Parvovirus antibody formulations and methods for veterinary use

Abstract

Provided are various embodiments relating to formulations parvovirus therapy and / or prevention, and methods of using the same, for example, for providing passive immunity against infection with a canine or feline parvovirus and / or treating parvoviral infection in companion animals, such as dogs and cats. Formulations may comprise parvovirus antibodies, including caninized, felinized, and chimeric antibodies, that bind to canine and / or feline parvovirus, for example, having improved expression characteristics. In various embodiments, the parvovirus antibodies have ADCC, ADCP, and / or CDC effector functions. In various embodiments, such formulations can be used in methods to prevent and / or treat parvoviral infection in subjects, such as dogs and cats. For example, the formulations provided may be used to provide passive immunity against infection with a canine or feline parvovirus.

Description

Attorney Reference No. 2920951-538977PARVOVIRUS ANTIBODY FORMULATIONS AND METHODS FOR VETERINARY USE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U. S. Provisional Application No. 63 / 748,717, filed January 23, 2025, the content of which is hereby incorporated by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] A Sequence Listing in XML format, submitted under 37 C. F. R. §§ 1.831-1.835, entitled 2920951 -538977_Sequence_Listing.xml, 101,566 bytes in size, generated on January 22, 2026, and filed via EFS-Web, is provided in lieu of a paper copy. This Sequence Listing is incorporated by reference into the specification for its disclosures.FIELD

[0003] The present disclosure relates to compositions and methods comprising parvovirus antibodies. The disclosure further relates to compositions exhibiting improved stability and neutralizing binding to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV). Compositions described herein further provide for improved shelf-life and stability under a variety of conditions. Compositions described herein further provide for passive immunity against infection with a CPV or FPV and / or treating parvoviral infection in companion animals, such as dogs and cats.BACKGROUND

[0004] Parvoviruses are a family of animal viruses that constitute the family Parvoviridae. Protoparvovirus carnivoran 7 is a species of the family Parvoviridae that infects camivorans. Protoparvovirus carnivoran 1 can be divided into two major groups: the canine parvovirus (CPV) and the feline panleukopenia virus (FPV).

[0005] Canine Parvovirus (CPV) is the most important enteric virus infecting dogs worldwide (see, for example, S. Nandi, Manoj Kumar. Canine Parvovirus: Current Perspective. Indian J. Virol. 2010; 21 (1 ):31 -44). The CPV virion is a non-enveloped, DNA virus. There are multiple variants of the original CPV, including CPV-2a, CPV-2b, and CPV-2c. The variants of CPV-2 differ from one another by only a few amino acids (Carla Miranda,Attorney Reference No. 2920951-538977Gertrude Thompson. Canine parvovirus: the worldwide occurrence of antigenic variants. Journal of General Virology. 2016; 97, 2043-2057). Quite persistent in the environment, CPV may remain infective for months. CPV spreads via direct and indirect contact. Upon contact with the oral mucosa, CPV begins to replicate in local lymphatics and spreads systemically. With a 4 to 14 day incubation period, CPV targets rapidly dividing cells of the body including bone marrow, lymphocytes and intestinal crypt epithelial cells.

[0006] Clinical disease manifests as fever and depression followed by vomiting, diarrhea (profuse and bloody), lymphopenia, dehydration and quite often secondary septicemia and death. Mortality may exceed 70% in puppies (Melissa Kennedy, Adesola Odunayo. Canine Parvovirus. Clinician’s Brief. 2017). Infection is most common in puppies after weaning as the maternal antibodies begin to wane. Vaccines are readily available and effectively protect against all variants of CPV-2.

[0007] Although properly timed vaccinations are protective, parvovirus infection remains a problem. The primary population of susceptible canines includes puppies in the vulnerable window where maternally derived antibody has waned to non-protective levels and before vaccination has been given (see Figure 1). Puppies under 24 weeks of age are at highest risk of CPV disease. Additionally, puppies with failure of passive transfer of maternally derived antibodies is another vulnerable population. Outbreaks continue to occur in naive kennel and shelter populations as well.

[0008] Treatment for CPV infection up to this point has been largely supportive.Treatment typically involves intravenous fluids, antiemetics, and broad-spectrum antibiotics to protect against septicemia. Various other treatments have been tried unsuccessfully including anti-virals and hyperimmune plasma (Brindhalakshmi B, Mukhopadhyay HK, Antony PX, Thanislass J, Vijayalakshmi P, Mangadevi N. Isolation and molecular characterization of canine and feline parvovirus strains - an updated review. Journal of Dairy, Veterinary & Animal Research. 2016; 3(5): 164-169). Hospitalization is typically recommended which can be cost-prohibitive for many owners and can lead to the decision to euthanize. Hospitalizing dogs with CPV infection requires strict isolation protocols. This can prove to be a logistical hardship for veterinary facilities and staff. Thus, there is an unmet medical need for prevention, therapeutic treatment, and improved compositions for addressing the affliction of parvoviral infection in animals, for example, companion animals.

