 8.0). For example, the pharmaceutical composition may have a pH of about 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.75, 5.8, 5.85, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0. In particular, the pharmaceutical composition has a pH of about 5.8. Volumes The pharmaceutical composition may be provided (e.g., in a vial or other container, as described herein) in a volume of about 1 mL to about 100 mL, about 1 mL to about 50 mL, about 5 mL to about 25 mL, about 20 mL to about 25 mL, or about 1 mL to about 10 mL (e.g., about 1 mL to about 80 mL, about 1 mL to about 70 mL, about 1 mL to about 60 mL, about 1 mL to about 50 mL, about 1 mL to about 40 mL, about 1 mL to about 30 mL, about 1 mL to about 20 mL, about 1 mL to about 10 mL, about 5 mL to about 20 mL, about 5 mL to about 15 mL, about 5 mL to about 10 mL, about 10 mL to about 20 mL, about 15 mL to about 20 mL, about 20 mL to about 22.5 mL, about 20 mL to about 25 mL, about 1 mL to about 9 mL, about 1 mL to about 8 mL, about 1 mL to about 7 mL, about 1 mL to about 6 mL, about 1 mL to about 5 mL, about 1 mL to about 4 mL, about 1 mL to about 3 mL, about 1 mL to about 2.25 mL, about 1 mL to about 2 mL, or about 2mL to about 2.25 mL). For example, the pharmaceutical composition may be present in a volume of about 1 mL to about 2.25 mL (e.g., about 1 mL to about 2.2 mL, about 1 mL to about 2 mL, about 1 mL to about 1.8 mL, about 1 mL to about 1.6 mL, about 1 mL to about 1.4 mL, about 1 mL to about 1.2 mL, about 1.5 mL to about 1.25 mL, about 1.5 mL to about 2 mL, about 1.9 mL to about 1.2 mL, about 2.1mL to about 2.25 mL) or about 1 mL to about 100 mL (e.g., about 1 mL, about 1.8 mL, about 1.9 mL, about 2 mL, about 2.1 mL, about 2.2 mL about 2.25 mL, about 2.3 mL, about 2.4 mL, about 2.5 mL about 3 mL, about 4 mL, about 5 mL, about 6 mL, about 7 mL, about 8 mL, about 9 mL, about 10 mL, about 20 mL, about 30 mL, about 40 mL, about 50 mL, about 60 mL, about 70 mL, about 80 mL, about 90 mL, or about 100 mL). In a specific example, the pharmaceutical composition may be present in a volume of about 2.25 mL or about 2 mL. In another example, the pharmaceutical composition may be present in a volume of about 20 mL or about 22.5 mL. Additional formulations The pharmaceutical composition may be prepared so that it has not been reconstituted from a lyophilized anti-TTR antibody and / or is not further lyophilized. Also, the pharmaceutical composition may be prepared so that it is essentially free of sodium chloride and / or essentiallyfree of a poloxamer. The pharmaceutical composition can also be prepared as a sterilecomposition. In the most preferred embodiment of the present disclosure, the pharmaceutical compositioncomprises or consist of 50 mg / mL of the antibody of the present disclosure, 20 mM histidine(L-Histidine 1.06 mg / mL and L-Histidine monohydrochloride 2.78 mg / mL), 65 mg / mL or 80 mg / mL sucrose, preferably 80 mg / mL sucrose, 0.3 mg / mL polysorbate 80, and water for infusion / injection at pH 5.8.The disclosure in PCT publication WO2024105092 A1 is incorporated by reference herein inall parts pertinent thereto. CharacteristicsThe disclosure features the disclosure of a pharmaceutical composition with improvedcharacteristics (e.g., stability, solubility, storage, etc.), as described herein (e.g., see Example4). The pharmaceutical composition can be characterized by having a shelf-life of 24 months at2 to 8°C, preferably when protected from light.The pharmaceutical composition of the present disclosure may be characterized by one, two,three or all four stability criteria (i) to (iv) in any combination: (i) the main peak decline (representing the monomer content) under heat stress conditions for 1 month at about 40°C, or for 6 months at about 25°C, or during long-term storage for 18 months at about 5°C is less than 5%, preferably less than 4%, more preferably less than 3%, more preferably less than 2% as measured by SEC-HPLC; (ii) the pharmaceutical composition shows a content of acidic species of the anti-TTR antibody or antigen-binding fragment thereof under heat stress conditions for 2 weeks at about 40°C, or for 3 months at about 25°C of less than or about equal to about 40% as measured by cIEF; (iii) the pharmaceutical composition shows a content of acidic species of the anti-TTR antibody or antigen-binding fragment thereof under long-term storage conditions for 12 months or 18 months at about 5°C of less than 40%, preferably of less than 35% as measured by cIEF; and / or (iv) the anti-TTR antibody or antigen-binding fragment thereof retains binding potency to a TTR protein of at least 80%, preferably of at least 90% after storage for 6 months at about 25°C, or after storage for 12 months or 18 months at about 5°C as measured by ELISA and relative to a control (e.g., without prolonged storage). Preferably, the pharmaceutical composition shows any one or all of the characteristics as set forth in the Tables of Example 4. In particular, the pharmaceutical composition has an osmolality of ≥ 240 mOsm / Kg. The pharmaceutical composition is stable upon freezing and thawing. As used herein, the term “stable” or “stability”, as used in the context of a pharmaceutical composition described herein, refers to the maintenance of the physical and functional characteristics of the composition over time. For example, a stable composition may be described as one that retains its appearance (e.g., color, opalescence, number of visible particles, and / or number of subvisible particles), pH, antibody concentration, and / or osmolarity after long term storage.The pharmaceutical composition of the present disclosure has been shown to remain stable at40 ± 2 °C and 75 ± 5% RH for at least 1 month (stress stability studies); at 25 ± 2 °C / 60 ± 5% RH for at least 6 months (accelerated stability studies); and / or at 5 ± 3 °C for at least 12 monthsto 18 months (long-term stability studies). Furthermore, the extinction coefficient of thepharmaceutical composition has been determined to be 1.438 (mg / mL)-1cm-1and the pharmaceutical formulation has been shown to be a sterile, colorless to slightly yellow, clear to slightly opalescent solution, essentially free of visible particles with a pH of 5.8. Methods of Treatment The antibody of the present disclosure, the polynucleotide(s) of the present disclosure, the vector(s) of the present disclosure, the host cell of the present disclosure, or the compositionsof the present disclosure, containing the anti-TTR antibody of the present disclosure can beused in the prophylactic or therapeutic treatment of a disease associated with TTR amyloidosis, such as ATTR, e.g., ATTR-CM, ATTR polyneuropathy(ATTR-PN), Familial Amyloid Polyneuropathy (FAP), Familial Amyloid Cardiomyopathy (FAC), Senile Systemic Amyloidosis (SSA), systemic familial amyloidosis, leptomeningeal / Central Nervous System (CNS) amyloidosis including Alzheimer disease, TTR-related ocular amyloidosis, TTR-relatedrenal amyloidosis, TTR-related hyperthyroxinemia, TTR- related ligament amyloidosisincluding carpal tunnel syndrome, rotator cuff tears and lumbar spinal stenosis, andpreeclampsia. Furthermore, the antibody of the present disclosure can be used in in vivodetection or imaging of or targeting a therapeutic and / or diagnostic agent to TTR in the human or animal body, preferably wherein said in vivo imaging comprises scintigraphy, positron emission tomography (PET), single photon emission tomography (SPECT), near infrared (NIR), optical imaging or magnetic resonance imaging (MRI). In particular, the pharmaceutical compositions described herein can be used in a method oftreating or preventing transthyretin-mediated amyloidosis (ATTR). Additionally, thepharmaceutical compositions described herein can be used in a method of treating or preventing ATTR amyloidosis with cardiomyopathy (ATTR-CM, such as WT-ATTR-CM). For example, a pharmaceutical composition containing a human anti-TTR antibody of the present disclosure at a concentration of about 50 mg / mL, a histidine buffer with a pH of about 5.8, 6.5% or 8.0% w / v of sucrose, and 0.03 % w / v of polysorbate 80 can be administered to treat ATTR or ATTR- CM, such as WT-ATTR-CM. The pharmaceutical composition containing the anti-TTR antibody can be administered to a human subject to treat, prevent, or control transthyretin-mediated amyloidosis (ATTR), including ATTR amyloidosis with cardiomyopathy (ATTR-CM, such as WT-ATTR-CM). Thepharmaceutical composition is preferably be administered by intravenous injection or infusionThe composition and methods provided herein may be used to treat a subject that has ATTR, ATTR-CM, ATTR polyneuropathy (ATTR-PN), Familial Amyloid Polyneuropathy (FAP), Familial Amyloid Cardiomyopathy (FAC), Senile Systemic Amyloidosis (SSA), systemic familial amyloidosis, leptomeningeal / Central Nervous System (CNS) amyloidosis, Alzheimer disease, TTR-related ocular amyloidosis, TTR-related renal amyloidosis, TTR-related hyperthyroxinemia, TTR-related ligament amyloidosis, carpal tunnel syndrome, rotator cuff tears, lumbar spinal stenosis, preeclampsia, or a known pathogenic TTR mutation (e.g., one that causes amyloidosis). The subject may have sporadic, WT-ATTR-CM and a negative genetic testing for a TTR mutation. The pharmaceutical composition may be ready-to use for administration to a subject in need thereof, preferably via intravenous infusion. The pharmaceutical composition may be dilutedprior to infusion in glucose or a polymer thereof, preferably wherein the polymer is dextran.The concentration of glucose or a polymer thereof may be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% w / v, preferably in 5% glucose. Containers Provided herein are also containers comprising the pharmaceutical composition of the disclosure. Suitable containers include, for example, bottles (e.g., infusion bottles), vials (e.g., a Type I clear glass vial), syringes, IV solution bags, etc. The containers may be formed froma variety of materials such as glass or plastic. The container may have a sterile access port (forexample, the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle) Containers, such as Type I clear glass vials or infusion bottles, may be 1 mL, 2 mL, 5 mL, 10 mL, 15 mL, 20 mL, or 25 mL in size and capable of accommodating about a 10% to about 15% (e.g., 10% or 12.5%) volume overfill of the pharmaceutical composition. The container may include a volume of a pharmaceutical composition described herein, such as a volume of, e.g., 0.5 mL to 10 mL, 2 mL to 2.25 mL, 10 mL to 20 mL, 15 mL to 25 mL, 20 mL to 22.5 mL, e.g., 0.5 mL, 1 mL, 2 mL, 2.25 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, 15 mL, 16 mL, 17 mL, 18 mL, 19 mL, 20 mL, 20.5 mL, 21 mL, 21.5 mL, 22 mL, 22.5 mL, 23 mL, 24 mL, or 25 mL. In a preferred embodiment, the pharmaceutical composition, i.e., the drug product described herein is provided as a concentrate for solution for infusion that is presented as sterile, colorless to slightly yellow, clear to slightly opalescent liquid, essentially free of visible particles and supplied in a 2 mL (2R) glass vial with an aluminum flip-off cap over a 13 mm rubber stopper. The product is preferably diluted in sterileglucose before administration, which is a commercial product and in one embodiment notaccompanying the drug product. Preferably, the container is a 2 ml or 20 ml vial and most preferably, a glass vial with an aluminum flip-off cap over a 13 mm rubber stopper, which preferably contains an approximate 12.5% volume overfill, or a total volume of 2.25 ml or 22.5 ml of the pharmaceutical formulation. Articles of Manufacture / Therapeutic kitsThe present disclosure also provides an article of manufacture (e.g., a kit, and in particular atherapeutic kit) containing materials useful for the treatment or prevention of transthyretin- mediated amyloidosis (ATTR) in a human subject. The article of manufacture includes one ormore (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 7, 48, 4950, or50 or more) containers of the disclosure as described hereinbefore and a label or package inserton or associated with the one or more container, wherein the container comprise the composition of the present disclosure. The label or package insert indicates that the composition is used for treating ATTR. The articleof manufacture may include at least a first container with the pharmaceutical compositionOptionally, the article of manufacture may further include a second container with a second therapeutic agent, like a TTR tetramer stabilizer, for example tafamidis. The article of manufacture in this embodiment of the disclosure may further include a package insert indicating that the compositions can be used to treat ATTR. Alternatively, or additionally, the article of manufacture may further include a second (or third) container including a pharmaceutically acceptable buffer, such as BWFI, PBS, Ringer’s solution, and dextrose solution.The article of manufacture may further include other materials desirable from a commercialand user standpoint, including other buffers, diluents, filters, needles, and syringes. For example, the article of manufacture (e.g., a kit) may include a second container with a pharmaceutically acceptable buffer, such as phosphate-buffered saline, Ringer’s solution, and / or a glucose or a polymer thereof, such as dextran (e.g., at a concentration of about 5% w / v). The article of manufacture may include other materials, including buffers, diluents, filters, needles, syringes, and package inserts with instructions for use. In a preferred embodiment, the article of manufacture includes vials, preferably clear glass vials sealed with a (grey) rubber stopper and a (blue) aluminum-plastic cover flip-off cap. Preferably, the antibody is presented in vials at a concentration of 50 mg / mL and is provided as a concentrate for solution for infusion that is presented as sterile, colorless to slightly yellow, clear to slightly opalescent liquid, essentially free of visible particles. In a further preferred embodiment, the article of manufacture includes a dosing syringe in a dosing pump or an infusion bag comprising the diluted antibody formulation. Live-cell imaging methods of the present disclosure Due to the findings made during the experiments performed within the scope of the present invention, methods for screening, validation, characterization, and quality control of an amyloid depleting drug have been developed. In particular, the method of validating an amyloid depleting drug, the screening method of identifying and optionally obtaining an amyloid depleting drug from a plurality of testcompounds, the method of analyzing the impact of an agent, such as a second drug on theamyloid depleting activity of the amyloid depleting drug, and the screening of an amyloid depleting drug for its capability to bind to amyloid, and to mediate macrophage recruitment to amyloid deposits, followed by amyloid fragmentation and internalization, all comprise the stepsof incubating tissue sections comprising amyloid deposits with macrophages in the presence ofthe amyloid depleting drug or a test compound in case of the screening method and performinghigh-resolution live-cell imaging. The live-cell imaging uses refractive index imaging for cell visualization and fluorescence microscopy for amyloid imaging. Accordingly, either the tissuesections are stained with an amyloid specific fluorescent dye which results in the staining of theamyloid deposits in the tissue sections; the amyloid depleting drug and the test compound, respectively, is labeled with a fluorescent dye, which results in labeling of the amyloid depositsin the tissue sections upon binding of the amyloid depleting drug and the test compound,respectively, to the amyloid; or the tissue sections are stained with an amyloid specific dye andthe amyloid depleting drug and the test compound, respectively, is labelled.In one embodiment, the tissue sections are stained with an amyloid specific fluorescent dyebefore addition of the macrophages and the amyloid depleting drug (or in case of the screeningmethod, a test compound), and the amyloid depleting drug and the test compound, respectively,is labeled with a fluorescent dye, wherein this approach is preferably used for visualizing anddetecting the binding of the amyloid depleting drug and the test compound, respectively, to theamyloid deposits via generating an overlap image of the fluorescence signal of the amyloiddepleting drug and the test compound, respectively and the fluorescence signal emitted by theamyloid specific fluorescent dye. In this embodiment, the amyloid depleting drug and the test compound, respectively, is labeled with a fluorescent dye which is different from the fluorescent dye used to stain the amyloid deposits. In one embodiment, the tissue sections are stained with an amyloid specific fluorescent dyebefore addition of the macrophages and the amyloid depleting drug and the test compound,respectively, and the amyloid depleting drug and the test compound, respectively, is not labelled, wherein this approach is preferably used to visualize and determine macrophagemediated internalization of amyloid via detecting intracellular fluorescence signal in phagocyticvesicles. Such a fluorescence signal is usually a punctuate fluorescence signal.In one embodiment, the amyloid depleting drug and the test compound, respectively, is labeledwith a fluorescent dye and the tissue sections are not stained before addition of the macrophagesand the amyloid depleting drug and the test compound, respectively, wherein this approach ispreferably used to visualize and determine macrophage mediated amyloid fragmentation viadetecting the successive separation of a fluorescence signal, preferably a punctuate fluorescencesignal, from the fluorescence signal of the amyloid deposit, which is generated via binding ofthe labelled amyloid depleting drug and the test compound, respectively, to the amyloid deposit. In principle any fluorescent dye can be used in the methods of the present invention, which is either suitable for staining amyloid, i.e., an amyloid specific fluorescent dye, or suitable to label a drug. In a preferred embodiment, the amyloid depleting drug and the test compound, respectively is labelled with the fluorescent dye Vivotag-680. In addition, or alternatively, theamyloid deposits are preferably stained with the amyloid specific dye Amytracker 680 or anyother Amytracker variant, for example Amytracker 480, 520, 540, or 630. Alternatively,Thioflavin T staining can be performed.In one embodiment, live-cell imaging is performed with the Nanolive CX-A instrument usingrefractive index imaging for cell visualization and fluorescence microscopy (Cy5 channel) foramyloid imaging. The Nanolive CX-A is preferably placed in a temperature-controlled roomand installed on an anti-vibration table. During imaging, the cell culture dishes comprising the tissue sections were maintained at 37°C with controlled humidity and 5% CO2 supply.Preferably, imaging frequency is every 15 min and experiment duration is preferably about 20hours. Thus, with the help of high-resolution live-cell imaging, binding of the amyloid depleting drug and the test compound, respectively, to the amyloid deposit can be observed as well asmacrophage recruitment to amyloid deposits leading to internalization and fragmentation of theamyloid and amyloid deposit, respectively, which is followed by intracellular degradation ofthe amyloid. If any one of (a) binding of the amyloid depleting drug and the test compound, respectively, to the amyloid, (b) amyloid internalization, and (c) amyloid fragmentation is observed in the method of the present invention, this verifies that the amyloid depleting compound has indeed amyloid depleting activity and that the test compound has amyloid depleting activity, respectively. Preferably, if (b) amyloid internalization or (c) amyloid fragmentation is observed, this indicates that the amyloid depleting compound has indeed amyloid depleting activity and that the test compound has amyloid depleting activity, respectively. More preferably, if (b) amyloid internalization and (c) amyloid fragmentation is observed, this indicates that the amyloid depleting compound has indeed amyloid depleting activity and that the test compound has amyloid depleting activity, respectively. More preferably, if (a) binding of the amyloid depleting drug and the test compound, respectively, to the amyloid, and (b) amyloid internalization, and (c) amyloid fragmentation is observed, this indicates that the amyloid depleting compound has indeed amyloid depleting activity and that the test compound has amyloid depleting activity, respectively. The methods of the present invention employ macrophages. Macrophages are immune cells that originate from embryogenesis or from the differentiation of monocytes. They can adopt numerous phenotypes depending on their origin, tissue distribution and in response to different stimuli and tissue environment. Thus, in vivo, macrophages are endowed with a continuum of phenotypes that are rarely strictly pro-inflammatory or anti-inflammatory and exhibit a broad expression profile that sweeps over the whole polarization spectrum. Schematically, three main macrophage subpopulations coexist in human tissues: naïve macrophages also called M0, pro- inflammatory macrophages referred as M1 macrophages, and anti-inflammatory macrophages also known as M2 macrophages. Naïve macrophages display phagocytic functions, recognize pathogenic agents, and rapidly undergo polarization towards pro or anti-inflammatory macrophages to acquire their full panel of functions. Pro-inflammatory macrophages are widely involved in inflammatory response, during which they exert anti-microbial and anti-tumoralfunctions. By contrast, anti-inflammatory macrophages are implicated in the resolution ofinflammation, the phagocytosis of cell debris and tissue reparation following injuries. Macrophages also play important deleterious or beneficial roles in the initiation and progressionof different pathophysiological settings including solid and hematopoietic cancers. In principel,any kind of macrophage can be used as long as they are able to perform phagocytosis on amyloidogenic proteins.As described in Example 5, macrophages were generated by differentiation of THP1 cells andthus, in a preferred embodiment, the macrophages used in the methods of the present inventionare THP1 cell-derived macrophages. In a preferred embodiment, the macrophages weregenerated by differentiation of THP1 cells with phorbol 12-myristate-13-acetate (PMA), whichis preferably used at a concentration of at 100 ng / mL and wherein incubation was preferablyperformed for 3 days, preferably followed by 3 days of rest without PMA. Macrophages arepreferably distributed to the tissue sections at a density of 400000 cells in the presence of theamyloid depleting drug. If the amyloid depleting drug to be analysed is an antibody, preferably an anti-TTR antibody and most preferably the anti-TTR antibody as defined hereinbefore, the antibody is preferably used at a concentration of 10 nM (1.5 ug / mL). This concentration was previously identified as triggering maximum antibody-dependent phagocytosis of ATTR aggregates by macrophages in vitro. The amyloid depleting drug, also referred to as amyloid depleting compound is any compound which is capable to remove or reduce amyloid from tissue, preferably via recruitment of macrophages which internalize and degrade the amyloid. In a preferred embodiment, the compound is an anti-amyloid antibody. This mechanism of action is also referred to as antibody-dependent cell-mediated phagocytosis (ADCP). It