25 results about "Paratope" patented technology

A major challenge in the field of antibody-based therapeutics is the development of antibodies that have longer duration of action, longer half-life and can be delivered to a patient at lower doses. The current methods to achieve this aim depend on the engineering modification of the pH-dependent antigen binding properties of the antibodies, which is very strenuous and generally requires further optimization of the pH-sensitive interactions in a low-throughput, individualized manner because these methods depend mainly on the introduction of histidine mutations in specific antibody complementarity determining regions (CDRs). In the present invention, the inventors provide antibodies and other antigen-binding proteins that carry mutations outside of the complementals, thereby conferring universal pH-sensitive binding properties to the antibodies. The invention also relates to methods of isolating and generating said antigen binding proteins, compositions and medical uses thereof.

The present application relates to antigen binding molecules comprising a pair of biparatomotic target binding domains, a pair of cytokine receptor binding domains and an Fc domain wherein the target binding domains concurrently bind to a target antigen and the cytokine receptor binding domains bind to a subunit of a cytokine receptor complex. Biparatopic assembly of the cytokine receptor binding domain in the presence of the target antigen allows for selective activation of cytokine receptors and efficient mimicking of cytokine activity in a targeted manner.

Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

Predictive models are deployed to generate epitope predictions (e.g., B-cell epitopes). Predictive models analyze structural features of a protein, such as an antibody, or an antibody-antigen pair, and can identify epitopes and paratopes.

Described and featured herein are biparatopic antibodies that specifically bind Fms Related Receptor Tyrosine Kinase 3 (FLT-3), antibody drug conjugates (ADC's) comprising such antibodies, as well as methods of using such antibodies and ADC for the treatment of diseases, such as cancer. Particularly effective are biparatopic antibodies in which one binding arm binds to an epitope of FLT3 that is located N-terminal of the D1 domain and the other binding arm binds to an epitope located on or includes a portion of domain D3.

The present invention relates to an anti-mGLUR2 biparatopic nanobody including (i) one single domain antibody having specific CDRs; preferably a CDR1 having a sequence set forth as SEQ ID NO:1, a CDR2 having a sequence set forth as SEQ ID NO:2 and a CDR3 having a sequence set forth as SEQ ID NO:3; and (ii) another single domain antibody having specific CDRs.

The application relates to cytokine receptor agonists comprising: i) a first PD-1 binding domain capable of binding a first epitope on PD-1, ii) a second PD-1 binding domain capable of binding a second epitope on PD-1, iii) an IL2Rγ binding domain, iv) an IL2Rβ binding domain, and v) an Fc region, and wherein the first and second PD-1 binding domains do not compete for binding on PD-1. The PD1-binding domains simultaneously bind the PD-1 and the IL-2 receptor-binding domains bind subunits of an IL-2 receptor complex. Biparatopic assembly of the IL-2 receptor-binding domains in the presence of PD-1 allows to selectively activate IL-2 receptors and effectively mimic cytokine activity in a targeted manner.

Provided herein are tetravalent antibodies and immunoconjugates, wherein the antibodies are conjugated to a payload. The antibodies can comprise a number of different architectures, with the paratopes formed, e.g., as Fabs or diabodies, positioned relative to one another and to the Fc region. Also provided are methods of making and using the above antibodies and immunoconjugates.

A method for selecting camelid nanobodies from an array library collected from B cells of a camelid animal immunized with an antigen is provided. The method comprises (a) (i)phenylalanine (F) at position 42 (IMGT number), and (ii)a short hinge, and (iii)two or more cysteines in the nanobody sequence, and (iv)glutamine (Q) at position 123 (IMGT number), and (v)a low immunogenicity index, and (vi)a non-conventional VHH derived from germline IGHV3, or valine (V) included at position 42 (IMGT number), and (vii)a non-conventional VHH derived from germline IGHV4, or isoleucine (I) included at position 42 (IMGT number), and (viii)histidine (H), aspartic acid (D), or glutamic acid (E) in the CDR region, and (ix)histidine (H), aspartic acid (D), or glutamic acid (E) in the top 3 amino acid residues of the nanobody sequence, the FR2 region, or the top 16 amino acid residues of the FR3 region, and (x)tyrosine (Y) at position 42 (IMGT number), and a nanobody having a cyclic concave paratope structure arrangement, or (xi)phenylalanine (F) at position 42 (IMGT number), and a nanobody having a convex paratope structure arrangement, identifying a camelid nanobody having at least one of the features, and (b)measuring one or more biological activities of the nanobody identified in step (a).