[0009] Feline panleukopenia virus (FPV) is closely related to CPV, as both viruses belong to the species Protoparvovirus camivoran 1. Because of their close relationship, itAttorney Reference No. 2920951-538977has been observed that CPV may infect cats and cause panleukopenia disease. On the other hand, FPV vaccines may protect cats against diseases caused by CPV.SUMMARY

[0010] In an aspect, the disclosure provides for a method of treating parvoviral infection in a companion animal. In aspects, the disclosure provides for a method of treating parvoviral infection in a feline with proteins, compositions, and antibodies described herein.

[0011] In aspects, methods described herein comprise administering to a feline a caninized antibody that unexpectedly binds to feline panleukopenia virus (FPV). In other aspects, the caninized antibodies with the same sequence binds to both feline panleukopenia virus (FPV) and canine parvovirus (CPV).

[0012] In aspects, the antibody binds to CPV and / or FPV with a dissociation constant (Kd) of less than 5 x 10’6M, less than 1 x 10'6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10"8M, less than 1 x 10"8M, less than 5 x 10"9M, less than 1 x 10'9M, less than 5 x IO'10M, less than 1 x 10'10M, less than 5 x 10'11M, less than 1 x 10'11M, less than 5 x 10'12M, or less than 1 x 10'12M.

[0013] In aspects, the antibody binds to CPV and / or FPV with a Kd of between 5 x 10'6M and 1 x 10"6M, between 5 x 10'6M and 5 x 10'7M, between 5 x 10'6M and 1 x 10'7M, between 5 x 10"6M and 5 x 10"8M, between 5 x 10’6M and 1 x 10’8M, between 5 x 10'6M and 5 x 10'9M, between 5 x 10'6M and 1 x 10'9M, between 5 x 10'6M and 5 x 10'10M, between 5 x 10'6M and 1 x 10'10M, between 5 x 10'6M and 5 x 10'11M, between 5 x 10'6M and 1 x 10"11M, between 5 x 10'6M and 5 x 1012M, between 5 x 10'6M and 1 x 1012M, between 1 x 10"6M and 5 x 10"7M, between 1 x 10"6M and 1 x 10"7M, between 1 x 10’6M and 5 x 10'8M, between 1 x 10'6M and 1 x 10'8M, between 1 x 10'6M and 5 x 10"9M, between 1 x 10'6M and 1 x 10'9M, between 1 x 10’6M and 5 x IO’10M, between 1 x 10'6M and 1 x IO’10M, between 1 x 10'6M and 5 x 10'11M, between 1 x 10'6M and 1 x 10'11M, between 1 x 10"6M and 5 x 10"12M, between 1 x 10"6M and 1 x 10"12M, between 5 x 10"7M and 1 x 10’7M, between 5 x 10’7M and 5 x 10’8M, between 5 x 10'7M and 1 x 10'8M, between 5 x 10'7M and 5 x 10'9M, between 5 x 10’7M and 1 x 10’9M, between 5 x 10'7M and 5 x IO’10M, between 5 x 10'7M and 1 x 10'10M, between 5 x 10'7M and 5 x 10'11M, between 5 x 10"7M and 1 x 10"11M, between 5 x 10"7M and 5 x 10"12M, between 5 x 10"7M and 1 x IO’12M, between 1 x 10'7M and 5 x 10'8M, between 1 x 10'7M and 1 x 10'8M, between 1 x 10'7M and 5 x 10'9M, between 1 x 10’7M and 1 x 10’9M, between 1 x 10'7MAttorney Reference No. 2920951-538977and 5 x IO’10M, between 1 x 10'7M and 1 x 10'10M, between 1 x 10'7M and 5 x 10'11M, between 1 x 10‘7M and 1 x IO"11M, between 1 x 10‘7M and 5 x 10‘12M, between 1 x 10‘7M and 1 x IO’12M, between 5 x 10'8M and 1 x 10'8M, between 5 x IO'8M and 5 x 10'9M, between 5 x 10'8M and 1 x 10'9M, between 5 x IO’8M and 5 x IO'10M, between 5 x IO'8M and 1 x IO’10M, between 5 x IO'8M and 5 x IO'11M, between 5 x 10'8M and 1 x 10'11M, between 5 x 10‘8M and 5 x 10‘12M, between 5 x 10‘8M and 1 x 10‘12M, between 1 x 10‘8M and 5 x IO’9M, between 1 x IO'8M and 1 x 10'9M, between 1 x IO"8M and 5 x IO"10M, between 1 x 10'8M and 1 x 10'10M, between 1 x IO'8M and 5 x IO'11M, between 1 x IO'8M and 1 x IO’11M, between 1 x IO'8M and 5 x 10'12M, between 1 x 10'8M and 1 x 10'12M, between 5 x 10'9M and 1 x 10'9M, between 5 x 10’9M and 5 x IO’10M, between 5 x 10'9M and 1 x IO’10M, between 5 x 10'9M and 5 x 10'11M, between 5 x 10'9M and 1 x 10'11M, between 5 x 10"9M and 5 x 10"12M, between 5 x 10'9M and 1 x 10'12M, between 1 x 10'9M and 5 x IO’10M, between 1 x 10'9M and 1 x IO'10M, between 1 x 10'9M and 5 x 10'11M, between 1 x 10'9M and 1 x 10'11M, between 1 x 10'9M and 5 x 10'12M, between 1 x 10'9M and 1 x 10’12M, between 5 x IO'10M and 1 x IO"10M, between 5 x IO’10M and 5 x IO’11M, between, 1 x IO'10M and 5 x IO'11M, between 1 x IO'10M and 1 x IO'11M, between 1 x IO'10M and 5 x 10'12M, between 1 x IO'10M and 1 x 10'12M, between 5 x IO'11M and 1 x 10'12M, between 5 x 10'11M and 5 x 10'12M, between 5 x IO'11M and 1 x 10'12M, between 1 x IO"11M and 5 x 1012M, or between 1 x IO"11M and 1 x 1012M.