is defined as a highly regulatedprocess by which antibodies eliminate targets via connecting its Fc domain to specific receptorson phagocytic cells and eliciting phagocytosis. In the context of the present invention, ADCP refers to the mechanism(s) by which Fc receptors of phagocytic cells (here the macrophages) bind to the amyloid depleting drug, e.g., anti-amyloid antibodies that are bound to the amyloid and stimulate the phagocytic cells to internalize the protein and the cyclic compound,respectively. Accordingly, the amyloid depleting drug is preferably an antibody or a fragmentor derivative thereof comprising an Fc domain or an antibody fragment fused to domain whichis able to induce phagocytosis, like an Fc domain. The suitability of the live-cell imaging method has been verified with tissue sections comprising TTR amyloid and with an anti-TTR antibody, in particular with the anti-TTR antibody ALXN2200 as described hereinbefore. Thus, the amyloid depleting drug is preferably an anti- TTR antibody, most preferably the anti-TTR antibody as defined hereinbefore, which is capale to deplete amyloid TTR, wherein the TTR is wildtype or mutated TTR, preferably wildtype TTR. However, it is prudent to expect that the methods of the present invention can not only be used for the validation, screening, quality control, characterization, etc. of an anti-TTR antibody, but also for the validation, screening, quality control, characterization, etc. of any compound which is able to deplete TTR amyloid by recruitment of macrophages and phagocytosis, respectively. Furthermore, since macrophage mediated depletion of amyloid is not restricted to the depletion of TTR amyloid, the methods can be applied to any amyloid depleting compound, for example to compounds depleting amyloidogenic α-synuclein (α-syn), tau, prion protein (PrP), amyloid beta (Aβ), β2-microglobulin (β2-m), Immunoglobulin light chain (LC), Immunoglobulin heavy chain (HC), serum amyloid A (SAA), amylin (IAPP), Chromosome 9 open reading frame 72(C9orf72), TAR DNA-binding protein 43 (TDP-43), superoxide dismutase 1 (SOD1), RNA-binding protein fused in sarcoma (FUS), huntingtin (htt), optineurin (OPTN), neuroserpin, ABri, Adan, ubiquilin,optineurin, leucocyte chemotactic factor 2 (LECT2), gelsolin, apolipoprotein AI (ApoAI), apolipoprotein AII (ApoAII), apolipoprotein AIV (ApoAIV), apolipoprotein CII (ApoCII), apolipoprotein CIII (ApoCIII), fibrinogen, cystatin C, and lysozyme. Further amyloid fibril-forming proteins can be derived from AmyPro, an open- access database providing a collection of amyloid fibril-forming proteins (Varadi et al., Nucleic Acids Research 46 (2018), D387–D392, DOI: 10.1093 / nar / gkx950), and / or can be those listed in Table 1 of Benson et al., Amyloid 25 (2018), 215–219. In a preferred embodiment, the amyloidogenic protein is involved in systemic amyloidosis, and more preferably selected from the following list: transthyretin (TTR), in particular wild type TTR and variant TTR, preferably wild type TTR, immunoglobulin light chain (LC), immunoglobulin heavy chain (LH), serum amyloid A (SAA), leucocyte chemotactic factor 2 (LECT2), gelsolin, apolipoprotein AI (ApoAI), apolipoprotein AII (ApoAII), apolipoprotein AIV (ApoAIV), apolipoprotein CII (ApoCII), apolipoprotein CIII (ApoCIII), fibrinogen, ^2microglobulin, in particular wild type and variant ^2 microglobulin, cystatin C, ABriPP, prionprotein, and lysozyme; see for example Benson et al., Amyloid 25 (2018), 215–219 and Muchtar et al., Journal of Internal Medicine 289 (2021), 268-292. The tissue section is preferably a section of cardiac tissue, kidney tissue, liver tissue, gastro- intestinal tissue, skin tissue, muscle tissue, tongue tissue, fat tissue, salivary gland tissue, lymph node tissue, brain tissue, pancreatic tissue or any amyloidoma. In a preferred embodiment, thetissue section is a cardiac tissue section. Most preferably, the tissue sections are obtained froma subject suffering from an amyloidosis or amyloid-related disease, preferably form TTRamyloidosis, most preferably of cardiac TTR amyloidosis. The tissue sections obtained fromthe patient are tissue sections which comprise the amyloid deposit.The methods of the present invention can also comprise the analysis of a control compound,which is for example an isotype control antibody, in particular if the amyloid depletingcompound is an antibody. This ensures that the observed effect, i.e., the (a) binding of theamyloid depleting drug and the test compound, respectively, to the amyloid, (b) amyloid internalization, and (c) amyloid fragmentation is observed in the method of the presentinvention, is attributed to the action of the amyloid depleting drug and not any unspecific sideeffect. As mentioned above, in a preferred embodiment, an amyloid depleting drug is analyzed which is suitable for TTR amyloid depletion and thus, suitable for the treatment of transthyretin (TTR) amyloidoses or a TTR amyloid-related disease, preferably cardiac TTR amyloidosis.As shown in Example 5, the mechanism of action of an ATTR-specific antibody has beenanalyzed and the antibody has been shown to bind to the amyloid in tissue sections, and toinduce macrophage mediated amyloid internalization and fragmentation. Accordingly, in oneembodiment of the method of the present invention, the drug comprises an anti-amyloid proteinantibody or amyloid binding molecule. In a further embodiment, the drug is an antibody, andthe control is a corresponding isotype control antibody. Suitable antibody candidates are knownfrom the prior art, e.g. anti-transthyretin (TTR) antibodies are disclosed in WO 2015 / 092077A1, WO 2014 / 124334 A2, WO 2018 / 007923 A3, WO 2016 / 120810 Al, US 2017 / 0058023 A1and US 9,879,080 B2. Of course, it is envisioned within the present invention that especially novel antibodies or compounds in general may be applied to the method of the present inventionin order to be assessed for their suitability as amyloid depleting drugs. Besides antibodies, alltypes of drugs may conveniently be tested by the method of the present invention for theirsuitability as anti-amyloid drugs as long as they are able to recruit macrophages.Thus, the method the present invention enables obtaining and selection of amyloid depletingcompounds, in particular antibodies which can be reasonably expected to be as specific as to selectively bind to the target amyloid protein in the patient to be treated at the desired andnecessary location of the for example toxic amyloid deposits and mediate the depletion of theamyloid. In a particularly preferred embodiment, the candidate antibody is a humanized, human-like or human antibody, preferably a human-derived antibody, most preferably isolated from human memory B cells, and recombinant variants thereof, which typically substantially comprise the variable heavy and light chain of the original human-derived antibody and a human constant domain which is preferably of the IgG1 or IgG4 subtype but not necessarily identical with the constant domain of the original human-derived antibody. A further aspect of the present invention relates to a process for the manufacture of a pharmaceutical composition which comprises an amyloid depleting drug and a pharmaceutically acceptable carrier. In this process, the amyloid depleting drug that has been determined to be a suitable amyloid depleting drug by the method of the present invention as described, supra, is mixed with a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers and administration routes can be taken from corresponding literature known to the person skilled in the art. The pharmaceutical compositions of the present invention can be formulated according to methods well known inthe art; see for example Remington: The Science and Practice of Pharmacy (2000) by theUniversity of Sciences in Philadelphia, ISBN 0-683-306472, Vaccine Protocols. 2nd Edition byRobinson et al., Humana Press, Totowa, New Jersey, USA, 2003; Banga, Therapeutic Peptidesand Proteins: Formulation, Processing, and Delivery Systems. 2nd Edition by Taylor andFrancis. (2006), ISBN: 0-8493-1630-8. Examples of suitable pharmaceutical carriers are well known in the art and include phosphate buffered saline solutions, water, emulsions, such as oil / water emulsions, various types of wetting agents, sterile solutions etc. Compositions comprising such carriers can be formulated by well-known conventional methods. These pharmaceutical compositions can be administered to the subject at a suitable dose. Administration of the suitable compositions may be effected by different ways. Examples include administering a composition containing a pharmaceutically acceptable carrier via oral, intranasal, rectal, topical, intraperitoneal, intravenous, intramuscular, subcutaneous, subdermal, transdermal, intrathecal, and intracranial methods. Aerosol formulations such as nasal spray formulations include purified aqueous or other solutions of the active agent with preservative agents and isotonic agents. Such formulations are preferably adjusted to a pH and isotonic state compatible with the nasal mucous membranes. Pharmaceutical compositions for oral administration, such as single domain antibody molecules (e.g., "nanobodies™") etc are also envisaged in the present invention. Such oral formulations may be in tablet, capsule, powder, liquid or semi-solid form. A tablet may comprise a solid carrier, such as gelatin or an adjuvant. Formulations for rectal or vaginal administration may be presented as a suppository with asuitable carrier; see also O'Hagan et al., Nature Reviews, Drug Discovery 2(9) (2003), 727-735. Further guidance regarding formulations that are suitable for various types of administration can be found in Remington's Pharmaceutical Sciences, Mace Publishing Company, Philadelphia, PA, 17thed. (1985) and corresponding updates. For a brief review ofmethods for drug delivery see Langer, Science 249 (1990), 1527-1533. Preferred carrier inaccordance with the present invention are buffers, a tonicity agents and / or a surfactants, mostpreferably all three components. In one embodiment of the process of the present invention, the pharmaceutical composition is designed for the treatment of an ATTR or ATTR-related disease. Thereby, the amyloidosis is characterized by the ATTR deposit in the patient, and especially the respective precursorprotein. Most preferably, the pharmaceutical composition is a pharmaceutical compositioncomprising the amyloid depleting drug, in particular the anti-amyloid antibody, most preferablythe anti-TTR antibody as defined hereinbefore in an aqueous formulation as definedhereinbefore. In another aspect, the present invention relates to a method for characterization, validation, development and / or quality control, which also included batch control, of an amyloid depletingdrug, which is suitable for the treatment of an amyloidosis or amyloid-related disease. Forexample, an amyloid depleting drug is characterized in the live-cell imaging method and theinformation about the drug that has been subjected to the method of validating an amloiddepleting drug of the present invention as described, supra, is communicated to a client,contracting party or cooperation partner. Furthermore, the drug that has been determined to bea suitable amyloid depleting drug may be selected, and optionally the amyloid depleting drugor a pharmaceutical composition comprising the amyloid depleting drug is used for thetreatment of an amyloidosis or amyloid-related disease. The method of the present invention may be performed in addition to another method useful for verifying the therapeutic applicability of a candidate drug and / or useful to detect the capability of a drug to deplete amyloidogenic proteins and amyloid deposits, respectively. Such a method is for example a method employing the patient-derived amyloid xenograft (PDAX)non-human animal model as disclosed in WO 2020 / 094883 A1, which content is hereinincorporated by reference. Examples The following examples of specific aspects for carrying out the present disclosure are offered for illustrative purposes only and are not intended to limit the scope of the present disclosure in any way. Example 1. Cloning and Expression of NI006 / ALX2220NI006 / ALXN2220 is produced in the CHO K1 cell line (ATCC No. CCL 61).Construction of Expression Plasmids and Sequence ConfirmationFirst, signal peptides were added to the sequences encoding the heavy chain gene (set forth inSEQ ID NO: 15) and light chain gene (set forth in SEQ ID NO: 16) of NI006 / ALXN2220 and each expression cassette (heavy chain gene including signal peptide and light chain including signal peptide) was cloned into an individual expression vector. The expression vectors comprise typical elements, like a promoter to control gene expression, a ribosome entry site, two selectable markers, one for maintenance in mammalian cells and one for maintenance in E. coli, a terminator, and a replication origin for propagation in E. coli.The CHO K1 host cell line was thawed and cultured before used for transfection. The linearizedlight and heavy chain expression vectors were transfected with a ratio of 1:1 into the CHO-K1host cell line using Freestyle Max reagent.48 hours after transfection, cells were plated in four96-well plates in selection media comprising the corresponding antibiotics for maintenance inmammalian cells. The 96-well plates were incubated in a static CO2 incubator (36.5 °C, 6%CO2) for 2 to 3 weeks with media change every 3 to 4 days. Afterwards, single clones were tested, a master cell bank (MCB) was prepared. Example 2. Characterization of mature NI006 / ALXN220Antibody NI006 / ALXN2220 was produced in the CHO-K1 cell line (ATCC No. CCL 61) asdescribed in Example 1 and obtained from the cell culture. The amino acid sequence ofNI006 / ALXN2220’s mature heavy chain (HC) and light chain (LC) is set forth in SEQ ID NOs:7 and 8, with the below-mentioned modifications. The total number of amino acids, number ofamino acids of the heavy chain, and number of amino acids of the light chain are 1328, 450, and 214, respectively. Further characterization of antibody NI006 / ALXN2022 was mainly performed by standard procedures, for example by mass spectroscopy analysis. For example, liquid chromatography with tandem mass spectrometry (LC-MS / MS) analysis of fragments of NI006 / ALXN2220 obtained from Lys-C and trypsin sequential digestion as well as free sulfhydryl analysis was used to identify post-translational modifications of NI006 / ALXN2220. The characterization of antibody-based therapeutics via LC-MS analysis is a standard procedure and can be performed by a skilled artisan; see for example Robotham and Kelly, Approaches to the Purification, Analysis and Characterization of Antibody-Based Therapeutics (2020), 1-33. Exemplary Released N-Glycan Method for determination of glycosylation profile: Glycan method is used to profile N- N-glycans of ALXN2220 are released using PNGase F and labeled with 2-AB, followed by HILIC (Hydrophilic Interaction Chromatography) separation and fluorescence detection (FLD) with a UPLC system. Individual N-glycans are quantified by their peak area percentages relative to the total peak area. Exemplary Peptide Mapping Studies using LCMS: Analysis of the primary structure and post-translational modifications is accomplished by peptide mapping with high resolution mass spectrometry (MS). ALXN2220 is reduced, denatured, and alkylated. Reduced and alkylated protein undergoes sequential digestion with endoproteinase Lys-C / trypsin. The resulting digested peptides are separated by reversed phase C18 column followed by detection with high resolution mass spectrometer. The identity of thepeptides is confirmed against the theoretical mass of the peptides and MS / MS. Post-translational modification is quantitated by the peak area percentages of the modified peptide relative to the sum of the peak area of modified and unmodified form of the peptide. Exemplary icIEF Method (charge method) for determining charge variants: Imaging Capillary Isoelectric Focusing (iCIEF) is used to separate charge variants of protein based on their isoelectric points (pI). Samples are prepared by mixing with master mixture composed of pharmalytes, pI markers, urea, and water. ALXN2220 is separated into main peak, acidic region, and basic region through a pH gradient formed by carrier ampholytes inside the capillary, separating the isoforms according to their isoelectric points. The focused protein zones are detected by whole-capillary UV detection. Acidic, main, and basic species are quantified by their peak area percentages relative to the total of all protein peak detected. The molecular weight of antibody NI006 / ALXN2220 as determined by standard mass spectroscopy is approximately 147.1 kDa for the intact IgG1 and 144.2 kDa for thedeglycosylated variant. The pI of antibody NI006 / ALXN2220 is 8.4 (theoretical) and 9.3(experimentally determined). The Theoretical Extinction Coefficient (A0.1%) (mL / (mg * cm))of antibody NI006 / ALXN2220 is 1.390 (theoretical) and 1.438 (experimentally determined).The monoclonal antibody NI006 / ALXN2220 is an IgG1 subclass antibody, which is composed of two heavy chains of the IgG1 subclass and two light chains of the kappa subclass. The four chains are stabilized by multiple disulfide bonds. In particular, as determined by standardprocedures, i.e., per Lys-C and trypsin digestion and subsequent LC-MS, at least the followingdisulfide bridges are present in NI006 / ALXN2220: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324 HC:C370-HC:C428 NI006 / ALXN2220 is a glycoprotein, and the constant region of each heavy chain contains one N-linked glycan site at residue N300. During determination of the glycosylation profile, it was shown that the major N-glycan types are G0F (~49.0%) and G1F (~25.4%). In more detail, the following glycosylation profile (the types of sugar, the location of glycosylation site(s), etc.) has been determined for NI006 / ALXN2220:Glycan Glycan Type23100 Man3+1F33000 G0-GN33100 G0F-GN43000 G043100 G0F25000 Man534100 / 44000 G1F-GN / G1a44000 G1b44100 G1Fa44100 G1Fb45100 G2F45110 G2FS145120 G2FS2 The nomenclature of the glycans follows the order of HexNac-Hexose-Fucose-NeuAc-NeuGc. For example, 23000 is HexNac(2)-Hexose(3)-Fucose(0)-NeuAc(0)-NeuGc(0). G1Fa and G1Fb are isomers and are grouped into G1F. G1F is calculated as the sum of G1Fa and G1Fb using the original unrounded numbers. The glycosylation profile is depicted in Figure 6 and the abundance of the different glycans in11 separate batches of NI006 / ALXN2220 is listed in Table 2.Table 2. Relative abundance of glycans (in %) Total Sum Major Sum Mannose BatchIdentified FucosylatedGalactosylatedFucosylatedMan5(Man5+Man31F) SiaylatedUnknown1* 98.6 89.1 37.4 81.8 3.4 3.6 1.1 1.42** 98.9 90.9 33.6 85.4 1.8 1.9 0.9 1.13** 98.6 91.8 29.1 85.9 2.4 2.5 0.7 1.44** 99.2 90.7 31.4 85.5 1.9 2.0 0.8 0.85** 98.3 90.1 31.0 84.6 1.9 2.1 0.7 1.76** 98.0 89.8 29.4 84.6 1.8 2.0 0.6 2.07** 98.4 89.8 32.9 84.3 1.9 2.1 0.8 1.68** 98.2 91.4 29.7 86.1 1.4 1.6 0.8 1.89** 98.0 90.6 31.7 84.9 1.7 1.9 0.8 2.010** 99.3 93.3 27.4 89.1 1.3 1.4 0.7 0.711** 97.1 89.6 26.6 85.2 1.6 1.7 0.7 2.9* 0.2 pH dead band (see Example 3)**0.05 pH dead band (see Example 3)The glycosylation profile has been determined using N-glycan method. Peptide mapping has been carried out using LCMS. Furthermore, glutamine at N-terminal modified as pyro-glutamic (abundance in sample: 99.9) acid and C-terminal lysine clipping of the heavy chain (abundance in sample: 95.8%) have been identified as the major post-translational modifications. In addition, small ratio modifications, such as methionine oxidation, asparagine deamidation and asparagine succinimide formation,have been experimentally determined, (e.g., using LCMS-based methods) and further predictedas shown in Tables 3 and 4: Table 3. Experimentally determined PTMsNo. Seq. No. Location Sequence SEQPTMs ID NO.*1 HC: 1-13 Q1 QLQLQESGPGLVK 25 pE(Q)2 HC: 46-66 58N / T59 GLEWIGGIYHSGNTYDNPSLK 26 Clipping (N / T)3 HC: 46-66 N58 GLEWIGGIYHSGNTYDNPSLK 26 Deamidation(N)4 HC: 69-77 M71 LTMSVDTSK 27 Oxidation (M)5 HC: 100-124 M115 IVPGGDAFDIWGQGTMVTVSSASTK 28 Oxidation (M)6 HC: 252-258 M225 DTLMISR 29 Oxidation(M)7 HC: 278-291 D283 FNWYVDGVEVHNAK 30 Isomerization(D)8 HC: 296-304 N300 EEQYNSTYR 31 Glycosylation(N)9 HC: 305-320 N318 VVSVLTVLHQDWLNGK 32 Deamidation(N) N318 VVSVLTVLHQDWLNGK 32 SuccinimideFormation(N)10 HC: 359-363 M361 EEMTK 33 Oxidation (M)11 HC: 374-395 N387 GFYPSDIAVEWESNGQPENNYK 34 / Deamidation(N) N387 GFYPSDIAVEWESNGQPENNYK 34 SuccinimideFormation(N)12 HC: 420-442 M431 WQQGNVFSCSVMHEALHNHYTQK 35 Oxidation (M)#13 HC: 443-450 K450 SLSLSPGK 36 -KP448 SLSLSPGK 36 -K -GAmidation(P)Note: HC refers to heavy chain and LC refers to light chain. Peptide sequences in underlinedfont were identified as the site of the PTMs. * refers to N-terminal related peptide of heavychain and # refers to C-terminal related peptide of heavy chain. pE(Q) refers to the N-terminalglutamine modified as pyro-glutamic acid. -K refers to loss of the C-terminal lysine. -K -GAmidation(P) refers to the amidation of the C-terminal proline after the loss of the C-terminal lysine and glycine.Table 4. Predicted PTMsPost translational Amino acid(s) Light Chainb H b caeavy Chain Totalmodification (PTM) Site Pyroglutamic acid Q 0 1 (Q1) 25 (M71, M115, M1 (M4)M255, M361, 12 M431) 9 (W36, W38, Oxidation W49, W110, 2 (W35, WdW161, W280, 22 W148) W316, W384, W420) NG 0 2 (N318, N387) 4NS 1 (N158) 2 (N162) 4DeamidationeNN 1 (N137) 1 (N392) 4NT 0 2 (N58, N211) 4NH 0 2 (N206, N437) 4DG 0 2 (D283, D404) 42 (D167, DS1 (D402) 6D170) IsomerizationeDD 0 0 03 (D74, D91, DT 06 D252) DH 0 0 0Hydrolysisf DP 0 1 (D273) 2CDR Glycation K 0 1 (K66) 2C-terminal Clip K 0 1 (K450) 2N-linked NXS / TZg 0 1 (N300) 2glycosylation a. Amino acid / motif (potential hot spots). b. Number represents number of hotspots per chain. Specific hotspot residue in parenthesis. Hotspot residues in CDRs are bold. c. Total number is for the mature protein. d. All tryptophans are listed, however tryptophans in the CDRs are of primary concern. e. Canonical motif for deamidation and isomerization. In general, deamidation rates have a hierarchy of NG > NS > NN, NT, NH. Asp isomerization has a similar hierarchy, DG > DS> DD, DT, DH. Degradation rates are also affected by protein structure. f. Canonical motif for hydrolysis. g. The consensus N-linked glycosylation site is defined by four residues N-X-S / T-Z. The glycosylation site is essentially fully occupied if both X and Z residues are not proline. If either X or Z residues are proline, there is only trace level glycosylation. Note: HC: N62 may contain trace glycosylation. N300 is not likely to be deamidated due to N-linked glycans occupancy. The abundance of the post translational modifications in a sample of antibodyNI006 / ALXN2220 is shown in Table 5:Table 5. Relative abundance of PTMsPTM Chain Location Domain Relative Abundance (%)Pyro-Glu HC 1 N-Terminus 99.2Lysine Loss HC 450 C-Terminus 95.1Glycation2LC 1 No Site Specific Information HC 4Deamidation3 HC N58 CDR2 <1.0N318 CH2 7.5N387 CH3 2.2Oxidation4 HC M71 CH1 <1.0M115 CH1 1.4M255 CH2 2.7M361 CH3 <1.0M431 CH3 1.1In summary, N-linked glycosylation of the heavy chain, N-terminal pyro-glutamic acid modified from N-terminal glutamine, and C-terminal lysine clipping of the heavy chain are the major post-translational modifications of NI006 / ALXN2220. Moreover, charge variant analysis has been performed and the results are listed in Table 6:Table 6. Charge variantsVariant PTM Chain Location DomainAcidic Deamidation HC N58 CDR2N328 CH2N387 CH3Sialyated