The present disclosure provides monoclonal and recombinant anti-CDH17 antibodies (including CDH17 biparatopic and CDH17xCD3 bispecific antibodies and CDH17-binding fragments. Such antibodies and binding fragments are useful for the treatment of cancer, cither alone or in combination with other agents.

The present application relates to a pair of antigen binding molecules, each molecule comprising a target binding domain, a cytokine receptor binding domain and an Fc domain wherein the target binding domain concurrently binds to a target antigen and the cytokine receptor binding domain binds to a subunit of a cytokine receptor complex. Biparatome assembly of the cytokine receptor binding domain in the presence of the target antigen allows for selective activation of cytokine receptors and efficient mimicking of cytokine activity in a targeted manner.

Characterization of the binding dynamics at the interface between any two proteins that specifically interact plays a role in myriad biomedical applications. The methods disclosed herein provide for the high-throughput characterization of the specific interaction at the interface between two protein binding partners and the identification of functionally significant mutations of one or both protein binding partners. For example, the methods disclosed herein may be useful for epitope and paratope mapping of an antibody-antigen pair, which is useful for the discovery and development of novel therapies, vaccines, diagnostics, among other biomedical applications.

This invention specifically provides antibodies or antigen-binding fragments thereof that are specific to CD45. The antibodies include monospecific antibodies to CD45 and antibodies with dual complementary sites to CD45. The antibodies are typically capable of binding to both human and cynomolgus monkey CD45. The antibodies of this invention have various uses, including targeting, exhausting, and killing cells expressing CD45, particularly for the treatment of cancers or autoimmune diseases mediated by CD45-positive cells, or prior to cell transplantation.

Provided herein are, inter alia, antibodies (e.g., humanized antibodies, chimeric antibodies, monoclonal antibodies, biparatopic antibodies, antibody fragments (e.g., Fab')), which bind CD38 with high efficiency and specificity. Inter alia, are provided biparatopic antibodies that bind CD38 specifically and effectively. The biparatopic antibodies provided herein may have an increased binding avidity relative to the monoclonal antibodies they are derived from and are specifically useful for therapeutic and diagnostic purposes.

Provided is a method of selecting a camelid nanobody from a library of camelid nanobody sequences collected from B cells from a camelid immunized with an antigen. The method comprises: (a) identifying a camelid nanobody that has at least one of the following features (i) a phenylalanine (F) at position 42 (IMGT numbering); (ii) a short hinge; (iii) two or more cysteines in the nanobody sequence; (iv) a glutamine (Q) at position 123 (IMGT numbering); (v) low immunogenicity metric; (vi) non-classic VHH derived from germline IGHV3 or a valine (V) at position 42 (IMGT numbering); (vii) non-classic VHH derived from germline IGHV4 or an isoleucine (I) at position 42 (IMGT numbering); (viii) a histidine (H), aspartic acid (D) or glutamic acid (E) in the CDR region; (ix) a histidine (H), aspartic acid (D) or glutamic acid (E) in the first three amino acid residues, the FR2 region, or the first sixteen amino acid residues of the FR3 region of the nanobody sequence; (x) a tyrosine (Y) at position 42 (IMGT numbering), and the nanobody having a loop, concave paratope structure configuration; or (xi) a phenylalanine (F) at position 42 (IMGT numbering), and the nanobody having a convex paratope structure configuration; and (b) measuring one or more biological activities of the nanobody identified in step (a).

Provided herein are anti-PD-L1 multiparatopic antibody constructs that include a plurality of antigen-binding fragments, wherein a first antigen-binding fragment of the plurality of antigen-binding fragments binds specifically to a first PD-L1 epitope, and wherein a second antigen-binding fragment of the plurality of antigen-binding fragments binds specifically to a second PD-L1 epitope.

Workflows for the efficient identification of viral epitopes and / or host paratopes are provided. The workflows leverage artificial intelligence to quickly and reliably identify candidate epitopes for immunogen development thereby reducing the lead time of vaccine development. Immunogenic compositions for use in the treatment and / or prevention of porcine reproductive and respiratory syndrome virus (PRRSV) and Infectious Bronchitis Virus (IBV) are also provided, as are antibodies or antigen binding fragments.