[0014] In a further aspect, antibodies described herein that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise:(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5, (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 6, and (b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0015] In aspects, one or more of SEQ ID NO: 4, 5, 6, 13, 14, or 15 optionally comprise one, two, or three amino acid substitutions. In aspects, the amino acid substitutions are conservative substitutions.

[0016] In aspects, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises:(a) (i) a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 7 or 8,Attorney Reference No. 2920951-538977(ii) a HC-FR2 comprising the amino acid sequence of SEQ ID NO: 9, (iii) a HC-FR3 comprising the amino acid sequence of SEQ ID NO: 10, (iv) a HC-FR4 comprising the amino acid sequence of SEQ ID NO: 11 or 12, and(b) (i) a LC-FR1 comprising the amino acid sequence of SEQ ID NO: 16, (ii) a LC-FR2 comprising the amino acid sequence of SEQ ID NO: 17, (iii) a LC-FR3 comprising the amino acid sequence of SEQ ID NO: 18, and (iv) a LC-FR4 comprising the amino acid sequence of SEQ ID NO: 19.

[0017] In aspects, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises: a variable heavy chain sequence of SEQ ID NO: 20, 21, 85, or 86; and a variable light chain sequence of SEQ ID NO: 22 or 87.

[0018] In a further aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 23, 24, 37, or 38; and a light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25 or 39. In a further aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 24; and a light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25.

[0019] In others aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises a heavy chain sequence comprises SEQ ID NO: 24 and a light chain sequence comprises SEQ ID NO: 25, wherein SEQ ID NO: 24 and / or SEQ ID NO: 25 optionally comprise one, two, three, four, five, ten, or twenty amino acid substitutions. In aspects, the amino acid substitutions are conservative substitutions.

[0020] In a further aspect, antibodies described herein that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise:(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 42, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 43, (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 44, and (b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53, and (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 54.Attorney Reference No. 2920951-538977

[0021] In aspects, one or more of SEQ ID NO: 42,43, 44, 52, 53, or 54 optionally comprise one, two, or three amino acid substitutions. In aspects, the amino acid substitutions are conservative substitutions.

[0022] In aspects, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises:(a) (i) a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 45 or 46, (ii) a HC-FR2 comprising the amino acid sequence of SEQ ID NO: 47 or 48, (iii) a HC-FR3 comprising the amino acid sequence of SEQ ID NO: 49 or 50, (iv) a HC-FR4 comprising the amino acid sequence of SEQ ID NO: 51, and (b) (i) a LC-FR1 comprising the amino acid sequence of SEQ ID NO: 55 or 56, (ii) a LC-FR2 comprising the amino acid sequence of SEQ ID NO: 57, (iii) a LC-FR3 comprising the amino acid sequence of SEQ ID NO: 58 or 59, and(iv) a LC-FR4 comprising the amino acid sequence of SEQ ID NO: 60 or 61.