N-HC N300 CH2Glycosylation Galactosylated N-HC N300 CH2Glycosylation Truncation HC 58N / T59 CDR2Glycation @ Lysine Distributed evenly across all Lysine inHC and LC Basic Isomerization HC D283 CH2Lysine HC K450 C-TerminusProline Amidation withHC P448 C-TerminusGlycine, Lysine Loss HMWS by Size Exclusion Chromatography Example 3. ALXN2220 manufacturing process In this Example, scale up of ALXN2220 drug substance (DS) manufacturing process, from phase I at 500L scale (Process A1) to phase III at 2000L scale (Process A2) is described, with the major upstream process changes summarized in Table 7. ALXN2220 product quality results at DS release are summarized in Table 7. Notably, the imaged capillary isoelectric focusing (iCIEF) acidic % of 1st2000L DS batch (GMP 1 (A2)) was considerably higher than historical results from process A1 at 500L scale (Figure 1). To mitigate the risk in high acidic species observed from 1st2000L DS batch (GMP 1 (A2)), multiple upstream process parameters were evaluated using small scale bioreactors, among which the most effective parameter to reduce acidic species was identified to be effective pH controlled by pH setpoint and dead band. When 0.05 pH dead band was applied (culture ID: #1), the effective pH (reflected by online pH) was approximately 0.05 and 0.15 lower than that from pH dead band 0.10 (culture ID: #2) and pH dead band 0.20 (culture ID: #3, respectively, in the majority of cell culture production phase (day 5 to 14) (Figure 5). Table 7. ALXN2220 Upstream Production Process Summary Phase I Phase III Production Process A1 Process A2 Bioreactor GMP2, GMP3, GMP4, ParametersGMP1, GMP2, GMP3, GMP4 GMP1GMP5, GMP6, GMP7, GMP8, GMP9 Production Cell Line CHO-K1 derived cell line Production MediaCytiva ActiPro Media BTarget Seeding Density (1060.45 0.50 0.40cells / mL) pH setpoint 7.00 6.90pH dead band 0.20 0.20 0.05Growth Temperature36.5 36.5(°C) Production Temperature31.00 31.00(°C) Temperature shift VCD range (10618-23 15-24 20-26cells / mL) FM1: FM1: 3% (day 3 and 12), 4% (day 5, 7 Nutrition 3% on day 3, 5, 7 and 10 FM2: 0.3% on d and 10) Feeding ay 3, 5, 7, and 10 FM2: 0.3% (day 3 and 12), 0.4% (day 5, 7 and 10) The cell culture samples from all three bioreactors were purified by small-scale protein A,followed by product quality testing (Tables 8 and 9). Small scale data indicated reducing thepH dead band from 0.20 to 0.05 led to considerable reduction on acidic species (Figure 3). Quite surprisingly, reducing pH dead band from 0.20 to 0.05 also led to reduction on Man 5 (Figure4) – more robust control for high mannose species, and no meaningful adverse impact on otherproduct quality attributes tested (Tables 8 and 9).Following the small-scale experiment concluding the effectiveness of pH control strategy on reduction of acidic species and Man 5 (mentioned above), two additional upstream parameters (target seeding density and temperature shift viability cell density range) were further changed to confirm the process robustness before implementation at 2000L scale Process A2 starting from 2nd2000L batch. DS release results from iCIEF (Figure 5) and N-glycan (Figure 2) at 2000L scale confirmed the effectiveness and robustness of iCIEF acidic and Man 5 controlstrategy for ALXN2220. The glycosylation profile has been determined using the above-mentioned released N-Glycan method.Table 8. ALXN2220 Drug Substance Product Quality Summary (Phase 1)Phase IProduct Quality Results Process A1 Drug Substance GMP 1 GMP 2 GMP 3 GMP 4M3+1F 0.2 0.1 0.2 0.2M5 4.5 3.9 4.2 3.2G0-GN 1.7 1.4 1.7 1.5G0F-GN 2.9 2.6 3.7 3.1G0 5.8 6.6 4.6 6.1G0F 49.4 51.0 52.4 52.7N-Glycan (%) G1F-GN 2.2 1.9 2.0 2.0+G1a G1b 0.5 0.5 0.5 0.6G1F 25.7 25.6 23.7 24.5G2F 4.1 4.2 3.5 3.6G2FS1 0.4 0.4 0.3 0.4G2FS2 0.1 0.1 0.1 0.1Main 66.0 62.1 64.7 61.2iCIEF (%)Acidic 28.7 31.6 27.5 32.7Basic 5.3 6.3 7.8 6.1Main 99.2 99.2 99.1 99.1SEC (%)HMW 0.7 0.8 0.8 0.8LMW Not Reported 0 0 0CE-SDS NR (%) Main Peak 98.7 98.6 98.3 98.7Light chain + CE-SDS R (%)97.4 96.9 97.2 97.7heavy chainTable 9. ALXN2220 Drug Substance Product Quality Summary (Phase 2)Phase III Product Quality Process A2 Drug Substance Results GMP1 GMP2 GMP3 GMP4 GMP5 GMP6 GMP7 GMP8 GMP9M3+1F 0.2 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2M5 3.4 1.8 2.4 1.9 1.9 1.8 1.9 1.4 1.7G0-GN 1.4 0.9 1.1 1.1 0.9 0.9 1.2 0.8 0.9G0F-GN 3.2 2.6 3.6 2.6 2.8 2.8 2.5 2.8 2.9G0 4.1 4.7 3.0 5.0 4.8 4.9 5.0 4.1 4.3N-G0F 48.9 55.2 59.3 57.1 56.7 58.0 54.7 59.2 56.3Glycan G1F-GN (%) +G1a2.6 1.8 1.4 1.6 1.6 1.5 1.8 1.4 1.6G1b 0.5 0.5 0.2 0.4 0.5 0.5 0.4 0.4 0.4G1F 28.7 26.4 23.3 24.8 24.4 23.3 25.7 23.5 24.8G2F 4.2 3.8 3.3 3.6 3.5 3.3 3.9 3.4 3.8G2FS1 0.5 0.5 0.4 0.4 0.4 0.3 0.5 0.4 0.4G2FS2 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.2Main 58.3 66.1 63.8 65.8 69.4 69.6 67.7 65.3 64.9iCIEF (%)Acidic 38.3 30.0 31.3 30.3 27.0 26.4 27.7 30.3 30.5Basic 3.3 4.0 4.8 3.9 3.6 3.9 4.7 4.4 4.5Main 99.1 99.1 99.2 99.2 99.1 99.2 99.2 99.3 99.3SEC (%)HMW 0.9 0.9 0.8 0.7 0.9 0.8 0.8 0.7 0.7LMW 0 0 0 0 0 0 0 0 0CE- SDS Main97.9 98.4 98.4 98.5 98.4 98.5 98.5 98.5 98.4NR (%) Peak CE- Light SDS R chain +97.1 97.6 97.6 97.7 97.7 97.7 97.6 97.6 97.6(%) heavy chainTable 10. Small Scale Study Product Quality Result SummaryCulture ID and pH Condition Product Quality Results#1 #2 #36.90 ± 0.05 6.90 ± 0.10 6.90 ± 0.20M5 1.6 1.9 3.1G0-GN 0.7 0.8 1.2G0F-GN 2.6 2.6 3.1N-Glycan (%)G0 4.1 4.1 4.5G0F 61.8 59.5 53.0G1F 21.9 23.4 26.0G2F 3.2 3.3 3.8Main 60.1 59.9 57.0iCIEF (%)Acidic 32.8 32.1 36.2Basic 7.1 8.0 6.8Main 97.7 97.8 98.3SEC (%)HMW 2.3 2.2 1.7LMW ND ND NDCE-SDS NR (%) Main Peak 97.7 97.7 97.8In summary, reducing pH dead band from 0.20 to 0.05 surprisingly led to reduction on Man 5,which cannot only be seen in Figure 4, but also in Table 9, which clearly shows that batch GMP1 (A2) (pH dead band: 0.2) has a significantly higher Man5 content than all other batches GMP2(A2) to GMP9 (A2) (pH dead band: 0.05).Example 4. Stability Studies of the anti-TTR monoclonal antibody formulationFormulation development of NI006 / ALXN2220 included studies designed to select a buffer system and excipients to stabilize the protein. The formulation was developed to prevent product loss, as well as minimize the purity and bioactivity decline against stresses encountered during production, storage, shipping, and handling. A pH buffer screening study was performed to determine the optimal buffer system for drug product formulation.20 mM histidine buffer, at pH 5.8 was chosen as the final buffer system. Different types of excipients, including disaccharides (such as sucrose and trehalose), aminoacids (such as L-arginine HCl), polyhydric alcohols (such as sorbitol), and surfactants (such aspolysorbate 80) were evaluated though excipient studies. Samples were incubated at 40ºC for up to 4 weeks. The thermal stability, formation of insoluble aggregates, and purity weremonitored. Sucrose and polysorbate 80 were chosen as the optimal excipients forNI006 / ALXN2220 formulation, as they were shown to minimize the decrease of SEC, cIEF and caliper purity, thus retaining product purity.In an excipient concentration screening study, finally three different polysorbate 80concentrations (0.02%, 0.04% and 0.06% (w / v)), and two sucrose concentrations (6.5% and 8%(w / v)) were tested. Three stress conditions were used in the screening: agitation, thermal and freeze-thaw. In agitation study, the samples were placed at 25 °C, with or without agitation at 200 rpm for up to 7 days. In thermal study, the samples were placed at 40 °C for up to 2 weeks. And in freeze-thaw study, the samples were frozen and thawed for up to 5 cycles. Appearance, pH, protein concentration, number of sub-visible particles, and purity were evaluated. A polysorbate 80 concentration of 0.03% (w / v) was chosen as the surfactant strength, since subvisible particle formation was effectively suppressed and high SEC purity was maintained. A comparison study was conducted to compare two formulations with 6.5% or 8% (w / v) sucrose concentration. No substantial differences, between formulations of 6.5% and 8% (w / v) sucrose, were observed in DSC (Differential Scanning Calorimeter), appearance, pH, protein concentration, SEC, cIEF, CE-SDS (non-reduced & reduced), sub-visible particles, and potency after incubation at 40ºC for 1 month or incubation at 25 °C for 3 months. The final formulation developed is NI006 / ALXN2220 at a target concentration of 50 mg / mL in 20 mM histidine buffer, 8% (w / v) sucrose, 0.03% (w / v) polysorbate 80, and a pH of 5.8. The excipients were selected according to their stabilizing effect on the drug product. L-Histidine and L-Histidine monohydrochloride, at a concentration of 20 mM, stabilize the pH in the liquid state. Sucrose, at a concentration of 8% (w / v), modifies the osmolality to be isotonic, stabilizes the NI006 / ALXN2220 protein against aggregate formation in the liquid state, and serves as a cryo-protectant during freeze / thaw. Polysorbate 80, at a concentration of 0.03% (w / v), was chosen to stabilize NI006 / ALXN2220 protein against surface-induced protein denaturation or aggregation in the liquid state. Manufacturing Process Development The drug product manufacturing process consists of drug substance thawing, pooling andmixing, sterile filtration, aseptic filling, stoppering, capping, visual inspection, and bulkpackaging. Sterile filtration was chosen as the method to obtain the sterile drug product and is performed by using two series connected sterile filters (0.22 µm, PVDF). Prior to and after sterile filtration, water bubble point testing for the filters is performed to assure filter integrity. The compatibility of the drug product with the contacting components on the filling line, the impact of shear stress caused by the peristaltic pump, and stability under light exposure have been evaluated to mitigate potential adverse impact on product quality attributes during manufacturing. A non-clinical lot (lot 201901004) and three clinical lots (lot 201903038, lot 201904050 and 20200801) have been filled. The non-clinical lot and clinical lots used the same fill volume, container closure system, sequence of unit operations, and storage conditions. No significant changes were made to the drug product manufacturing process between the non-clinical lot and clinical lots. Minor differences are described below:• A 2 L scale was used for the non-clinical lot and 14 L scale was used for the clinicallots.• The formulation used for the non-clinical lot 201901004 was 50 mg / mL in 20 mMhistidine buffer, 8% sucrose (w / v), and 0.03% polysorbate 80 (w / v), pH 5.8. The formulation used for clinical lots 201903038 and 201904050 was 50 mg / mL in 20mM histidine buffer, 6.5% sucrose (w / v), and 0.03% polysorbate 80 (w / v), pH 5.8. The formulation used for the clinical lots 20200801 was 50 mg / mL in 20mM histidine buffer, 8% sucrose (w / v), and 0.03% polysorbate 80 (w / v), pH 5.8.• A 5 L glass bottle was used for pooling and mixing of the drug substance for the non-clinical lot, and a 50 L mixing bag was used for pooling and mixing of the drug substance for the clinical lots. Bulk Drug Substance Thawing, Pooling and MixingFrozen drug substance stored in 2 L PETG bottles is thawed at room temperature (18 - 24 °C)in a room protected from light. After complete thawing, the drug substance is pooled into a 50 L mixing bag and stirred at an appropriate speed so that movement is observed withoutgenerating foam. The mixing time is controlled at 15 - 20 minutes. Prior to sterile filtration,samples are taken for pH, protein concentration, osmolality, and bioburden. Sterile Filtration The bulk drug substance is aseptically filtered in a Grade A environment via a peristaltic pump through two series connected 0.22 ^m sterile filters into a sterile 20 L single use bag. Prior to and after sterile filtration, filter integrity testing is performed on both filters. Aseptic Filling Aseptic filling is performed inside the RABS unit, which fully encloses the filler and provides a Grade A environment. The RABS unit separates the operator from the aseptic interior. All filling components are autoclaved and aseptically assembled. Sterile, depyrogenated 2 mL (2R) glass vials are filled to a target volume of 2.25 mL. Fill weight checks are performedperiodically during the filling process to ensure the fill weight is 2.233 - 2.442 g / vial.Stoppering Filled vials are automatically stoppered with 13 mm rubber stoppers inside the RABS unit. The stoppers are steam sterilized at 122 °C for 30 minutes. Capping The stoppered vials are transferred to the capping machine via conveyor belt under Grade A laminar flow protection. The stoppered vials are capped with 13 mm plastic aluminum flip-off caps. The caps are steam sterilized at 122 °C for 30 minutes. Visual Inspection A manual 100% visual inspection is performed on the capped vials by production personnel, followed by a statistically based AQL (acceptable quality limit) inspection by Quality Assurance. Release and stability samples are taken after visual inspection. Bulk Packaging and Storage The filled drug product vials are then bulk packaged and labelled. Bulk packaged drug productvials are stored at 2 - 8 °C.Container Closure System The container closure system for the drug product is a 2 mL (2R) Type I glass vial sealed with a 13 mm rubber stopper and a 13 mm flip-off aluminum cap. The components were selected for their durability to sterilization and depyrogenation processes, as well as non-reactive contact surfaces that are optimally compatible with proteins. The compatibility of the container closure system with the drug product is evaluated by the accelerated and long-term stability studies presented below. The integrity of the container closure system was demonstrated by the dye ingression test. Drug product vials were immersed under colored dye and held under vacuum before depressurized and the infiltration of the dye into the vials examined. The container and closure system achieved 100% air tightness. Container closure integrity testing (CCIT) is performed annually in the stability program using a non-destructive vacuum decay method. The product contact materials, the glass vial and rubber stopper, have been tested per USP and Ph.Eur. requirements and are suitable for parenteral use. Compliance is verified on the Certificate of Conformance provided by the vendor with each lot of vials and stoppers. Analytical procedures Color Color complies with Ph. Eur. 2.2.2. Chromatic aberration method is used for color measurement. Clarity Clarity complies with Ph. Eur.2.2.1. Light scattering method is used for clarity measurement. pH Complies with USP <791> and Ph. Eur.2.2.3. Potentiometric determination method is used for pH measurement. Osmolality Complies with USP <785> and Ph. Eur.2.2.35. The osmolality is determined indirectly by the measurement of the depression of freezing point of the solution. iCIEF Whole column Imaging Capillary Isoelectric Focusing (iCIEF) is an identity and purity analysis method used to separate proteins according to isoelectric points (pI) and to monitor the percentage of charge variant species in a protein sample. pI is an intrinsic property of a specific protein molecule and is the pH at which the protein molecule does not carry any net electrical charge. Under an external electric field, charge variants move along a continuous pH gradient formed by ampholytes and stop where the pH equals its pI. At that pI, the protein carries no net electrical charge and is not drawn by either of the electrodes. Therefore, different monoclonal antibody species with different pI values are separated and focused at different positions. The pI values and relative abundance of the resolved peaks can be identified and quantified using chromatographic software. To meet the acceptance criteria of “conforms to profile of the reference standard”, the electropherogram should show comparable peak profile to the electropherogram of the reference standard. In addition, the difference of pI values of the main peak between tested sample and the reference standard (average) should be no more than 0.2. SEC-HPLC Size Exclusion Chromatography-High Performance Liquid Chromatography (SEC-HPLC) is a purity analysis method that separates proteins based on their sizes. The stationary phase is composed of inert particles packed into a dense three-dimensional matrix. The particles have small pores which only allow species below a certain size to enter. Larger molecules simply pass by the pores as they are too large to enter the pores. Larger molecules therefore flow through the column quicker than smaller molecules; the smaller the molecule, the longer the retention time. Following separation, the relative percentages of High Molecular Weight (HMW) species, monomer, and Low Molecular Weight (LMW) species are quantified via UV detection. CE-SDS (Reduced) Reduced Capillary Electrophoresis-Sodium Dodecyl Sulfate (CE-SDS) is a purity analysis method that separates proteins based on their electrophoretic mobility, where smaller size proteins move faster than larger size proteins. In this method, the test samples are denatured by heating in the presence of SDS. The samples are reduced by the addition of reducing agent beta- mercaptoethanol (BME) to the sample solution. Separation is performed though an uncoated capillary and the protein samples are detected with a photo diode array (PDA) detector at 220 nm. Results are reported as percent purity. CE-SDS (Non-reduced) CE-SDS (Non-reduced) is a purity analysis method that separates proteins based on their electrophoretic mobility, where smaller size proteins move faster than larger size proteins. In this method, the test samples are denatured by heating in the presence of SDS. The alkylating reagent N-Ethylmaleimide (NEM) is added to the sample solution in order to prevent the sulfhydryls from binding to other sulfhydryls. Separation is performed through an uncoated capillary and the protein samples are detected with a PDA detector at 220 nm. Results are reported as percent purity. Bioburden Bioburden testing is performed by membrane filtration based on USP <61> and Ph. Eur.2.6.12. 10 mL of drug substance sample is filtered through the sterile surface of a 0.45 μm membrane. The filter membrane is then transferred onto a culture plate of Soybean-Casein Digest Agar for determination of total aerobic microbial count (TAMC). Another filter membrane used for 10 mL drug substance sample filtration is transferred onto a culture plate of Sabouraud Dextrose Agar for determination of total combined yeasts and molds count (TYMC). Endotoxin Bacterial endotoxin testing is performed by kinetic turbidimetric assay and is established based on USP <85> and Ph. Eur. 2.6.14. The endotoxin generated by gram-negative bacteria is detected using amebocyte lysate from the horseshoe crab, which coagulates with endotoxin. By establishing the correlation between endotoxin concentration and the time needed to reach a predetermined absorbance of the reaction mixture, or the rate of turbidity development, the endotoxin concentration can be calculated. ELISA (Binding Assay) An ELISA method is used to assess the binding potency of the NI006 / ALXN2220 antibody. Samples, control, and reference standard at appropriate dilutions are loaded onto misfolded- TTR (antigen for NI006 / ALXN2220) coated half-area 96 well plate(s). After washing plate, horseradish peroxidase (HRP)-conjugated goat anti-human IgG is added to the wells, allowing interaction with bound NI006 / ALXN2220 antibody captured by misfolded-TTR. After a final wash step, TMB substrate solution is loaded into the wells. TMB specifically reacts with peroxide in the presence of peroxidase and produces a colorimetric signal that is proportional to the amount of NI006 / ALXN2220 protein bound to the wells. The color development is stopped and optical density is measured at 450 nm (minus 560 nm for wavelength correction). Sample and reference standard dose response curves are plotted according to a 4 parameter logistic (auto-estimate) regression model using SoftMax Pro GxP software. Individual EC50 values are calculated for samples and reference standards. Relative binding activity of the sample is calculated using the following formula: Relative binding activity of the sample (%) = (EC50 of the reference standard / EC50 of the sample) × 100% Protein Concentration Protein in solution absorbs ultraviolet light at a wavelength of 280 nm, due to the presence of aromatic amino acids in the protein molecule. According to Beer-Lambert law, the absorbance (A) of a protein solution at a fixed wavelength is related to the protein concentration (C), the cell path length (l), and the extinction coefficient (ε) of the protein as follows: A = C l ε. Unlike traditional UV-Vis methods that rely on a single absolute absorbance value, the slope spectroscopy method uses section data (absorbance vs. path length) to determine a slope valuefor quantitation of sample concentration using the slope spectroscopy equation (Slope = ε C)which is derived from the Beer-Lambert law. Cell-based Assay THP-1 is a human monocytic cell line. NI006 / ALXN2220 is an antibody against misfolded TTR. The bioactivity of NI006 / ALXN2220 is to stimulate THP-1 cell to produce IL-8 bybinding the mis-TTR in cell culture. Briefly, approximately 2 × 104 cells per well of THP-1cells in assay medium are seeded into a 96-well cell culture plate at 100 μL / well, then a mixtureof serial dilutions of NI006 / ALXN2220 mAb standard (final concentration: 2000 - 0.039 g / mL)and misfolded-TTR (final concentration: 10 μg / mL) are loaded into duplicate wells at 100μL / well. After 20 - 24 hours of incubation at 37 °C with 5 % CO2, IL-8 production is measuredusing human IL-8 ELISA kit. Compatibility studies The compatibility of NI006 / ALXN2220 with the clinical in-use materials was evaluated. The compatibilities with the following clinical administration settings were assessed: ^Bag and infusion line under PVC setting - the IV bag, IV line, and filter are composedof PVC material^ Bag and infusion line under non-PVC setting - the IV bag, IV line, and filter arecomposed of non-PVC material^ Syringe under PVC setting - the perfusor line and filter are composed of PVC material^ Syringe under non-PVC setting - the perfusor line and filter are composed of non-PVCmaterialThree concentrations (1.0 mg / mL, 20.0 mg / mL, and 50.0 mg / mL) at 2 - 8 °C for 24 hoursfollowed by 25 °C for 6 hours (30 hours in total) were tested. Saline and glucose were used as the diluents for the concentration of 1.0 mg / mL and 20.0 mg / mL. Results are shown in Tables11 and 12. Table 11. Results of In-use Compatibility Studies. Dose Diluent Contact Material Appearance Protein concentration(mg / ml) T0 T-30 hr T0 T-30 hrSaline Bag and infusionCl, SO, many Cl, SO, many1.0 1.0line under PVC white dots white dots setting Bag and infusion Cl, SO, many Cl, SO, many1.0 1.0line under non- white dots white dots PVC setting Syringe under Cl, SO, many Cl, SO, many0.9 1.0PVC setting white dots white dots Syringe under Cl, SO, many Cl, SO, many0.9 1.0Low dose non-PVC setting white dots white dots (1.0 mg / ml)Glucose Bag and infusion Cl, C, FoP Cl, C, FoP 1.0 1.0line under PVC setting Bag and infusionCl, C, FoP Cl, C, FoP 1.0 1.0line under non- PVC setting Syringe underCl, C, FoP Cl, C, FoP 1.0 0.9PVC setting Syringe underCl, C, FoP Cl, C, FoP 1.0 0.9non-PVC setting Saline Syringe under Cl, SO, FoP SY, SO, 19.9 19.7PVC setting many white dots Syringe underCl, SO, FoP SY, SO, 19.8 19.5non-PVC setting many white Mid dose dots (20 mg / ml)Glucose Syringe under Cl, C, FoP Cl, C, FoP 19.9 19.6PVC setting Syringe underCl, C, FoP Cl, C, 1 19.7 