The present disclosure provides monoclonal and recombinant anti-CDH17 antibodies (including CDH17 biparatopic and CDH17xCD3 bispecific antibodies and CDH17-binding fragments. Such antibodies and binding fragments are useful for the treatment of cancer, either alone or in combination with other agents.

The present disclosure provides anti-5T4 antigen binding domains that can be incorporated into antibodies and recipients, including bispecific anti-5T4 antibodies, biparatopic anti-5T4 antibodies, and antibody-drug conjugates thereof, the antibody-drug conjugates comprising: a first antigen binding domain that specifically binds to a first 5T4 epitope; a second antibody antigen binding domain that specifically binds to a second 5T4 epitope different from the first 5T4 epitope; wherein the first antigen binding domain is operably linked to the second antigen binding domain; and a chemotherapeutic agent. The disclosure further provides methods of using the same for treating cancer.

The application relates to antigen binding molecules comprising a pair of biparatopic target-binding domains, a pair of cytokine receptor-binding domains and an Fc domain, wherein the target-binding domains simultaneously bind the target antigen and the cytokine receptor-binding domains bind subunits of a cytokine receptor complex. Biparatopic assembly of the cytokine receptor-binding domains in presence of the target antigen allows to selectively activate cytokine receptors and effectively mimic cytokine activity in a targeted manner.

The present invention relates to biparatopic antigen-binding molecules, such as biparatopic antibodies or functional fragments thereof, and mixtures comprising at least two monospecific antibodies or functional fragments thereof, that can be employed for the prevention, alleviation, treatment and / or diagnosis of diseases, disorders and abnormalities associated with CNS proteins such as alpha-synuclein (α-synuclein, A-synuclein, aSynuclein, A-syn, α-syn, aSyn, a-syn), Tau, TDP-43, ASC, NLRP3, C5a, C1q, C3, huntingtin or prion protein. The present invention further relates to the use of the molecules of the invention for determining a pre-disposition to a disorder, disease or abnormality, monitoring residual disorder, disease or abnormality associated with CNS proteins such as alpha-synuclein (α-synuclein, A-synuclein, aSynuclein, A-syn, α-syn, aSyn, a-syn), Tau, TDP-43, ASC, NLRP3, C5a, C1q, C3, huntingtin or prion protein, or predicting the responsiveness of a patient who is suffering from such a disorder, disease or abnormality to the treatment with a certain medicament.

The present invention relates to T-cell adapter masking molecules and methods related thereto that reduce the severity of cytokine release syndrome, wherein the molecules have (i.) binding peptides that bind to the T-cell-engaging complementals of bispecific T-cell adapter molecules (TCEs), (ii.) linkers, and (iii.) half-life prolonging polymers.

Provided herein are antibodies and antibody fragments that bind to human TNFRSF25. The antibodies may be monoclonal and / or biparatopic antibodies and / or single-chain fragment variable (scFv) antibodies. Methods of treating or preventing diseases or disorders associated with inflammation and / or autoimmunity are provided, comprising administering to a patient in need thereof an effective amount of a human TNFRSF25-binding antibody.

The present invention relates to T cell engager masking molecules, and methods related thereto, that contribute to reduce the severity of cytokine release syndrome, wherein said molecules comprise (i.) a binding peptide which is deprived of an isomerization site and which binds to a T-cell engaging paratope of a bispecific T cell engager molecule (TCE), (ii.) a linker, and (iii.) a half-life extending polymer.

This disclosure provides an antibody design method based on flow matching and graph neural networks. The method comprises the following steps: Step 1, input parsing and initial antibody structure construction; Step 2, antigen epitope surface modeling; Step 3, local generation of binding regions based on flow matching; Step 4, global propagation of a surface-enhanced message encoder; Step 5, sequence-structure joint convergence generation, ultimately outputting a full-atom 3D antibody structure and paratope residue sequences. The above process achieves more accurate interface modeling and structure generation by constructing a flow matching generation process in the binding region and utilizing a global geometric message passing mechanism driven by antigen surface point clouds; simultaneously, by restricting flow matching computation to local regions, the computational overhead of generating large molecular structures is effectively reduced.