[0023] In aspects, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises: a variable heavy chain sequence of SEQ ID NO: 62, 63, or 88; and a variable light chain sequence of SEQ ID NO: 64, 65, or 89.

[0024] In a further aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 66, 67, or 79; and a light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 68, 69, or 80.

[0025] In others aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprises a heavy chain sequence comprises SEQ ID NO: 66, 67, or 79 and a light chain sequence comprises SEQ ID NO: 68, 69, or 80, wherein SEQ ID NO: 66, 67, or 79 and / or SEQ ID NO: 68, 69, or 80 optionally comprise one, two, three, four, five, ten, or twenty amino acid substitutions. In aspects, the amino acid substitutions are conservative substitutions.

[0026] In aspects, the disclosure provides for compositions comprising, consisting essentially of, or consisting of antibodies described herein; a buffering agent; an isotonic agent; and a surfactant.

[0027] In aspects, compositions described herein result in improved stability and shelflife.Attorney Reference No. 2920951-538977

[0028] In aspects, compositions described herein comprise a chimeric antibody. In other aspects, compositions described herein comprise a canine or feline constant heavy chain region and / or a canine or feline constant light chain region.

[0029] In further aspects, compositions described herein comprise:(a) a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region; or(b) a feline heavy chain constant region selected from an IgGl, IgG2a, and IgG2b constant region.

[0030] In aspects, compositions described herein comprise a canine K light constant region or a feline K light constant region.

[0031] In additional aspects, compositions described herein comprise antibodies which bind to an epitope comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and / or SEQ ID NO: 3.

[0032] In aspects, the disclosure provides for compositions comprising, consisting essentially of, or consisting of antibodies described herein; a buffering agent; an isotonic agent; and a surfactant.

[0033] In an aspect, the buffering agent comprises histidine and / or citrate.

[0034] In an aspect, the isotonic agent comprises mannitol, sorbitol, maltitol, glycerol, sucrose, glucose, dextrose, levulose, fructose, lactose, polyethylene glycols 400 to 4000, phosphates, sodium chloride, potassium chloride, calcium chloride, calcium gluconoglucoheptonate, and / or dimethyl sulfone. In some embodiments, the isotonic agent comprises sucrose.

[0035] In an aspect, the surfactant comprises poloxamer-188 and / or polysorbate-20.

[0036] In a further aspect, compositions described herein comprise at least one antioxidant. In a further aspect, the antioxidant is methionine. In yet further aspects, the composition comprises a chelating agent. In a further aspect, the chelating agent comprises ethylenediaminetetraacetic acid (EDTA). In an aspect, the composition does not comprise sodium chloride (NaCl). In a further aspect, compositions described herein comprise a stabilizer. In a further aspect, the stabilizer comprises NaCl, arginine, methionine, EDTA, and / or glycine.

[0037] In a further aspect, compositions described herein comprise a preservative. In a further aspect, the preservative comprises one or more of: benzalkonium chloride, benzoic acid, benzyl alcohol, benzyl benzoate, boric acid, chlorobutanol, parabens (such as methylparaben and propylparaben), phenol, sodium sorbate, potassium sorbate, sodiumAttorney Reference No. 2920951-538977benzoate, sorbic acid, thimerosal, sulfur dioxide, sulfites, nitrites, nitrates, lactic acid, propionic acid, propionates, phosphoric acid, ascorbic acid, sodium ascorbate, butylated hydroxytoluene, butylated hydroxyanisole, gallic acid, sodium gallate, tocopherols, citric acid, citrates, tartaric acid, and / or lecithin.

[0038] In an aspect, compositions described herein are suitable for injection to the companion animal. In aspects, compositions described herein are administered parenterally, by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, an intravenous, an inhalation route, or parenterally, or orally. In a preferred aspect, compositions described herein are administered by a subcutaneous route. In other aspects, compositions described herein are administered by a subcutaneous route in a single dose.

[0039] In aspects, compositions described herein are administered in an amount in the range of 0.01 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 0.5 mg / kg body weight to 100 mg / kg body per dose, in the range of 1 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 5 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 10 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 20 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 50 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 1 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 5 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 0.5 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 0.01 mg / kg body weight to 0.5 mg / kg body weight per dose, in the range of 0.01 mg / kg body weight to 0.1 mg / kg body weight per dose, or in the range of 5 mg / kg body weight to 50 mg / kg body weight per dose.

[0040] In aspects, compositions described herein are administered at least once per week, at least twice per week, at least thrice per week, at least four times per week, at least five times per week, at least six times per week, or at least seven times per week.