19.8non-PVC setting particle NA Bag and infusion SY, SO, FoP SY, SO, FoP 49.0 48.7line under PVC settingDose Diluent Contact Material Appearance Protein concentration(mg / ml) T0 T-30 hr T0 T-30 hrHigh doseNA Bag and infusion SY, SO, FoP SY, SO, FoP 49.5 48.9(50 mg / ml) line under non- PVC setting Cl: colorless; SY: slightly yellow; C: clear; FoP: free of visible particles; SO: slightly opalescent1The concentration is the same as the NI006 / ALXN2220 drug product concentration. Table 12. Results of In-use Compatibility Studies (Continued) Dose Diluent Contact SEC-HPLC Sub-visible ParticlesELISA (Binding Material (10 µm / 25µm) Assay) T0 T-30 hr T0 T-30 hr T0 T-30 hrSaline Bag and 97.8 98.4 164 / 6 14 / 0 94% 96%infusion line under PVC setting Bag and97.8 98.6 50 / 1 19 / 1 93% 76%infusion line under non- PVC setting Syringe97.3 99.1 57 / 1 136 / 5 86% 81%Low dose under PVC (1.0 setting mg / ml) Syringe97.1 98.9 29 / 0 7 / 0 124% 89%under non- PVC setting Glucose Bag and 99.4 99.4 5 / 0 3 / 0 112% 100%infusion line under PVC setting Bag and99.4 99.4 8 / 0 1 / 0 91% 118%infusion line under non- PVC settingDose Diluent Contact SEC-HPLC Sub-visible ParticlesELISA (Binding Material (10 µm / 25µm) Assay) T0 T-30 hr T0 T-30 hr T0 T-30 hrSyringe99.4 99.4 6 / 0 6 / 0 127% 103%under PVC setting Syringe99.3 99.4 5 / 0 1 / 0 103% 98%under non- PVC setting Saline Syringe 99.3 99.3 1 / 1 41 / 1 84% 100%under PVC setting Syringe99.3 99.3 7 / 1 38 / 1 98% 82%under non- Mid dose PVC setting (20Glucose Syringe 99.3 99.4 9 / 0 5 / 1 72% 94%mg / ml) under PVC setting Syringe99.3 99.4 4 / 0 13 / 1 59%2 72%under non- PVC setting NA1Bag and99.3 99.4 16 / 0 4 / 0 86% 110%infusion line High under PVC dose (50 setting mg / ml) NA1Bag and99.3 99.4 13 / 1 4 / 0 98% 98%infusion line under non- PVC setting1The concentration is the same as the NI006 / ALXN2220 drug product concentration.2The variability of the result is due to assay variability. All results from the in-use compatibility study are within the acceptance criteria. The result is not considered safety relevant considering that, within the short in-use timeframe, the most probable incompatibility with plastics materials would be adsorption (addressed by protein concentration) and visible particle formation (addressed by the compendial method). In the saline group, visible particles were observed, indicating that NI006 / ALXN2220 is less stable in saline. The data show that when using glucose as the diluent, no substantial changes in the appearance, protein concentration, sub-visible particle, SEC-HPLC, and ELISA binding assay were observed. NI006 / ALXN2220 at concentrations of 1.0 mg / mL, 20.0 mg / mL, and50.0 mg / mL is stable at 2 - 8 °C for 24 hours followed by 25 °C for 6 hours (30 hours in total).NI006 / ALXN2220 is compatible with the clinical in-use materials evaluated. A concentration at 0.15 mg / mL, 10-fold lower than the lowest dose concentration in the clinical trial, was also investigated. Variations were observed in the protein concentration and ELISA testing. The variation in the ELISA testing may be caused by the protein concentration variation, which may be caused by protein adsorption to the contacting materials. In conclusion it was decided to use 5% glucose as diluent for clinical in-use. In the following Table 13, batch analysis data are listed exemplarily for non-clinical lot 201901004 and clinical lot 201903038. Table 13. Batch Analyses Test Acceptance Criteria 201901004 201903038Color Not more colored than B7 B7B4 Clarity ≤ 18 NTU 5.3 NTU 5.9 NTUVisible Particles Liquid, essentially freeNo visible particles Liquid, essentially free of of visible particles present visible particles Extractable≥ 2.0 mL ≥ 2.0 mL ≥ 2.0 mLVolume Sub-visible ≥10 μm: ≤ 6000 ≥ 25 μm: 0 ≥10 μm: 9 Particles particles / container particles / container; particles / container ≥25 μm: ≤ 600 ≥ 10 μm: 2 ≥25 μm: 0 particles / container particles / container; particles / container ≥ 5 μm: 44 particles / container; ≥ 2 μm: 346 particles / container pH 5.8 ^ 0.5 5.8 5.8Osmolarity ≥240 mOsmol / Kg 312 mOsmol / kg 264 mOsmol / kgiCIEF Conforms to profile ofpI: 9.3; Conforms to profile of the reference standard Main peak: 63.9%; the reference standardTest Acceptance Criteria 201901004 201903038Main peak ≥ 50.0% Acidic peaks: 28.6%; Main Peak: 64.7% Acidic peaks ≤ 40.0% Basic peaks: 7.5% Acidic peaks: 29.4% Basic peaks ≤ 15.0% Basic peaks: 6.0% SEC-HPLC Main peak (monomer) ≥Monomer: 99.1%; Monomer: 99.3%; 95.0%; HMWS: 0.8%; HMWS: 0.6% HMWS% ≤ 5.0% LMWS: 0.0% LMWS: 0.0% Report LMWS% CE-SDS Light chain + heavy Purity (LC+HC): 97.8% Purity (LC+HC): 96.9%2 (reduced) chain: ≥ 90.0% Light chain: 29.2%; Heavy chain: 68.6%; Minor species: 2.2%; CE-SDS (non-Main peak ≥ 90.0% Total pre-peaks: 1.4%;Main Peak: 97.8% reduced) Total aggregates: 0.4%; Purity: 98.2% Sterility No growth No growth No growthCCIT Pass Pass NAEndotoxin < 4.0 EU / mL < 0.40 EU / mL < 0.40 EU / mLELISA (Binding100 ^ 50% of reference 96% relative potency 98% of referenceAssay) standard standard Protein50.0 ^ 5.0 mg / mL 49.9 mg / mL 49.2 mg / mLConcentration Polysorbate 80 0.030 ^ 0.015% 0.031% 0.029%Cell-basedReport Result 129% 117%Assay (Exploratory Specification)1Acceptance criteria are not set for the non-clinical lot; data are reported for information only.2This result is the average of 6 injections from a retest. The original result is 92.2% for (LC+HC). A root cause for the original result was not identified. As reference standard, a composition comprising 50 mg / mL of the antibody formulated in 20 mM histidine buffer, 8% (w / v) sucrose, and 0.03 % (w / v) PS80 at pH 5.8 and stored at -70 ± 10 °C in vials that were filled with 100 µl was used. Additional testing was performed to qualify the reference standard and the results are shown in Table 14. Table 14. Qualification results for reference standard Test Results Protein Concentration 50.7 mg / mL ELISA (Binding Assay) 93 % relative potency iCIEF pI:9.3; Main peak: 64.2%; Acidic peaks: 28.3%; Basic peaks: 7.5% SEC-HPLC Monomer: 99.2%; HMWS:0.8%; LMWS: ND CE-SDS (Reduced) Light chain: 30.5%; Heavy chain: 66.8%; Minor species: 2.7%; Purity (LC+HC): 97.3% CE-SDS (Non-reduced) Total pre-peaks: 1.5%; Total aggregates: 0.2%; Purity: 98.3% Calibration of protein concentration and potency was conducted for the reference standard. The potency of the reference standard is assigned a value of 100% relative potency. Stability Studies Non-clinical lot 201901004 and clinical lot 201903038 were placed on stability testing. The non-clinical lot (201901004) has 1 month of stress stability data, 6 months of accelerated stability data, and 18 months of long-term stability data. The clinical lot (201903038) has 1 month of stress stability data and 6 months of accelerated stability data, and 12 months of long- term stability data. Under stress conditions, both clinical lot (201903038) and nonclinical lot (201901004) show trend of significant decrease in iCIEF main peak (%) and increase in acidic peaks (%), while no significant changes were observed in other purity assays as well as ELISA binding assay.The shelf life for the drug product is currently set at 24 months stored at 5 ^ 3 ^C, protectedfrom light. The available in-use stability and compatibility data, presented above, indicate that the ready-to-use solution for infusion is stable for up to 24 hours at 2-8°C followed by 6 hours at 25°C after dilution with 5% glucose solution. From a microbiological perspective, the solution for infusion should be used immediately. If not used immediately, the in-use shelf lifeis set to 4 hours at room temperature or 24 hours at 2 - 8 °C. Tables 15 to 18 summarize theavailable stress data for the non-clinical lot 201901004 and clinical lot 201903038. Table 15. Stress Stability Data for Non-Clinical Lot 201901004 at 40 ± 2 °C / 75 ± 5% RH Test T0 1 Week 2 Weeks 1 MonthColor B7 B7 B7 B6Clarity 5.3 NTU 5.4 NTU 6.1 NTU 6.2 NTUVisible Particle No visible particlesNo visible particles No visible particles No visible particles present present present present ≥25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 1particles / container; particles / container; particles / container; particles / container;≥ 10 µm: 2 ≥ 10 µm: 4 ≥ 10 µm: 1 ≥ 10 µm: 4particles / container; particles / container; particles / container; particles / container; Sub-visible Particles ≥ 5 µm: 44 ≥ 5 µm: 37 ≥ 5 µm: 26 ≥ 5 µm: 48 particles / container; particles / container; particles / container; particles / container;≥ 2 µm: 346 ≥ 2 µm: 354 ≥ 2 µm: 388 ≥ 2 µm: 383particles / container particles / container particles / container particles / containerpH 5.8 5.8 5.9 5.9pI: 9.3; pI: 9.3; pI: 9.3; pI: 9.3; iCIEF Main peak: 63.9%; Main peak: 57.5%; Main peak: 53.3%; Main peak: 44.4%; Acidic peaks: Acidic peaks: 34.7%; Acidic peaks: 39.7%; Acidic peaks: 28.6%; Basic peaks: 7.8% Basic peaks: 7.0% 49.8%; Basic peaks: 7.5% Basic peaks: 5.8% Monomer: 99.1%; Monomer: 99.0%; Monomer: 97.5%; Monomer: 96.0%; SEC-HPLC HMWS: 0.8%; HMWS: 0.9%; HMWS: 1.0%; HMWS: 1.2%; LMWS: 0.0% LMWS: 0.2% LMWS: 1.4% LMWS: 2.8% Light chain: 29.2%;Light chain: 29.2%; Light chain: 29.4%; Light chain: 29.4%;CE-SDS Heavy chain:Heavy chain: 68.3%; Heavy chain: 67.5%;Heavy chain: (Reduced) 68.6%; Minor species: 2.4%; Minor species: 3.1%; 65.9%; Minor species: 2.2 Purity: 97.6% Purity: 96.9 % Minor species: CE-SDS Total pre-peaks: Total pre-peaks: Total pre-peaks: Total pre-peaks:1.4%; 2.0%; 2.7%; 4.1%;(Non- Total aggregates: Total aggregates: Total aggregates: Total aggregates:reduced) 0.4%; 0.2%; 0.3%; 0.5%;Purity: 98.2% Purity: 97.8% Purity: 97.0% Purity: 95.4% ELISA 96% relative108% relative potency 74% relative potency 112% relative(Binding potency potency ProAtesinsaCy)onc. 49.9 mg / mL 49.7 mg / mL 50.2 mg / mL 50.0 mg / mLTable 16. Stress Stability Data for Exploratory Specification for Non-Clinical Lot 201901004 at 40 ± 2 °C / 75 ± 5% RH Test T0 1 Week 2 Weeks 1 MonthCell-based129% 121% 105% 148%Assay Table 17. Stress Stability Data for Clinical Lot 201903038 at 40 ± 2 °C / 75 ± 5% RH Test Acceptance T0 1 Week 2 Weeks 1 MonthColor NotCmroirteecroialored B7 B7 B7 B6than B4 Clarity ≤ 18 NTU 5.9 NTU 6.1 NTU 6.7 NTU 6.5 NTULiquid, essentially Liquid, Liquid, Liquid, Liquid, Visible free of visible essentially free essentially free essentially free essentially free Particle particles of visible of visible of visible of visible Sub-visible ≥ 10 µm: ≥ 10 µm: 9 ≥ 10 µm: 6 ≥ 10 µm: 12 ≥ 10 µm: 8 particle ≤ 6000 particles / vial particles / vial particles / vial particles / vial particles / vial ≥ 25 µm: 0 ≥ 25 µm: 2 ≥ 25 µm: 1 ≥ 25 µm: 0 ≥ 25 µm: ≤ 600 particles / vial particles / vial particles / vial particles / vial particles / vial pH 5.8 ^^0.5 5.8 5.8 5.8 5.8Main peak% ≥ Main Peak%: Main peak%: Main peak%: Main peak%: 50.0% 64.7% 59.6% 54.2% 42.5% iCIEF Acidic peaks% ≤ Acidic peaks%: Acidic peaks%: Acidic peaks%: Acidic peaks%: 40.0% 29.4% 35.1% 40.5% Basic 52.9% Basic peaks% ≤ Basic peaks%: Basic peaks%: peaks%: 5.3% Basic peaks%: 15.0% 6.0% 5.3% 5.3% Main peak Monomer: Monomer: Monomer: Monomer: (monomer) ≥ 99.3% 99.2% 99.0% 97.2% SEC-HPLC 95.0% HMWS: 0.6% HMWS: 0.7% HMWS: 0.7% HMWS: 0.8% HMWS% ≤ 5.0% LMWS: 0.0% LMWS: 0.1% LMWS: 0.3% LMWS: 2.1% Report LMWS% CE-SDS Light chain + Light chain + Light chain + Light chain + Light chain + (Reduced) heavy chain: ≥ heavy chain heavy chain: heavy chain: heavy chain: 90.0% 96.9% 96.5% 95.8% 95.3% CE-SDS Main peak ≥ Main peak: Main peak: Main peak: Main peak: (Non- 90.0% 97.8% 98.1% 97.4% 95.8% reduced) ELISA 88% of 100 ^^50% of 98% of reference 84% of reference 76% of reference (Binding reference reference standard standard standard standard Assay) standard Protein50.0 ^^5.0 mg / mL 49.2 mg / mL 49.5 mg / ml 49.3 mg / ml 48.9 mg / mlConcentration Table 18. Stress Stability Data for Exploratory Specification for Clinical Lot 201903038 at 40 ± 2 °C / 75 ± 5% RH Test T0 1 Week 2 Weeks 1 MonthCell-based117% 136% 111% 81%AssayTables 19 to 22 summarize the available accelerated data for the non-clinical lot 201901004and clinical lot 201903038. Table 19. Accelerated Stability Data for Non-Clinical Lot 201901004 at 25 ± 2 °C / 60 ± 5% RH Test T0 1 Month 3 Months 6 MonthsColor B7 B7 B7 B7Clarity 5.3 NTU 6.1 NTU 5.5 NTU 6.0 NTUVisible No visible particles No visible particles No visible particles No visible particles particle present present present presentTest T0 1 Month 3 Months 6 Months10 µm: 2 10 µm: 0 10 µm: 5 ≥ 10 µm: 4 particles / container; particles / container; particles / container; particles / container; ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 0 particles / container; particles / container; particles / container; particles / container; ≥ 5 µm: 44 ≥ 5 µm: 39 ≥ 5 µm: 25 ≥ 5 µm: 95 particles / container; particles / container; particles / container; particles / container; ≥ 2 µm: 346 ≥ 2 µm: 390 ≥ 2 µm: 312 ≥ 2 µm: 646 particles / container particles / container particles / container particles / container pH 5.8 5.9 5.8 5.8pI: 9.3; pI: 9.3; pI: 9.3; pI: 9.3; iCIEF Main peak: 63.9%; Main peak: 62.2%; Main peak: 54.2%; Main peak: 49.1%; Acidic peaks: 28.6%; Acidic peaks: 30.3%; Acidic peaks: 38.3%; Acidic peaks: Basic peaks: 7.5% Basic Basic 44.3%; Basic peaks: 7.5% peaks: 7.5% peaks: 6.6% Monomer: 99.1%; Monomer: 99.1%; Monomer: 98.7%; Monomer: 96.9%; SEC-HPLC HMWS:0.8%; HMWS:0.8%; HMWS:1.0%; HMWS:1.3%; LMWS: 0.0% LMWS: 0.1% LMWS: 0.3% LMWS: 1.8% Light chain: 29.2%; Light chain: 29.2%; Light chain: 30.6%; Light chain: 30.1%; Heavy chain: 68.6%; Heavy chain: 68.4%; Heavy chain: 65.8%; Heavy chain: CE-SDS Minor species: 2.2%; Minor species: 2.4%; Minor species: 3.6%; 64.5%; (Reduced) Purity: 97.8%Purity: 97.6% Purity: 96.4%Minor species: 5.3%; Purity: 94.7%SDS Total pre-peaks: Total pre-peaks: Total pre-peaks: Total pre-peaks:1.4%; 1.6%; 2.6%; 3.6%;(Non- Total aggregates: Total aggregates: Total aggregates: Total aggregates:reduced) 0.4%; 0.3%; 0.3%; 0.4%;Purity: 98.2% Purity: 98.1% Purity: 97.1% Purity: 96.0%ELISA96% relative potency 94% relative potency 134% relative96% relative (Binding potency potency Protein49.9 mg / mL 50.1 mg / mL 50.3 mg / mL 51.0 mg / mLConcentration Table 20. Accelerated Stability Data for Exploratory Specification for Non-Clinical Lot 201901004 at 25 ± 2 °C / 60 ± 5% RH Test T0 1 Month 3 Months 6 MonthsCell-based Assay 129% 117% 140% 94% Table 21. Accelerated Stability Data for Clinical Lot 201903038 at 25 ± 2 °C / 60 ± 5% RH Acceptance TestT0 1 Month 3 Months 6 MonthsCriteria Report result (refer ColorB7 B7 B7 B7to Ph. Eur.) Clarity Report result 5.9 NTU 6.7 NTU 6.5 NTU 6.3 NTULiquid, essentially Liquid, Liquid, Liquid, Liquid, Visible free of visible essentially free essentially free essentially free essentially free Particle particles of visible of visible of visible of visible Sub-visible ≥ 10 µm: ≤ 6000 ≥p1a0rtµicmle:s9 ≥p1a0rtµicmle:s7 ≥p1a0rtµicmle:s1 ≥p1a0rtµicmle:s21Particlesparticles / vial particles / vial particles / vial particles / vial particles / vial≥ 25 µm: ≤ 600 ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 3particles / vial particles / vial particles / vial particles / vial particles / vialpH 5.8 ^^0.5 5.8 5.8 5.8 5.8Main peak% ≥ Main peak%: Main peak%: Main peak%: Main peak%:50.0% 64.7% 61.1% 54.6% 47.8%Acidic peaks% ≤ Acidic peaks%: Acidic peaks%: Acidic peaks%: Acidic peaks%: iCIEF 40.0% 29.4% 33.4% 40.1% 46.8% Basic peaks% ≤ Basic peaks%: Basic peaks%: Basic peaks%: Basic peaks%:15.0% 6.0% 5.5% 5.2% 5.4%Monomer: Main peak Monomer: Monomer: Monomer: 99.3% (monomer) ≥ 95.0% 99.3% 98.9% 97.5% SEC-HPLC HMWS: 0.6% HMWS% ≤ 5.0% HMWS: 0.6% HMWS: 0.8% HMWS: 0.9% Report Report LMWS% Report LMWS% LMWS: 0.3% LMWS: 1.7% LMWS% Light chain + Light chain + Light chain + Light chain + CE-SDS Light chain + heavy heavy chain: heavy heavy chain: heavy chain: (Reduced) chain: ≥ 90.0% 96.9% chain:97.2% 95.5% 95.7% CE-SDS Main peak: Main peak: Main peak: Main peak: (Non- Main peak ≥ 90.0% 97.8% 98.2% 97.3% 96.6% reduced) ELISA 92% of 100 ^^50% of 98% of reference 98% of reference 92% of reference (Binding reference reference standard standard standard standard Assay) standard Protein 50.0 ^^5.0 mg / mL 49.2 mg / mL 49.2 mg / mL 49.6 mg / mL 49.0 mg / mLConcentration Table 22. Accelerated Stability Data for Exploratory Specification for Clinical Lot 201903038 at 25 ± 2 °C / 60 ± 5% RH Test T0 1 Month 3 Months 6 MonthsCell-based Assay 117% 129% 108% 122%Tables 23 to 28 summarize the available long-term data for the non-clinical lot 201901004 andclinical lot 201903038. Table 23. Long-term Stability Data for Non-Clinical Lot 201901004 at 5 ± 3 °C Test T0 3 Months 6 Months 9 MonthsColor B7 B7 B7 B7Clarity 5.3 NTU 5.5 NTU 5.9 NTU 6.0 NTUVisible No visible particles No visible particles No visible particles No visible particles Particle present present present present ≥25 µm: ≥ 25 µm: ≥ 25 µm: ≥ 25 µm:Sub-visible0 particles / container; 4 particles / container 3 particles / container 1 particles / containerParticles≥ 10 µm: ≥ 10 µm: ≥ 10 µm: 6 ≥ 10 µm2 particles / container; 8 particles / container; 6 particles / container; 15 particles / container; ≥5 µm: 44 ≥ 5 µm: ≥ 5 µm: ≥ 5 µm:particles / container; 19 particles / container 54 particles / container 44 particles / container ≥2 µm: ≥ 2 µm: ≥ 2 µm: 465 ≥ 2 µm:346 335 465 426 pH 5.8 5.9 5.8 5.8pI: 9.3; pI: 9.3; pI: 9.3; pI: 9.3;iCIEFMain peak: 63.9%; Main peak: 60.8%; Main peak: 62.8%; Main peak: 66.3%;Acidic peaks: 28.6%; Acidic peaks: 31.4%; Acidic peaks: 29.2%; Acidic peaks: 26.1%; Basic peak: 7.5% Basic peaks: 7.8% Basic peak: 8.1% Basic peaks: 7.5% Monomer: 99.1%; Monomer: 99.0%; Monomer: 99.0%; Monomer: 98.9%;SEC- HPLCHMWS:0.8%; HMWS:0.9%; HMWS:0.9%; HMWS:1.0%; LMWS: 0.0% LMWS: 0.1% LMWS: 0.1% LMWS: 0.1% CE-SDSLight chain: 29.2%; Light chain: 30.6%; Light chain: 30.1%; Light chain30.4%;:Heavy chain: 68.6%; Heavy chain: 67.0%; Heavy chain: 66.7%; Heavy chain: 66.8%; (Reduced) Minor species: 2.2%; Minor species: 2.4%; Minor species: 3.2%; Minor species: 2.8%; Purity: 97.8% Purity: 97.6% Purity: 96.8% Purity: 97.2%Test T0 3 Months 6 Months 9 MonthsTotal pre-peaks: Total pre-peaks: Total pre-peaks: Total pre- CE-SDS 1.4%;: 1.5%; Total 1.6%; Total peaks:1.6%; Total (Non- Total aggregates: aggregates: 0.4%; aggregates: 0.2%; aggregates: 0.3%; reduced) 0.4%; Purity: 98.2% Purity: 98.2% Purity: 98.1% CCITPuritPy:as9s8.2%NT NT NTELISA96% relative potency 124% relative 88% relative potency 99% relative potency(Binding potency Protein49.9 mg / mL 50.3 mg / mL 50.7 mg / mL 49.8 mg / mLConc. Polysorbate0.031% (w / v) NT 0.031% (w / v) NT80 Table 24. Long-term Stability Data for Non-Clinical Lot 201901004 at 5 ± 3 °C Test 11 Months 12 Months 15 Months 18 MonthsColor B7 B7 B7 B7Clarity 6.1 NTU 5.5 NTU 5.3 NTU 6.0 NTUVisible No visible particles No visible particles No visible particles No visible particles Particle present present present present ≥25 µm: 0 ≥ 25 µm: 1 ≥ 25 µm: ≥ 25 µm:particles / container 1 particles / container 3 particles / container 0 particles / container≥ 10 µm: 16 ≥ 10 µm: 4 ≥ 10 µm: 13 ≥ 10 µm:Sub- visible16 4 particles / container; 13 particles / container 2 particles / container; particles / container Particles ≥ 5 µm: ≥ 5 µm: ≥ 5 µm: 4949 ≥ 5 µm: 114 46 particles / container 84 particles / container particles / container ≥2 µm ≥ 2 µm: ≥ 2 µm: ≥ 2 µm:716 525685 particles / container 484particles / container particles / container particles / container pH 5.9 5.9 5.8 5.9pI: 9.3; pI: 9.3; pI: 9.3; pI: 9.2;iCIEFMain peak63.8%; Main peak: 61.5%; Main peak: 60.8%; Main peak: 60.5%;Acidic peaks: Acidic peaks: 31.0%; Acidic peaks: 31.8%; Acidic peaks: 31.5%; 29.0%; Basic peaks: Basic peaks: 7.5% Basic peaks: 7.3% Basic peaks: 8.0%Test 11 Months 12 Months 15 Months 18 MonthsMonomer: 99.0%; Monomer: 99.0%; Monomer: 98.9%; Monomer:98.9%; SEC- HPLCHMWS:0.9%; HMWS:0.9%; HMWS:1.0%; HMWS: 1.0%; LMWS: 0.1% LMWS: 0.1% LMWS: 0.1% LMWS: 0.1% Light chain: 32.0%; Light chain: 30.9%; Light chain: 31.7%; Light chain: 31.6%;Heavy chain: Heavy chain: 66.5%; Heavy chain: 65.6%; Heavy chain: 65.7%; CE-SDS 65.2%; Minor species: 2.6%; Minor species: 2.7%; Minor species: 2.7%; (Reduced) Purity: 97.2% Purity: 97.4% Purity: 97.3% Purity: 97.3%Total pre-peaks: Total pre-peaks: Total pre-peaks: 2.1%; Total pre-peaks: CE-SDS 1.7%; Total 1.7%; Total Total aggregates: 0.2%; 1.7%; Total (Non- aggregates: 0.3%; aggregates: 0.3%; Purity: 97.7% aggregates: 0.3%; reduced) Purity: 98.0% Purity: 97.9% Purity: 97.9% CCIT NT Pass NT NTELISA 103% relative 111% relative84% relative potency 91% relative potency(Binding potency potencyProtein Conc. 49.8 mg / mL 49.8 mg / mL 50.5 mg / mL 51.8 mg / mLPolysorbateNT 0.030% (w / v) NT NT80 Table 25. Long-term Stability Data for Exploratory Specification for Non-Clinical Lot 201901004 at 5 ± 3 °CTest T0 3 Months6 Months9 Months11 Months 12 Months 15 Months 18 MonthsCell-based 129% 110% 101% 113% 126% 128% 144% 136%Table 26. Long-term Stability Data for Clinical Lot 201903038 at 5 ± 3 °C Test Acceptance Criteria T0 3 Months 6 MonthsColor Not more colored B7 B6 B7than B4 Clarity ≤ 18 NTU 5.9 NTU 6.7 NTU 6.2 NTULiquid, essentially Liquid, essentially Liquid, essentially Liquid, essentially Visible Particle free of visible free of visible free of visible free of visible particles particles particles particlesTest Acceptance Criteria T0 3 Months 6 Months≥ 10 µm: ≤ 6000 ≥ 10 µm: 9 ≥ 10 µm: 0 ≥ 10 µm: 98Sub-visible particles / container particles / container particles / container particles / container Particles ≥ 25 µm: ≤ 600 ≥ 25 µm: 0 ≥ 25 µm: 0 ≥ 25 µm: 43 particles / container particles / container particles / container particles / containerpH 5.8 ^^0.5 5.8 5.8 5.8Main peak% ≥ 50.0% Main peak%: 64.7% Main peak%: 62.2% Main peak%: 62.9% iCIEF Acidic peaks% Acidic peaks%: Acidic peaks%: Acidic peaks%: ≤ 40.0% 29.4% 32.3% 31.8% Basic peaks% ≤ Basic peaks%: 6.0% Basic peaks%: 5.5% Basic peaks%: 5.3% 15.0% Main peak Monomer: 99.3% Monomer: 99.2% Monomer: 99.3% SEC-HPLC (monomer) ≥ 95.0% HMWS: 0.6% HMWS: 0.7% HMWS: 0.7% HMWS% ≤ 5.0% LMWS: 0.0% LMWS: 0.1% LMWS: 0.1% Report LMWS% CE-SDS Light chain + heavy Light chain + heavy Light chain + heavy Light chain + heavy (Reduced) chain: ≥ 90.0% chain: 96.9% chain: 96.8% chain: 97.4% CE-SDS(Non-reduced) Main peak ≥ 90.0% Main peak: 97.8% Main peak: 98.4% Main peak: 98.5%ELISA 100 ^^50% of 98% of reference 116% of reference 98% of reference (Binding reference standard standard standard standard ProAtesinsaCy)onc. 50.0 ^^5.0 mg / mL 49.2 mg / mL 49.1 mg / mL 48.8 mg / mLCCIT Pass Passed Not tested Not testedTable 27. Long-term Stability Data for Clinical Lot 201903038 at 5 ± 3 °CTest Acceptance Criteria 9 Months 12 MonthsColor Not more colored than B4 B7 B7Clarity ≤ 18 NTU 6.3 NTU 6.5 NTULiquid, essentially free of Liquid, essentially free Liquid, essentially free of Visible Particle visible particles of visible particles visible particles ≥10 µm: ≤ 6000 ≥ 10 µm: 6 ≥ 10 µm: 10particles / container particles / container particles / container ≥ 25 µm: ≤ 600 ≥ 25 µm: 1 ≥ 25 µm: 0Test Acceptance Criteria 9 Months 12 MonthsSub-visibleparticles / container particles / container particles / containerParptiHcles 5.8 ^^0.5 5.8 5.8Main peak% ≥ 50.0% Main peak%: 62.7% Main peak%: 61.2% Acidic iCIEF Acidic peaks% ≤ 40.0% Acidic peaks%: 32.2% peaks%: 33.9% Basic peaks% ≤ 15.0% Basic peaks%: 5.2% Basic peaks%: 4.9% Main peak (monomer) ≥ Monomer: 99.2% Monomer: 99.2% SEC-HPLC 95.0% HMWS: 0.7% HMWS: 0.6% HMWS% ≤ 5.0% LMWS: 0.1% LMWS: 0.2% Report LMWS% CE-SDS Light chain + heavy Light chain + heavy Light chain + heavy chain: (Reduced) chain: ≥ 90.0% chain: 96.7% 96.9% CE-SDS (Non-reduced) Main peak ≥ 90.0% Main peak: 98.3% Main peak: 98.5%ELISA 100 ^^50% of reference 109% of reference 98% of refe...

Claims

Claims1. A composition comprising one or more antibodies comprising an immunoglobulinheavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8,wherein SEQ ID NO: 9 comprises the sequence: QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein in one or more of the antibodies,the glutamine (Q) at position 1 is modified to pyroglutamate (pE),the lysine (K) at position 450 is absent, andthe asparagine (N) at position 300 is glycosylated, and wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the antibodies comprise the following glycan types: Man3+1F, G0-GN, G0F- GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2.

2. A composition comprising one or more antibodies comprising an immunoglobulinheavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8,wherein SEQ ID NO: 9 comprises the sequence: QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVKDYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein in one or more of the antibodies,the glutamine (Q) at position 1 is modified to pyroglutamate (pE),the lysine (K) at position 450 is absent, andthe asparagine (N) at position 300 is glycosylated, and wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein less than 3% of the glycans are of the Man5 type.

3. A composition comprising one or more antibodies comprising an immunoglobulinheavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8,wherein SEQ ID NO: 9 comprises the sequence: QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein in one or more of the antibodies,the glutamine (Q) at position 1 is modified to pyroglutamate (pE),the lysine (K) at position 450 is absent, andthe asparagine (N) at position 300 is glycosylated,and wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the antibodies comprise the following glycan types: Man3+1F, G0-GN, G0F- GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2 andwherein less than 3% of the glycans are of the Man5 type.

4. The composition of any one of claims 1 to 3, wherein the major glycan types are G0Fand G1F.

5. The composition of claim 4, wherein about 49% of the glycans are of the G0F type andabout 25% of the glycans are of the G1F type.

6. The composition of any one of claims 1 to 5, which comprises the following chargevariants of the antibodies: Main peak ≥ 50.0% Acidic peaks ≤ 40.0% Basic peaks ≤ 15.0%.

7. The composition of any one of claims 1 to 6, which comprises the following chargevariants of the antibodies: Main peak ≥ 63.0% Acidic peaks ≤ 32.0% Basic peaks ≤ 5.0%.

8. The composition of any one of claims 1 to 7, wherein the antibodies are comprised inan aqueous formulation, wherein the formulation comprises the antibodies at aconcentration of about 50 mg / ml or about 100 mg / ml and histidine at a concentration of about 20 mM, sucrose at a concentration of about 6.5% weight per volume (w / v) orabout 8% (w / v) sucrose, and PS80 at a concentration of about 0.03% w / v, wherein the formulation has a pH of about 5.8.

9. The composition of any one of claims 1 to 8, wherein the formulationhas a content of acidic species of the antibodies of ≤ 40.0% and of basic species of theantibodies of ≤ 15.0% after 6 months storage at 5 ± 3 °C as determined by iCIEF; and / or has a content of high molecular weight species of ≤ 5.0% after 6 months storage at 5 ±3 °C as determined by SEC-HPLC.

10. The composition of any one of claims 1 to 9, wherein the antibodies are obtainable by amethod which includes culturing CHO-K1 cells comprising one or more polynucleotides comprising a nucleotide sequence encoding an immunoglobulin heavychain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8 or one or morevectors comprising the polynucleotide(s) in Chinese hamster ovary (CHO)-K1 cells, and isolating the antibodies from the cell culture.

11. The composition of claim 10, wherein the method includes cultivation of the CHO-K1cells with a pH dead band of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15, preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably of 0.05 or 0.1, most preferably of 0.05.

12. The composition of any one of claims 1 to 11, wherein in one or more of the antibodies,the asparagine (N) at position 58 is deamidatedthe methionine (M) at position 71 is oxidized, the methionine (M) at position 115 is oxidized the methionine (M) at position 255 is oxidized the aspartate (D) at position 283 is iso-aspartate; the asparagine (N) as position 318 is deamidated or comprises a succinimide;the methionine (M) at position 361 is oxidized the asparagine (N) at position 387 is deamidated or comprises a succinimide;the methionine (M) at position 431 is oxidizedthe proline (P) at position 448 is amidated; and / orthe glycine (G) at position 449 is absent.

13. The composition of any one of claims 1 to 12, wherein in more than 90%, preferably inabout 99% to 100% of the antibodies the glutamine (Q) at position 1 of SEQ ID NO: 9is modified to pyroglutamate, and / or wherein in more than 90%, preferably in about95% to 100%, preferably in about 95% to 96% of the antibodies the lysine (K) at position 450 of SEQ ID NO: 9 is absent.

14. The composition of any one of claims 1 to 13, wherein more than 85% of the glycansare fucosylated, preferably wherein about 85% to 95% of the glycans are fucosylated.

15. The composition of any one of claims 1 to 14, wherein about 20% to 40% of the glycansare galactosylated.

16. The composition of any one of claims 1 to 15, wherein about 80% to 90% of the glycansare part of the major fucosylated glycan types.

17. The composition of any one of claims 1 to 16, wherein about 1% to 4% of the glycansare mannose-containing glycans, preferably wherein the glycans are of the Man5 and Man31F type.

18. The composition of any one of claims 1 to 17, wherein about 1% to 4% of the glycansare of the Man5 type, preferably 1% to 3%, more preferably 1% to 2%.

19. The composition of any one of claims 1 to 18, wherein less than 2% of the glycans aresiaylated, preferably wherein about 0.5% to 2% of the glycans are siaylated.

20. The composition of any one of claims 1 to 19, wherein in one or more of the antibodies,the asparagine (N) at position 58, at position 318, and / or at position 387 of SEQ ID NO: 9 is deamidated.

21. The composition of any one of claims 1 to 20, wherein in less than 5%, preferably inless than 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the asparagine (N) at position 58 of SEQ ID NO: 9 is deamidated.

22. The composition of any one of claims 1 to 21, wherein in less than about 9%, preferablyin less than about 8%, preferably in about 6% to 9% of the antibodies, the asparagine (N) at position 318 of SEQ ID NO: 9 is deamidated.

23. The composition of any one of claims 1 to 22, wherein in less than about 5%, preferablyin less than about 3%, preferably in about 1% to 43% of the antibodies, the asparagine (N) at position 387 of SEQ ID NO: 9 is deamidated.

24. The composition of any one of claims 1 to 23, wherein in one or more of the antibodies,the methionine at position 71, at position 115, at position 255, at position 361, and / or at position 431 of SEQ ID NO: 9 is oxidized.

25. The composition of any one of claims 1 to 24, wherein in less than about 5%, preferablyin less than about 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the methionine (M) at position 71 of SEQ ID NO: 9 is oxidized.

26. The composition of any one of claims 1 to 25, wherein in less than about 5%, preferablyin less than about 3%, preferably in less than about 2, preferably in about 1% to 3% of the antibodies, the methionine (M) at position 115 of SEQ ID NO: 9 is oxidized.

27. The composition of any one of claims 1 to 26, wherein in less than about 5%, preferablyin less than about 3%, preferably in about 1% to 30% of the antibodies, the methionine (M) at position 255 of SEQ ID NO: 9 is oxidized.

28. The composition of any one of claims 1 to 27, wherein in less than about 5%, preferablyin less than about 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the methionine (M) at position 361 of SEQ ID NO: 9 is oxidized.

29. The composition of any one of claims 1 to 28, wherein in less than about 5%, preferablyin less than about 3%, preferably in less than about 2%, preferably in about 1% to 2% of the antibodies, the methionine (M) at position 431 of SEQ ID NO: 9 is oxidized.

30. The composition of any one of claims 1 to 29, wherein in one or more of the antibodies,the aspartate (D) at position 283 of SEQ ID NO: 9 is modified to iso-aspartate.

31. The composition of any one of claims 1 to 30, wherein in one or more of the antibodies,the proline (P) at position 448 of SEQ ID NO: 9 is amidated.

32. The composition of any one of claims 1 to 31, wherein in one or more of the antibodies,the glycine (G) at position 449 of SEQ ID NO: 9 is absent.

33. The composition of any one of claims 1 to 32, wherein one or more of the antibodiesare fragmented via clipping between asparagine at position 58 and threonine at position 59 of SEQ ID NO: 9.

34. The composition of any one of claims 1 to 33, wherein in one or more of the antibodiesthe light chain (LC) and / or the heavy chain (HC) is glycated, preferably wherein (i) in less than about 35%, preferably in less than about 2%, preferably in about 1%to 3% of the antibodies, the LC is glycated; and / or (ii) in less than about 6%, preferably in less than about 5%, preferably in about 2%to 5% of the antibodies, the HC is glycated.

35. The composition of any one of claims 1 to 32, wherein the antibodies comprise a firstHC (HC1), a first LC (LC1), a second HC (HC2), and a second LC (LC2).

36. The composition of claim 35, wherein the antibodies comprise one or more of thefollowing disulfide bridges: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in SEQ ID NOs: 8 and 9.

37. The composition of any one of claims 1 to 36, wherein the antibodies(i) have a molecular weight of 147.0 to 147.6 kDa:(ii) have a pI of 8.4 (theoretically) and 9.3 (determined), respectively; and / or(iii) have an extinction coefficient (A0.1%) (mL / (mg * cm)) of 1.39 (theoretically) and1.438 (experimentally determined), respectively.

38. The composition of any one of claims 1 to 37, wherein the one or more antibodies areacidic variants.

39. The composition of any one of claims 1 to 38, wherein the antibodies are recombinantantibodies produced in Chinese hamster ovary (CHO) cells, preferably in CHO-K1 cells.

40. The composition of any one of claims 1 to 39, wherein the HC of the antibodies furthercomprises a signal peptide, which is derived from a human immunoglobulin heavy chain, and wherein the LC further comprises a signal peptide which is derived from a human immunoglobulin kappa light chain, preferably wherein the signal peptide of the HC has the amino acid sequence set forth in SEQ ID NO: 17, and the signal peptide of the LC has the amino acid sequence set forth in SEQ ID NO: 18.

41. The composition of claim 40, wherein the HC including the signal peptide has the aminoacid set forth in SEQ ID NO: 19 and wherein the LC including the signal peptide has the amino acid sequence set forth in SEQ ID NO: 20.

42. A composition comprising one or more antibodies comprising an immunoglobulinheavy chain (HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8,wherein SEQ ID NO: 9 comprises the sequence: QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein in one or more of the antibodies,the glutamine (Q) at position 1 is modified to pyroglutamate (pE),the lysine (K) at position 450 is absent, andthe asparagine (N) at position 300 is glycosylated, and wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the antibodies comprise the following glycan types: Man3+1F, G0-GN, G0F- GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2, and wherein the antibodies are recombinant antibodies produced in Chinese hamster ovary(CHO)-K1 cells.

43. An antibody comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the aminoacid sequence of SEQ ID NO: 8, wherein SEQ ID NO: 9 comprises the sequence:QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the HC comprises the following modifications:the glutamine (Q) at position 1 is modified to pyroglutamate; the lysine (K) at position 450 is deleted; and the asparagine (N) at position 300 is glycosylated, andwherein the antibody comprises the following glycan types: Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2.

44. An antibody comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the aminoacid sequence of SEQ ID NO: 8, wherein SEQ ID NO: 9 comprises the sequence:QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK, wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the HC comprises the following modifications:the glutamine (Q) at position 1 is modified to pyroglutamate; the lysine (K) at position 450 is deleted; and the asparagine (N) at position 300 is glycosylated, and wherein less than 3% of the glycans are of the Man5 type.

45. The antibody of claim 43 or 44, wherein the HC further comprises one or more of thefollowing modifications: the asparagine (N) at position 58 is deamidated; the methionine (M) at position 71 is oxidized; the methionine (M) at position 115 is oxidized; the methionine (M) at position 255 is oxidized; the aspartate (D) at position 283 is isomerized; the asparagine (N) at position 318 is deamidated or comprises a succinimide; the methionine (M) at position 361 is oxidized;the asparagine (N) at position 387 is deamidated or comprises a succinimide; the methionine (M) at position 431 is oxidized; the glycine (G) at position 449 is absent; the proline (P) at position 448 is amidated after the loss of the C-terminal lysine and glycine.

46. The antibody of any one of claims 43 to 45, wherein the major glycan types are G0Fand G1F, preferably wherein about 49% of the glycans are of the G0F type and about25% of the glycans are of the G1F type.

47. An antibody comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 7 and an immunoglobulin light chain (LC) having the aminoacid sequence of SEQ ID NO: 8, wherein SEQ ID NO: 7 comprises the sequence: X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSG NTYDNPSLKSRLTMSVDTSKNQFSLNLRSVTAADTAVYYCARIVPGGDAFDIWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLX2ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESX4GQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSX5X6X7 wherein: X1is absent, glutamine, or a pyroglutamate (pE); X2 is methionine or oxidized methionine; X3is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine or deamidated asparagine; X5 is proline or amidated proline; X6is absent or glycine; and X7is absent or lysine; and wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC.

48. The antibody of claim 47, wherein the HC has the amino acid sequence of SEQ ID NO:39 comprising the sequence:X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSG XITYDNPSLKSRLTXIISVDTSKNQFSLNLRSVTAADTAVYYCARIVPGGDAFDIWGQG TXIIIVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLX2ISRTPEVTCVVVDVSHEDPEVKFNWYVXIV GVEVHNAKTKPREEQYXVSTYRVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSREEXVITKNQVSLTCLVKGFYPSDIAVEWESX4GQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVXVIIHEALHNHYTQKSLSLSX5X6X7wherein: X1 is absent, glutamine, or a pyroglutamate (pE); X2is methionine or oxidized methionine; X3is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X5 is proline or amidated proline; X6is absent or glycine; X7 is absent or lysine; XI is asparagine or deamidated asparagine; XIIis methionine or oxidized methionine; XIIIis methionine or oxidized methionine; XIV is aspartate or iso-aspartate; XVis asparagine or glycosylated asparagine; XVIis methionine or oxidized methionine; and XVII is methionine or oxidized methionine.

49. The antibody of claim 47 or 48, wherein X1is pyroglutamate (pE).

50. The antibody of claim 47 or 48, wherein X1 is glutamine.

51. The antibody of any one of claims 47 to 50, wherein X7 is absent.

52. The antibody of any one of claims 47 to 50, wherein X7 is lysine.

53. The antibody of claim 51, wherein X6 is absent.

54. The antibody of any one of claims 47 to 52, wherein X6 is glycine.

55. The antibody of any one of claims 47 to 54, wherein X5 is amidated proline.

56. The antibody of any one of claims 47 to 54, wherein X5 is proline.

57. The antibody of any one of claims 47 to 56, wherein X2 is oxidized methionine.

58. The antibody of any one of claims 47 to 56, wherein X2 is methionine.

59. The antibody of any one of claims 47 to 58, wherein X3 is deamidated asparagine.

60. The antibody of any one of claims 47 to 58, wherein X3 comprises an asparaginecomprising a succinimide.

61. The antibody of any one of claims 47 to 58, wherein X3 is asparagine.

62. The antibody of any one of claims 47 to 61, wherein X4 is deamidated asparagine.

63. The antibody of any one of claims 47 to 61, wherein X4 comprises an asparaginecomprising a succinimide.

64. The antibody of any one of claims 47 to 61, wherein X4 is asparagine.

65. The antibody of any one of claims 48 to 64, wherein XI is deamidated asparagine.

66. The antibody of any one of claims 48 to 64, wherein XI is asparagine.

67. The antibody of any one of claims 48 to 66, wherein XII is oxidized methionine.

68. The antibody of any one of claims 48 to 66, wherein XII is methionine.

69. The antibody of any one of claims 48 to 68, wherein XIII is oxidized methionine.

70. The antibody of any one of claims 48 to 68, wherein XIII is methionine.

71. The antibody of any one of claims 48 to 70, wherein XIV is iso-aspartate.

72. The antibody of any one of claims 48 to 70, wherein XIV is aspartate.

73. The antibody of any one of claims 48 to 72, wherein XV is glycosylated asparagine.

74. The antibody of any one of claims 48 to 72, wherein XV is asparagine.

75. The antibody of any one of claims 48 to 74, wherein XVI is oxidized methionine.

76. The antibody of any one of claims 48 to 74, wherein XVI is methionine.

77. The antibody of any one of claims 48 to 76, wherein XVII is oxidized methionine.

78. The antibody of any one of claims 48 to 76, wherein XVII is methionine.

79. The antibody of any one of claims 47 to 78, wherein X1 is pyroglutamate (pE), X2 ismethionine, X3 is asparagine, X4 is asparagine, X5 is proline, X6 is glycine, and X7 is absent.

80. The antibody of any one of claims 48 to 79,wherein X1is pyroglutamate (pE), X2is methionine, X3is asparagine, X4is asparagine, X5 is proline, X6 is glycine, X7 is absent, XI is asparagine, XII is methionine, XIII is methionine, XIV is aspartate, XV is glycosylated asparagine, XVI is methionine, and XVII is methionine; or wherein X1is pyroglutamate (pE), X2is oxidized methionine, X3is asparagine, X4is asparagine, X5 is proline, X6 is glycine, X7 is absent, XI is asparagine, XII is methionine, XIIIis oxidized methionine, XIVis aspartate, XVis glycosylated asparagine, XVIis methionine, and XVIIis methionine.

81. The antibody of any one of claims 42 to 80, wherein the antibody comprises a glycatedlight chain (LC).

82. The antibody of any one of claims 42 to 81, wherein the antibody comprises a glycatedheavy chain (HC).

83. The antibody of any one of claims 42 to 82, wherein the antibody comprises a first HC(HC1), a first LC (LC1), a second HC (HC2), and a second LC (LC2).

84. The antibody of claim 83, wherein the antibody comprises one or more of the following disulfide bridges: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in SEQ ID NOs: 7 and 8 in which the glutamine (X1) is present in SEQ ID NO: 7 and inSEQ ID NOs: 9 and 8, respectively.

85. The antibody of any one of claims 42 to 84, wherein the antibody has a molecular weightof 147.0 to 147.6 kDa.

86. The antibody of any one of claims 42 to 85, wherein the antibody has a pI of 8.4(theoretically) and 9.3 (experimentally determined), respectively.

87. The antibody of any one of claims 42 to 86, wherein the antibody has an extinctioncoefficient (A0.1%) (mL / (mg * cm)) of 1.39 (theoretically) and 1.438 (experimentallydetermined), respectively.

88. The antibody of any one of claims 42 to 87, wherein the antibody is an acidic antibodyvariant.

89. The antibody of any one of claims 42 to 88, wherein the constant region of each HCcontains one N-linked glycan site at residue N300 as set forth in SEQ ID NO: 7 or 9.

90. The antibody of claim 89, wherein the antibody comprises one or more of the followingglycan types: Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2, preferably wherein the major glycan types are G0F and G1F.

91. The antibody of claim 89 or 90, wherein more than 85% of the glycans are fucosylated,preferably wherein about 85% to 95% of the glycans are fucosylated.

92. The antibody of any one of claims 89 to 91, wherein about 20% to 40% of the glycansare galactosylated.

93. The antibody of any one of claims 89 to 92, wherein about 80% to 90% of the glycansare part of the major fucosylated glycan types, preferably wherein the major glycan types are G0F and G1F.

94. The antibody of any one of claims 89 to 94, wherein about 1% to 4% of the glycans aremannose containing glycans, preferably wherein the glycans are of the Man5 and Man31F type.

95. The antibody of any one of claims 89 to 94, wherein about 1% to 4% of the glycans areof the Man5 type.

96. The antibody of any one of claims 89 to 95, wherein less than about 3% of the glycansare of the Man5 type, preferably about 1% to 2.5%, preferably about 1% to 2% of the glycans are of the Man5 type.

97. The antibody of any one of claims 89 to 96, wherein less than 2% of the glycans aresiaylated, preferably wherein about 0.5% to 2% of the glycans are siaylated.

98. The antibody of any one of claims 42 to 87, wherein the antibody is a recombinantantibody produced in Chinese hamster ovary (CHO) cells, preferably wherein theantibody is produced in CHO-K1 cells.

99. An antibody comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the aminoacid sequence of SEQ ID NO: 8, wherein SEQ ID NO: 9 comprises the sequence:QLQLQESGPG LVKPSETLSL TCSVSGGSII SRSSYWGWIR QPPGKGLEWI GGIYHSGNTY DNPSLKSRLT MSVDTSKNQF SLNLRSVTAA DTAVYYCARI VPGGDAFDIW GQGTMVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK wherein: the glutamine (Q) at position 1 is modified to pyroglutamate; the lysine (K) at position 450 is deleted; and the asparagine (N) at position 300 is glycosylated; and wherein the antibody comprises the following disulfide bridges: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in SEQ ID NOs:8 and 9; and wherein the antibody comprises the following glycan types: Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2, preferably wherein the major glycan types are G0F and G1F.wherein SEQ ID NO: 8 comprises the sequence: DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC.

100. The antibody of claim 99, wherein less than 3% of the glycans are of the Man5 type.

101. The antibody of claim 99 or 100, wherein the HC further comprises one or more of thefollowing modifications: the asparagine (N) at position 58 is deamidated; the methionine (M) at position 71 is oxidized; the methionine (M) at position 115 is oxidized; the methionine (M) at position 255 is oxidized; the aspartate (D) at position 283 is isomerized; the asparagine (N) at position 318 is deamidated or comprises a succinimide; the methionine (M) at position 361 is oxidized; the asparagine (N) at position 387 is deamidated or comprises a succinimide; the methionine (M) at position 431 is oxidized; the glycine (G) at position 449 is absent; the proline (P) at position 448 is amidated after the loss of the C-terminal lysine and glycine; the lysine (K) residues are glycated.

102. The antibody of any one of claims 42 to 101, wherein the HC further comprises a signalpeptide, which is derived from a human immunoglobulin heavy chain, and wherein the LC further comprises a signal peptide which is derived from a human immunoglobulin kappa light chain, preferably wherein the signal peptide of the HC has the amino acid sequence set forth in SEQ ID NO: 17, and the signal peptide of the LC has the amino acid sequence set forth in SEQ ID NO: 18, preferably wherein the HC including the signal peptide has the amino acid set forth in SEQ ID NO: 19 and wherein the LC including the signal peptide has the amino acid sequence set forth in SEQ ID NO: 20.

103. An antibody comprising an immunoglobulin heavy chain (HC) having the amino acidsequence of SEQ ID NO: 7 and an immunoglobulin light chain (LC) having the aminoacid sequence of SEQ ID NO: 8, wherein SEQ ID NO: 7 comprises the sequence:X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSG NTYDNPSLKSRLTMSVDTSKNQFSLNLRSVTAADTAVYYCARIVPGGDAFDIWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLX2ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESX4GQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSX5X6X7 wherein: X1is absent, glutamine, or a pyroglutamate (pE); X2 is methionine or oxidized methionine; X3is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4is asparagine or deamidated asparagine; X5 is proline or amidated proline; X6 is absent or glycine; and X7is absent or lysine; and wherein SEQ ID NO: 8 comprises the sequence:DIQMTQSPSSLSASVGDRVTIACRASQSVGTYLNWYQQKRGKAPKLLIFAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein the HC further comprises a signal peptide, which is derived from a human immunoglobulin heavy chain, and wherein the LC further comprises a signal peptide which is derived from a human immunoglobulin kappa light chain, preferably wherein the signal peptide of the HC has the amino acid sequence set forth in SEQ ID NO: 17, and the signal peptide of the LC has the amino acid sequence set forth in SEQ ID NO: 18.

104. The antibody of claim 103, wherein the HC has the amino acid sequence of SEQ IDNO: 39 comprising the sequence:X1LQLQESGPGLVKPSETLSLTCSVSGGSIISRSSYWGWIRQPPGKGLEWIGGIYHSG XITYDNPSLKSRLTXIISVDTSKNQFSLNLRSVTAADTAVYYCARIVPGGDAFDIWGQGTXIIIVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLX2ISRTPEVTCVVVDVSHEDPEVKFNWYVXIV GVEVHNAKTKPREEQYXVSTYRVVSVLTVLHQDWLX3GKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSREEXVITKNQVSLTCLVKGFYPSDIAVEWESX4GQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVXVIIHEALHNHYTQKSLSLSX5X6 X7wherein: X1 is absent, glutamine, or a pyroglutamate (pE); X2is methionine or oxidized methionine; X3 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X4 is asparagine, deamidated asparagine, or asparagine comprising a succinimide; X5is proline or amidated proline; X6is absent or glycine; X7 is absent or lysine; XI is asparagine or deamidated asparagine;XIIis methionine or oxidized methionine; XIII is methionine or oxidized methionine; XIV is aspartate or iso-aspartate; XVis asparagine or glycosylated asparagine; XVI is methionine or oxidized methionine; and XVII is methionine or oxidized methionine.

105. The antibody of claim 103 or 104, wherein the HC including the signal peptide has theamino acid set forth in SEQ ID NO: 19 and wherein the LC including the signal peptide has the amino acid sequence set forth in SEQ ID NO: 20.

106. One or more polynucleotide(s) comprising a nucleotide sequence encoding theimmunoglobulin heavy chain (HC) and immunoglobulin light chain (LC) of an anti- transthyretin (TTR) antibody, wherein the HC has the amino acid sequence of SEQ ID NO: 7, 9, or 39 and the LC has the amino acid sequence of SEQ ID NO: 8.

107. A nucleic acid molecule which is(a) polynucleotide(s) comprising a first nucleotide sequence set forth in SEQ ID NO: 13, which encodes the immunoglobulin heavy chain (HC) of an anti-transthyretin (TTR) antibody and a second nucleotide sequence set forth in SEQ ID NO: 14, which encodesthe immunoglobulin light chain (LC) of an anti-transthyretin (TTR) antibody; (b) messenger RNA (mRNA) equivalent of the first and the second nucleotide sequences of (a); (c) polynucleotide(s) comprising sequences which are complementary to the first and the second nucleotide sequences of (a) or the mRNA equivalent thereof of (b); or (d) polynucleotide(s) comprising sequences which are degenerates of the first and the second nucleotide sequences of (a) or the mRNA equivalent thereof of (b).

108. The nucleic acid molecule of claim 107, wherein the sequence of the degenerate of thefirst nucleotide sequence is set forth in SEQ ID NO: 15 and wherein the sequence of the degenerate of the second nucleotide sequence is set forth in SEQ ID NO: 16.

109. The polynucleotide(s) of claim 106 or the nucleic acid molecule of claim 107 or 108,wherein the first nucleotide sequence comprises a nucleotide sequence encoding a first signal peptide derived from a human immunoglobulin heavy chain and the second nucleotide sequences comprises a nucleotide sequence encoding a second signal peptide derived from a human immunoglobulin kappa light chain, preferably wherein the nucleotide sequence of the first signal peptide is set forth in SEQ ID NO: 21, and the nucleotide sequence of the second signal peptide is set forth in SEQ ID NO: 22.

110. The polynucleotide(s) or the nucleic acid molecule of claim 109, wherein the firstnucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 23, and wherein the second nucleotide sequence including the nucleotide sequence of the signal peptide has the sequence set forth in SEQ ID NO: 24.

111. One or more polynucleotide(s) comprising a first nucleotide sequence encoding theimmunoglobulin heavy chain (HC) and a second nucleotide sequence encoding the immunoglobulin light chain (LC) of an anti-transthyretin (TTR) antibody, wherein the HC has the amino acid sequence of SEQ ID NO: 7, 9, or 39 and the LC has the amino acid sequence of SEQ ID NO: 8, wherein the first nucleotide sequence comprises anucleotide sequence encoding a first signal peptide derived from a human immunoglobulin heavy chain and the second nucleotide sequences comprises a nucleotide sequence encoding a second signal peptide derived from a human immunoglobulin kappa light chain, preferably wherein the nucleotide sequence of the first signal peptide is set forth in SEQ ID NO: 21, and the nucleotide sequence of the second signal peptide is set forth in SEQ ID NO: 22.

112. A nucleic acid molecule which is polynucleotide(s) comprising a first nucleotidesequence set forth in SEQ ID NO: 13, which encodes the immunoglobulin heavy chain (HC) of an anti-transthyretin (TTR) antibody and a second nucleotide sequence set forthin SEQ ID NO: 14, which encodes the immunoglobulin light chain (LC) of an anti- transthyretin (TTR) antibody, wherein the first nucleotide sequence comprises a nucleotide sequence encoding a first signal peptide derived from a human immunoglobulin heavy chain and the second nucleotide sequences comprises a nucleotide sequence encoding a second signal peptide derived from a human immunoglobulin kappa light chain, preferably wherein the nucleotide sequence of the first signal peptide is set forth in SEQ ID NO: 21, and the nucleotide sequence of the second signal peptide is set forth in SEQ ID NO: 22.

113. One or more expression vector(s) comprising the polynucleotide(s) of any one of claims106 and 109 to 111, or the nucleic acid molecule of any one of claims 107 to 110 and 112.

114. A host cell comprising the polynucleotide(s) of any one of claims 106 and 109 to 111,or the nucleic acid molecule of any one of claims 107 to 110 and 112, or the vector(s) of claim 114.

115. The host cell of claim 114, which is non-human cell, preferably E. coli, insect or CHOcell.

116. The host cell of claim 114 or 115, which is a CHO cell, preferably a CHO-K1 cell.

117. A method of manufacture of an anti-TTR antibody, said method comprising(a) culturing the cell of any one of claims 114 to 116; and(b) isolating the antibody or immunoglobulin chain(s) thereof from the culture.

118. A method for producing the antibody of any one of claims 42 to 105 or an antigen-binding fragment thereof, wherein the antibody comprises as least the following post- translational modifications: X1 and the glutamine (Q) at position 1 of SEQ ID NO: 9, respectively is pyroglutamate (pE), and / or X7 and the lysine (K) at position 450 of SEQ ID NO: 9, respectively, is absent, the method comprising a) cloning the nucleic acid molecule of any one of claims 107 to 110 and 112, which comprises the first nucleotide sequence into an expression vector and cloning the nucleic acid molecule of any one of claims 107 to 110 and 112, which comprises the second nucleotide sequence into an expression vector, wherein the first and the second nucleotide sequences may be provided in the same or different expression vectors; b) transforming the expression vector(s) into CHO-K1 cells; c) culturing the host cell under conditions allowing for the expression of the immunoglobulin chains comprising heavy chain and light chain; d) isolating the immunoglobulin chains and resultant IgG antibody, respectively, from the culture and optionally digesting the IgG antibody to generate antigen- binding fragments of the antibody, e.g., using enzymatic digestion comprising papain cleavage to generate Fab fragments.

119. A method for producing the antibody of any one of claims 42 to 105 or an antigen-binding fragment thereof, wherein the antibody comprises as least the following post- translational modifications: the glutamine (Q) at position 1 of SEQ ID NO: 9 is pyroglutamate (pE),the lysine (K) at position 450 of SEQ ID NO: 9 is absent, andthe asparagine (N) at position 300 of SEQ ID NO: 9 is glycosylated, wherein less than 3% of the glycans are of the Man5 type. the method comprising a) cloning the nucleic acid molecule of any one of claims 107 to 110 and 112, which comprises the first nucleotide sequence into an expression vector and cloning the nucleic acid molecule of any one of claims 107 to 110 and 112, which comprisesthe second nucleotide sequence into an expression vector, wherein the first and the second nucleotide sequences may be provided in the same or different expression vectors; b) transforming the expression vector(s) into CHO-K1 cells; c) culturing the host cell under conditions allowing for the expression of the immunoglobulin chains comprising heavy chain and light chain, wherein cultivation is performed with a pH dead band of 0.1-0.05, preferably of 0.05; d) isolating the immunoglobulin chains and resultant IgG antibody, respectively, from the culture and optionally digesting the IgG antibody to generate antigen- binding fragments of the antibody, e.g., using enzymatic digestion comprising papain cleavage to generate Fab fragments.

120. An antibody encodable by the polynucleotide(s) of any one of claims 106 and 109 to111, or by the vector(s) of claim 113, or obtainable by the method of any one of claims 117 to 119.

121. A composition comprising one or more of the antibodies of any one of claims 42 to 105,and 120.

122. The composition of claim 121, wherein in one or more of the antibodies the glutamine(Q) at position 1 of SEQ ID NO: 9 is modified to pyroglutamate and wherein X1 in SEQID NO: 7 or 39 is pyroglutamate, respectively.

123. The composition of claim 121 or 122, wherein in more than 90%, preferably in about99% to 100% of the antibodies the glutamine (Q) at position 1 of SEQ ID NO: 9 is modified to pyroglutamate and wherein X1 in SEQ ID NO: 7 or 39 is pyroglutamate,respectively.

124. The composition of any one of claims 121 to 122, wherein in one or more of theantibodies, the lysine (K) at position 450 of SEQ ID NO: 9 and the X7in SEQ ID NO: 7 or 39, respectively is absent.

125. The composition of any one of claims 121 to 124, wherein in more than 90%, preferablyin about 95% to 100%, preferably in about 95% to 96% of the antibodies the lysine (K)at position 450 of SEQ ID NO: 9 and the X7 in SEQ ID NO: 7 or 39, respectively isabsent.

126. The composition of any one of claims 121 to 125, wherein the antibodies compriseglycans, preferably N-glycans, preferably wherein the asparagine (N) at position 300 of SEQ ID NO: 9 is glycosylated and the XV in SEQ ID NO: 39 is glycosylated asparagine, respectively.

127. The composition of any one of claims 121 to 126, wherein the antibodies comprise thefollowing glycan types: Man3+1F, G0-GN, G0F-GN, G0, G0F, Man5, G1F-GN / G1a, G1b, G1Fa, G1Fb, G2F, G2FS1, and G2FS2, preferably wherein the major glycan types are G0F and G1F.

128. The composition of claim 126 or 127, wherein more than 85% of the glycans arefucosylated, preferably wherein about 85% to 95% of the glycans are fucosylated.

129. The composition of any one of claims 126 to 128, wherein about 20% to 40% of theglycans are galactosylated.

130. The composition of any one of claims 126 to 129, wherein about 80% to 90% of theglycans are part of the major fucosylated glycan types, preferably wherein the majorglycan types are G0F and G1F.

131. The composition of any one of claims 125 to 130, wherein about 1% to 4% of theglycans are mannose containing glycans, preferably wherein the glycans are of the Man5 and Man31F type132. The composition of any one of claims 125 to 131, wherein less than about 3%,preferably about 1% to 2.5%, preferably 1% to 2% of the glycans are of the Man5 type.

133. The composition of any one of claims 125 to 132, wherein less than 2% of the glycansare siaylated, preferably wherein about 0.5% to 2% of the glycans are siaylated.

134. The composition of any one of claims 121 to 133, wherein in one or more of theantibodies, the asparagine (N) at position 58, at position 318, and / or at position 387 of SEQ ID NO: 9 is deamidated and XI, X3 and / or X4 in SEQ ID NO: 39 is deamidated asparagine, respectively. .

135. The composition of any one of claims 121 to 134, wherein in less than 5%, preferablyin less than about 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the asparagine (N) at position 58 of SEQ ID NO: 9 is deamidated andXI in SEQ ID NO: 39 is deamidated asparagine, respectively.

136. The composition of any one of claims 121 to 135, wherein in less than about 9%,preferably in less than about 8%, preferably in about 6% to 9% of the antibodies, the asparagine (N) at position 318 of SEQ ID NO: 9 is deamidated and X3 in SEQ ID NO:39 is deamidated asparagine, respectively.

137. The composition of any one of claims 121 to 136, wherein in less than about 5%,preferably in less than about 3%, preferably in about 1% to 4% of the antibodies, the asparagine (N) at position 387 of SEQ ID NO: 9 is deamidated and wherein X4 in SEQ ID NO: 39 is deamidated asparagine, respectively.

138. The composition of any one of claims 121 to 137, wherein in one or more of theantibodies, the methionine at position 71, at position 115, at position 255, at position361, and / or at position 431 of SEQ ID NO: 9 is oxidized and XII, XIII, X2, XVI and / or XVIIin SEQ ID NO: 39 is oxidized methionine, respectively.

139. The composition of any one of claims 121 to 138, wherein in less than about 5%,preferably in less than about 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the methionine (M) at position M71 of SEQ ID NO: 9 is oxidized and XII in SEQ ID NO: 39 is oxidized methionine, respectively.

140. The composition of any one of claims 121 to 139, wherein in less than about 5%,preferably in less than about 3%, preferably in less than about 2%, preferably in about 0% to 2% of the antibodies, the methionine (M) at position M115 of SEQ ID NO: 9 is oxidized and XIIIin SEQ ID NO: 39 is oxidized methionine, respectively.

141. The composition of any one of claims 121 to 140, wherein in less than about 5%,preferably in less than about 3%, preferably in about 1% to 4% of the antibodies, the methionine (M) at position M255 of SEQ ID NO: 9 is oxidized and X2 in SEQ ID NO:39 is oxidized methionine, respectively.

142. The composition of any one of claims 121 to 141, wherein in less than about 5%,preferably in less than about 2%, preferably in less than about 1%, preferably in about 0% to 1% of the antibodies, the methionine (M) at position M361 of SEQ ID NO: 9 isoxidized and XVI in SEQ ID NO: 39 is oxidized methionine, respectively.

143. The composition of any one of claims 121 to 142, wherein in more less about 5%,preferably in less than about 3%, preferably in less than about 2%, preferably in about 0% to2% of the antibodies, the methionine (M) at position M431 of SEQ ID NO: 9 is oxidized and XVIIin SEQ ID NO: 39 is oxidized methionine, respectively.

144. The composition of any one of claims 121 to 143, wherein in one or more of theantibodies, the aspartate (D) at position 283 of SEQ ID NO: 9 is modified to iso- aspartate and XIV in SEQ ID NO: 39 is iso-aspartate, respectively.

145. The composition of any one of claims 121 to 144, wherein in one or more of theantibodies, the proline (P) at position 448 of SEQ ID NO: 9 is amidated and X5 of SEQID NO: 7 or 39 is amidated proline, respectively.

146. The composition of any one of claims 121 to 145, wherein in one or more of theantibodies, the glycine (G) at position 449 of SEQ ID NO: 9 and X5 of SEQ ID NO: 7or 39, respectively is absent.

147. The composition of any one of claims 121 to 146, wherein one or more of the antibodiesare fragmented via clipping between asparagine at position 58 and threonine at position 59 of SEQ ID NO: 9, and SEQ ID NO: 7 or 39, respectively.

148. The composition of any one of claims 121 to 147, wherein in one or more of theantibodies the light chain (LC) is glycated.

149. The composition of any one of claims 121 to 148, wherein in less than about 5%,preferably in less than about 2%, preferably in about 0% to 2% of the antibodies, the LC is glycated.

150. The composition of any one of claims 121 to 149, wherein in one or more of theantibodies the heavy chain (HC) is glycated.

151. The composition of any one of claims 121 to 150, wherein in less than about 6%,preferably in less than about 5%, preferably in about 2% to 5% of the antibodies, the HC is glycated.

152. The composition of any one of claims 121 to 151, wherein the antibodies comprise afirst HC (HC1), a first LC (LC1), a second HC (HC2), and a second LC (LC2).

153. The composition of claim 152, wherein the antibodies comprise one or more of thefollowing disulfide bridges: LC:C23-LC:C88 LC:C134-LC:C194 LC:C214-HC:C223 HC:C22-HC:C97 HC:C147-HC:C203 HC1:229-HC2:229 and HC1:232-HC2:232 HC:C264-HC:C324; and HC:C370-HC:C428, wherein the numbering of the cysteine residues (C) corresponds to their positions in SEQ ID NOs: 8 and 9.

154. The composition of any one of claims 121 to 153, wherein the antibodies(i) have a molecular weight of 147.0 to 147.6 kDa;(ii) have a pI of 8.4 (theoretically) and 9.3 (determined), respectively; and / or (iii) have an extinction coefficient (A0.1%) (mL / (mg * cm)) of 1.39 (theoretically) and1.438 (determined), respectively.

155. The composition of any one of claims 121 to 154, wherein the composition comprisesacidic species of the antibodies, preferably about 25% to 33% acidic antibody species.

156. The composition of any one of claims 121 to 155, wherein the composition comprisesthe following charge variants of the antibodies: Main peak ≥ 63.0% Acidic peaks ≤ 32.0% Basic peaks ≤ 5.0%.

157. The composition of any one of claims 121 to 156, wherein the antibodies arerecombinant antibodies produced in Chinese hamster ovary (CHO) cells, preferably inCHO-K1 cells.

158. The composition of claim 157, wherein the method comprises cultivation of the CHO-K1 cells with a pH dead band of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15, preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably of 0.05 or 0.1, most preferably of 0.05.

159. The composition of any one of claims 121 to 158, wherein the HC of the antibodiesfurther comprises a signal peptide, which is derived from a human immunoglobulin heavy chain, and wherein the LC further comprises a signal peptide which is derived from a human immunoglobulin kappa light chain, preferably wherein the signal peptide of the HC has the amino acid sequence set forth in SEQ ID NO: 17, and the signal peptide of the LC has the amino acid sequence set forth in SEQ ID NO: 18.

160. The composition of claim 159, wherein the HC including the signal peptide has theamino acid set forth in SEQ ID NO: 19 and wherein the LC including the signal peptide has the amino acid sequence set forth in SEQ ID NO: 20.

161. The composition of any one of claims 1 to 41 and 121 to 160, which is a stableformulation comprising the antibodies at a concentration of about 25 mg / ml to about 150 mg / ml; histidine at a concentration of about 20 mM; sucrose at a concentration of about 50 mg / ml to about 80 mg / ml;polysorbate 80 (PS) at a concentration of about 0.01% (w / v) to about 0.5% (w / v); water for injection, wherein the formulation has a pH of about 5.3 to about 6.3.

162. The composition of any one of claims 1 to 41 and 121 to 161, which is a pharmaceuticalcomposition comprising the antibodies in an aqueous formulation at a concentration of about 50 mg / ml to about 100 mg / ml for use in a method of treating TTR amyloidosis(ATTR) in a subject, wherein the formulation comprises as excipients L-Histidine, L-Histidine monohydrochloride, sucrose, polysorbate 80 (PS80), and water for injection.

163. The composition of claim 161, or the composition for use according to claim 162,wherein the pH of the formulation is about 5.8164. The composition of claim 161 or 163, or the composition for use according to claim 162or 163, wherein the formulation has as an osmolality of ≥ 240 mOsm / Kg.

165. The composition of claim 161, 163, or 164, or the composition for use according to anyone of claims 162 to 164, wherein the formulation has a shelf-life of 24 months at 2-8°Cand protected from light.

166. The composition of any one of claims 161, and 163 to 165, or the composition for useaccording to any one of claims 162 to 165, wherein the formulation comprises theantibody at a concentration of about 50 mg / ml or about 100 mg / ml and histidine at a concentration of about 20 mM, sucrose at a concentration of about 6.5% weight pervolume (w / v) or about 8% (w / v) sucrose, and PS80 at a concentration of about 0.03% w / v, wherein the formulation has a pH of about 5.8.

167. The composition of any one of claims 161, and 163 to 166, or the composition for useaccording to any one of claims 162 to 166, wherein the formulation, when added up to about 2 ml essentially consists of:50 mg or 100 mg of the antibody, 2.12 mg L-Histidine, 5.56 mg L-Histidine monohydrochloride 160 mg sucrose, 0.6 mg PS80, and water for injection.

168. The composition of any one of claims 161, and 163 to 167, or the composition for useaccording to any one of claims 162 to 167, wherein the antibodies are produced in the Chinese Hamster Ovary (CHO) cells, preferably in the CHO cell line K1.

169. The composition of any one of claims 161, and 163 to 168, or the composition for useaccording to any one of claims 162 to 168, wherein the formulation is suitable for intravenous administration.

170. The composition of any one of claims 161, and 163 to 169, or the composition for useaccording to any one of claims 162 to 169, wherein the formulation is provided in a 2- mL or 20-mL single dose vial.

171. The composition of any one of claims 161, and 163 to 170, or the composition for useaccording to any one of claims 162 to 170, wherein the formulation is supplied in a 2mL glass vial with an aluminum flip-off seal over a rubber stopper.

172. The composition of any one of claims 161, and 163 to 171, or the composition for useaccording to any one of claims 162 to 171, wherein the formulation is a preservative- free concentrate for solution for infusion that is presented as sterile, colorless to slightly yellow, clear to slightly opalescent liquid, essentially free of visible particles.

173. The composition for use according to any one of claims 162 to 172, wherein theformulation is diluted in sterile glucose before administration, as an intravenous infusion.

174. A pharmaceutical container comprising the composition of any one of claims 161, and163 to 172.

175. The pharmaceutical container of claim 174, which is a 2 ml or 20 ml vial.

176. The vial of claim 175 which is a glass vial with an aluminum flip-off cap over a 13 mmrubber stopper.

177. The vial of claim 175 to 176, which contains an approximate 12.5% volume overfill, ora total volume of 2.25 ml or 22.5 ml of the pharmaceutical formulation.

178. A stable aqueous formulation for use in a method of treating TTR amyloidcardiomyopathy (ATTR-CM), wherein the formulation (i) essentially consists of:(a) an anti-TTR antibody comprising an immunoglobulin heavy chain (HC)comprising the amino acid sequence of SEQ ID NO: 7 or 39 or SEQ ID NO:9 and an immunoglobulin light chain (LC) comprising the amino acid sequence of SEQ ID NO: 8, (b) histidine at a concentration of about 20 mM,(c) sucrose at a concentration of about 8% (w / v),(d) PS80 at a concentration of about 0.03% w / v,(e) water for injections,(ii) has a pH of about 5.8;(iii) is contained in a 2 mL single use vial comprising about 100 mg of antibody or ina 20 mL single use vial comprising 1000 mg of antibody: (iv) is diluted prior to administration with a sterile glucose solution to a concentrationof not below 1 mg / mL antibody; and (v) is administered by intravenous infusion.

179. The formulation for use according to claim 178, wherein the N-terminal glutamine ofthe HC amino acid sequence is converted to pyroglutamate, the C-terminal lysine of the HC amino acid sequence is deleted, and wherein the HC is N-glycosylated.

180. The formulation for use according to claim 179, wherein the HC has the amino acidsequence of SEQ ID NO: 15.

181. A therapeutic kit comprising(i) one or more container(s) of claim 174 to 177;(ii) means for delivering the formulation to a human subject, particularly whereinthe means comprise an infusion bag or a syringe for intravenous administration of the antibody.

182. The therapeutic kit of claim 181, wherein the formulation is a preservative-free, clear toopalescent and colorless to pale yellow solution, provided as 100 mg / 2 mL in a vial.

183. An article of manufacture comprising(i) one or more container(s) of any one of claims 174 to 177, and(ii) a label, wherein the label prescribes that the antibody is indicated for thetreatment of ATTR, especially wild-type or hereditary transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) and / or (iii) a leaflet prescribing that the antibody is to be administered intravenously.

184. The article of manufacture of claim 183, wherein the container comprises a 2mL or 20mL glass vial.

185. The article of manufacture of claim 183 or 184, wherein the antibody in the container isdiluted prior to administration, wherein the dilution is performed with a 5% glucose solution, optionally wherein a glucose solution for dilution is provided in a second container in the article.

186. The article of manufacture of any one of claims 183 to 185, wherein the formulation ofthe antibody is a preservative-free, clear to opalescent and colorless to pale yellow solution, provided as 100 mg / 2 mL in a vial.

187. A method of treating TTR amyloidosis (ATTR), preferably ATTR cardiomyopathy(ATTR-CM) and / or ATTR polyneuropathy (ATTR-PN), comprising administering to a patient in need thereof, the antibody of any one of claims 42 to 105 and 119, or the composition of any one of claims to 1 to 41, 121 to 161, and 163 to 171.

188. The method of claim 187, wherein the method comprises administering the antibody toa patient with ATTR-CM, thereby treating the ATTR-CM in said patient.

189. The method of claim 187, wherein the method comprises administering the antibody toa patient with ATTR-PN, thereby treating the ATTR-PN in said patient.

190. The method of any one of claims 187 to 189, wherein the antibody is diluted andadministered as an intravenous infusion,191. The method of claim 190, wherein dilution is performed in a 5% glucose solution.

192. The method of any one of claims 187 to 191 wherein the patient has been previouslytreated with and / or is concurrently receiving a TTR tetramer stabilizer.

193. The method of claim 192, wherein the TTR tetramer stabilizer is selected fromtafamidis, and acoramidis.

194. Use of the antibody of any one of claims 42 to 105 and 119, or the composition of anyone of claims 1 to 41, 121 to 161, and 163 to 171 for the manufacture of a medicamentfor the treatment of TTR amyloidosis (ATTR).

195. The antibody of any of claims 42 to 105 and 119, wherein the antibody is made in CHOcells, preferably CHO-K1 cells, and is designated ALXN2220.

196. The composition for use according to any one of claims 162 to 173, wherein the subjecthas been treated or is concurrently treated with a TTR tetramer stabilizer, preferably with tafamidis or acoramidis,197. A method of producing an antibody or antigen-binding fragment thereof of any one ofclaims 42 to 105 and 109, comprising a) cloning the nucleic acid molecule of any one of claims 107 to 110 and 112 whichcomprises the first nucleotide sequence into an expression vector and cloning the nucleic acid molecule of any one of claims 107 to 110 and 112 which comprisesthe second nucleotide sequence into an expression vector, wherein the first and the second nucleotide sequences may be provided in the same or different expression vectors;b) transforming the expression vector(s) into a non-human host cell, preferably into a CHO cells, more preferably CHO-K1 cells; c) culturing the host cell under conditions allowing for the expression of the immunoglobulin chains comprising heavy chain and light chain; d) isolating the immunoglobulin chains and resultant IgG antibody, respectively, from the culture and optionally digesting the IgG antibody to generate antigen- binding fragments of the antibody, e.g., using enzymatic digestion comprising papain cleavage to generate Fab fragments, and optionally e) formulating the antibody in an aqueous solution comprising the antibody at aconcentration of about 50 mg / ml or about 100 mg / ml and histidine at a concentration of about 20 mM, sucrose at a concentration of about 6.5% weight per volume (w / v) or about 8% (w / v) sucrose, and PS80 at a concentration of about 0.03% w / v, wherein the formulation has a pH of about 5.8 to generate a pharmaceutical composition comprising the antibody; andf) optionally filing the composition into a vial, andg) further optionally packing the pharmaceutical composition and vial,respectively, in a kit together with instructions for administration of the antibody, e.g., intravenously in a human patient.

198. The method of claim 197, wherein step (c) comprises cultivation of the cells with a pHdead band of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15, preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably of 0.05 or 0.1, most preferably of 0.05.

199. A method of producing the antibody composition of any one of claims 1 to 42 and 121to 173, the method comprising a) cloning the nucleic acid molecule of any one of claims 107 to 110 and 112 which comprises the first nucleotide sequence into an expression vector and cloning the nucleic acid molecule of any one of claims 107 to 110 and 112 which comprises the second nucleotide sequence into an expression vector, wherein the first and the second nucleotide sequences may be provided in the same or different expression vectors; b) transforming the expression vector(s) into CHO-K1 cells;c) culturing CHO-K1 cells under conditions allowing for the expression of theimmunoglobulin chains comprising heavy chain and light chain, wherein cultivation is performed with a pH dead band of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15, preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably of 0.05 or 0.1, most preferably of 0.05; d) isolating the immunoglobulin chains and resultant IgG antibody, respectively, from the culture to prepare the composition and optionally digesting the IgGantibody to generate antigen-binding fragments of the antibody, e.g., using enzymatic digestion comprising papain cleavage to generate Fab fragments; and optionally e) formulating the antibody in an aqueous solution comprising the antibody at aconcentration of about 50 mg / ml or about 100 mg / ml and histidine at a concentration of about 20 mM, sucrose at a concentration of about 6.5% weight per volume (w / v) or about 8% (w / v) sucrose, and PS80 at a concentration of about 0.03% w / v, wherein the formulation has a pH of about 5.8 to generate a pharmaceutical composition comprising the antibody; and f) optionally filing the composition into a vial, andg) further optionally packing the pharmaceutical composition and vial,respectively, in a kit together with instructions for administration of the antibody, e.g., intravenously in a human patient.

200. A method of manufacturing of the antibody of any one of claims 42 to 105 and 120, orthe composition of any one of claims 1 to 42, and 121 to 173 (a) culturing the cell of any one of claims 114 to 116, wherein cultivation is performed with a pH dead band of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15, preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably of 0.05 or 0.1, most preferably of 0.05; and (b) isolating the antibody or immunoglobulin chain(s) thereof from the culture.

201. A method of validating an amyloid depleting drug comprising(i) incubating tissue sections having amyloid deposits with macrophages,preferably THP-1 derived macrophages, in the presence of the amyloid depleting drug,wherein the tissue sections are stained with an amyloid specific fluorescent dye and / or the amyloid depleting drug is labeled with a fluorescent dye; and (ii) performing high-resolution live-cell imaging,wherein (a) an overlap of the fluorescence signal of the amyloid depleting drug and theamyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocyticvesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from thefluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation.

202. The method of claim 201, wherein items (a) to (c) are not observed for a control sample,wherein the tissue sections having amyloid deposits and macrophages have not been incubated in the presence of the amyloid depleting drug, but optionally in the presence of a control compound which does not bind amyloid and / or is not capable of mediating phagocytosis.

203. The method of claim 201 or 202, wherein the amyloid depleting drug or apharmaceutical composition comprising the amyloid depleting drug is used for the treatment of an amyloidosis or amyloid-related disease.

204. A screening method of identifying and optionally obtaining an amyloid depleting drugfrom a plurality of test compounds comprising (i) incubating tissue sections having amyloid deposits with macrophages,preferably THP-1 derived macrophages, in the presence of the test compound, wherein the tissue sections are stained with an amyloid specific fluorescent dye and / or the test compound is labeled with a fluorescent dye; and (ii) performing high-resolution live-cell imaging,wherein (a) an overlap of the fluorescence signal of the test compound and the amyloidfluorescence signal indicates binding of the test compound to the amyloid;(b) the presence of a punctuate and intracellular fluorescence signal in phagocyticvesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from thefluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation, wherein the presence of any one of items (a) to (c) indicates the suitability of the test compound as amyloid depleting drug, and optionally using the amyloid depleting drug or a pharmaceutical composition comprising the amyloid depleting drug for the treatment of an amyloidosis or amyloid-related disease.

205. A method of analyzing the impact of an agent on the amyloid depleting activity of theamyloid depleting drug comprising (i) incubating a sample of tissue sections having amyloid deposits with macrophages,preferably THP-1 derived macrophages, in the presence of the amyloid depleting drug and the agent; and iii) performing high-resolution live-cell imaging of each sample,wherein (a) an overlap of the fluorescence signal of the amyloid depleting drug and theamyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocyticvesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from thefluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation, wherein, compared to a control sample, wherein the tissue sections having amyloid deposits and macrophages have been incubated in the presence of the amyloid depleting drug but without the agent a substantially unaltered fluorescence pattern of items (a) to (c) is indicative for the suitability of the combination of the amyloid depleting drug and the agent in the treatment of an amyloidosis or amyloid-related disease and an substantially altered fluorescence pattern of any one of items (a) to (c) indicates an impact of the agent on the amyloid depleting activity of the amyloid depleting drug, optionally wherein (a) an enhanced fluorescence signal;(b) an enhanced intracellular fluorescence signal in the phagocytic vesicles; and(c) an enhanced separation of the punctuate fluorescence signal from thefluorescence signal of the amyloid, indicates a synergistic effect on the amyloid depleting activity of the amyloid depleting drug and (a) a reduced fluorescence signal;(b) a reduced intracellular fluorescence signal in the phagocytic vesicles; and(c) a reduced separation of the punctuate fluorescence signal from the fluorescencesignal of the amyloid, indicates a detrimental effect on the amyloid depleting activity of the amyloid depleting drug.

206. A method of screening an amyloid depleting drug for its capability to bind to amyloid,and to mediate macrophage recruitment to amyloid deposits, followed by amyloid fragmentation and internalization by a method comprising (i) incubating tissue sections having amyloid deposits with macrophages,preferably THP-1 derived macrophages, in the presence of the amyloid depleting drug, wherein the tissue sections are stained with an amyloid specific fluorescent dye and / or the amyloid depleting drug is labeled with a fluorescent dye; and (ii) performing high-resolution live-cell imaging,wherein (a) an overlap of the fluorescence signal of the amyloid depleting drug and theamyloid fluorescence signal indicates binding of the amyloid depleting drug to the amyloid; (b) the presence of a punctuate and intracellular fluorescence signal in phagocyticvesicles indicates macrophage mediated internalization of amyloid; and (c) the successively separation of a punctuate fluorescence signal from thefluorescence signal of the amyloid indicates macrophage mediated amyloid fragmentation, and optionally using the amyloid depleting drug or a pharmaceutical composition comprising the amyloid depleting drug for the treatment of an amyloidosis or amyloid- related disease.

207. The method of any one of claims 201 to 206, wherein the high-resolution live-cellimaging uses refractive index imaging for cell visualization and fluorescence microscopy for amyloid imaging.

208. The method of any one of claims 201 to 207, wherein the amyloid depleting drug islabeled with a fluorescent dye which is different from the fluorescent dye used to stain the amyloid deposits.

209. The method of any one of claims 201 to 208, wherein the tissue sections are obtainedfrom a patient suffering from an amyloidosis or amyloid-related disease.

210. The method of any one of claims 205 to 209, wherein the amyloidosis or the amyloid-related disease is transthyretin (TTR) amyloidosis or a TTR amyloid-related disease, preferably cardiac TTR amyloidosis.

211. The method of any one of claims 201 to 210, wherein the amyloid depleting drug is ananti-amyloid antibody or comprises an anti-amyloid antibody fragment.

212. The method of any one of claims 201 to 211, wherein the amyloid depleting drug is ananti-TTR antibody or comprises an anti-TTR antibody fragment and / or the control compound is an isotype control antibody.

213. The method of claim 210 or 212, wherein the antibody is a human-derived, preferablyhuman memory B cell-derived antibody or a variant thereof comprising a heterologous constant domain, or a humanized antibody, or chimeric antibody, preferably wherein the antibody is an IgG1 antibody, such as an IgG1, λ antibody or an IgG1, κ antibody.

214. The method of any one of claims 205 to 213, wherein the agent is a second drug for thetreatment of an amyloidosis, or a painkiller, preferably wherein the second drug is a TTR tetramer stabilizer or silencer.

215. A method of producing a pharmaceutical composition of an amyloid depleting drugcomprising (i) providing, optionally producing the amyloid depleting drug;(ii) subjecting the amyloid depleting drug to the method of any one of claims 201 to202 and 205 to 214;(iii) using the information obtained in step (ii) as part of an assessment of whetherthe amyloid depleting drug may be used as a pharmaceutical composition or not; and optionally (iv) formulating the amyloid depleting drug found to be useful as a pharmaceuticalcomposition in step (iii) with a pharmaceutically acceptable carrier, preferably comprising a buffer, a tonicity agent and / or a surfactant, most preferably all three components and optionally (v) using the pharmaceutical composition for the treatment of an amyloidosis oramyloid-related disease.

216. A method for characterization, validation, development and / or quality control of anamyloid depleting drug comprising (i) providing, optionally producing the amyloid depleting drug;(ii) subjecting the amyloid depleting drug to the method of any one of claims 201 to202 and 207 to 214;(iii) communicating the information obtained in (ii) to a client, contracting party orcooperation partner and / or selecting the drug that has been determined to be a suitable amyloid depleting drug; and optionally (iv) using the amyloid depleting drug or a pharmaceutical composition comprisingthe amyloid depleting drug for the treatment of an amyloidosis or amyloid- related disease.

217. A kit useful for performing the method of any one of claims 201 to 216, comprising afirst fluorescent dye for amyloid staining and / or a second fluorescent dye for labelling of the amyloid depleting drug, preferably a negative and / or positive control, and optionally with instructions for use, preferably wherein the positive control is the antibody of any one of claims 42 to 105, and 120.

218. The method of any one of claims 201 to 214, wherein the method is performed inaddition to a method using a patient-derived amyloid xenograft (PDAX) non-humananimal model, wherein the animal is characterized by an implant of amyloid fibrils derived from the tissue or organ of a patient suffering from an amyloidosis or amyloid-related disease, wherein the amyloid and amyloid fibrils, respectively, comprise amyloid transthyretin (ATTR), and wherein the amyloid fibrils are subcutaneously or subcapsularly implanted or implanted in the kidney, the peritoneum, the muscles, the brain, the ventricles, the nerves, the eyes, the tongue, or the heart,wherein the method comprises (a) administering the amyloid depleting drug or a test substance to the PDAX non-human animal model; and (b) determining amyloid fibrils in the model,wherein the accelerated elimination or reduction of the amyloid fibrils upon administration of the drug or the test substance compared to a control is indicative for the suitability of the amyloid depleting drug for the treatment of an amyloidosis or amyloid-related disease and for the amyloid depleting activity of the test substance, respectively.

219. The method of any one of claims 201 to 216 and 218, wherein the amyloid depletingdrug is the antibody of any one of claims 42 to 105 and 120.

220. A method for the production of an antibody comprising an immunoglobulin heavy chain(HC) having the amino acid sequence of SEQ ID NO: 9 and an immunoglobulin light chain (LC) having the amino acid sequence of SEQ ID NO: 8, comprising, (a) culturing a host Chinese Hamster Ovary K1 (CHO-K1) cell comprising one or more expression vectors or vector systems comprising the polynucleotides encoding the antibody HC and the LC, under conditions sufficient for the expression of the antibody in the culture; (b) setting a pH setpoint and pH dead band of the culture to adjust level of acidic, basic, and / or neutral antibody species in the culture; and (c) isolating the antibody HC and LCfrom the cell culture; and (d) optionally formulating the isolated antibody into a pharmaceutical formulation.

221. The method of claim 220, wherein step (b) comprises setting a pH setpoint of about 6.90 and a pH deadband of less than 0.2, preferably of ≤ 0.175, preferably of ≤ 0.15,preferably of ≤ 0.125, preferably of ≤ 0.1, preferably of ≤ 0.075, preferably of ≤ 0.05, more preferably between 0.05 to 0.1 to reduce level of acidic antibody species; preferably setting a pH deadband of about 0.05.

222. The method of claim 221, wherein implementation of step (b) reduces the level of acidic species in cultured antibody preparation compared to control, e.g., an antibody preparation produced using an identical production method except step (b) is implemented at pH 6.90 and pH deadband of about 0.

20.

223. The method of claim 221 or 222, wherein implementation of step (b) reduces levels of N-linked mannose-5 glycan (Man5); preferably wherein the reduction in Man5 levels is greater than >20%; more preferably wherein the reduction in Man5 levels is about 40%- 50% compared to control, e.g., an antibody preparation produced using an identical production method except step (b) is implemented at pH 6.90 and pH deadband of about 0.20.

224. The method of any one of claims 220 to 223, wherein step (b) is implemented in theproduction phase comprising day 5 to day 14 of the culture process, e.g., between day 5 to day 14 post-seeding of the host cells, e.g., CHO-K1 cells.

225. The method of any one of claims 220 to 224, wherein step (b) controls high mannosespecies in the antibody preparation, without concomitantly and adversely impacting secondary quality attributes selected from (1) relative levels (in %) of main vs. high molecular weight (HMW) vs. low molecular weight (LMW) antibody species in the preparation, e.g., as determined by size exclusion chromatography (SEC); (2) relative levels (in %) of main antibody species in the preparation, e.g., as determined using capillary electrophoresis sodium dodecyl sulfate under non-reduced conditions (CE- SDS-NR); and / or (3) relative levels (in %) of antibody heavy and light chains in the preparation, e.g., as determined using capillary electrophoresis sodium dodecyl sulfate under reduced conditions (CE-SDS R).

226. An antibody produced using any one of the production methods of claims 220 to 225.

227. The antibody of claim 226, wherein the antibody comprises heavy and light chains ofALXN2220 / NI006.