[0041] In aspects, compositions described herein are administered at least two consecutive weeks, at least three consecutive weeks, at least four consecutive weeks, at least five consecutive weeks, at least six consecutive weeks, at least seven consecutive weeks, at least eight consecutive weeks, at least nine consecutive weeks, at least ten consecutive weeks, at least eleven consecutive weeks, or at least twelve consecutive weeks.

[0042] In aspects, compositions described herein are administered in a single dose. In additional aspects, compositions described herein are administered in a single dose once a week, once every two weeks, once every three weeks, or once every month. In other aspects,Attorney Reference No. 2920951-538977compositions described herein are administered in two or three doses. In further aspects, compositions described herein are administered in two or three doses over the course of one, two, or three months.

[0043] In other aspects, compositions described herein are in liquid form and not frozen. In aspects, compositions described herein do not need to be thawed prior to use.

[0044] In an aspect, the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) is present in an amount of about 0.001% to about 0.1% (w / v), about 0.001% to about 0.05% (w / v), about 0.01% to about 0.05% (w / v), about 0.05% to about 0.5% (w / v), or about 0.01% to about 1% (w / v) relative to the total weight of the composition.

[0045] In another aspect, the antibody that binds to canine parvovirus and / or feline parvovirus is present in an amount of about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 25 mg / ml, about 3 mg / ml to about 40 mg / ml, about 1 mg / ml to about 10 mg / ml, about 2 mg / ml to about 8 mg / ml, about 4 mg / ml to about 6 mg / ml, about 25 mg / ml to about 35 mg / ml, about 10 mg / ml to about 20 mg / ml, or about 28 mg / ml to about 32 mg / ml. In another aspects, the antibody that binds to canine parvovirus and / or feline parvovirus is present in an amount of about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 6 mg / ml, about 7 mg / ml, about 8 mg / ml, about 9 mg / ml, about 10 mg / ml, about 20 mg / ml, or about 25 mg / ml.

[0046] In an aspect, the buffering agent is present in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition.

[0047] In an aspect, the isotonic agent is present in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v), relative to the total weight of the composition.

[0048] In an aspect, the surfactant is present in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition. In aspects, the surfactant is present in no more than about 0.02% (w / v), 0.05% (w / v), or 0.10% (w / v) relative to the total weight of the composition.

[0049] In a further aspect, the disclosure provides for a pharmaceutical composition comprising, consisting essentially of, or consisting of an administrable solution comprising:Attorney Reference No. 2920951-538977a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV); b) a buffering agent; c) an isotonic agent; and d) a surfactant.

[0050] In an aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), about 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) a buffering agent in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) a surfactant in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0051] In an aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), wherein the antibody is present in an amount of about 10 mg / ml to about 50 mg / ml, 15 mg / ml to about 45 mg / ml, 20 mg / ml to about 40 mg / ml, 25 mg / ml to about 35 mg / ml, 10 mg / ml to about 20 mg / ml, or 28 mg / ml to about 32 mg / ml;b) a buffering agent in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andAttorney Reference No. 2920951-538977d) a surfactant in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0052] In an aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody comprising an amino acid sequence at least about 80%, 90%, 95%, 98%, or 99% identical to SEQ ID NO: 24 or SEQ ID NO: 25 in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), about 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) a buffering agent in an amount of about 0.30% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) a surfactant in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0053] In a further aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody comprising an amino acid sequence at least about 80%, 90%, 95%, 98%, or 99% identical to SEQ ID NO: 24 or SEQ ID NO: 25 in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), about 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) histidine in an amount of about 0.30% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) sucrose in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andAttorney Reference No. 2920951-538977d) poloxamer-188 in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0054] In a further aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), about 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition; relative to the total weight of the composition;b) histidine in an amount of about 0.30% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) sucrose in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10% (w / v), about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) poloxamer-188 in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0055] In a further aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) histidine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) methionine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;d) sucrose in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition;e) poloxamer-188 in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition; andAttorney Reference No. 2920951-538977f) ethylenediaminetetraacetic acid (EDTA) in an amount of about 0.001% to about 10% (w / v) relative to the total weight of the composition.

[0056] In another aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of from about 1 mg / ml to about 50 mg / mL;b) histidine in an amount of from about 10 mM to about 30 mM;c) sucrose in an amount from about 5% to about 10% (w / v); andd) poloxamer, for example poloxmer-188, in an amount from about 0.01 to about 0.05% (w / v).

[0057] In another aspect, the disclosure provides for a composition comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of from about 20 mg / mL to about 35 mg / mL;b) histidine in an amount of about 20 mM;c) sucrose in an amount of about 8% (w / v); andd) poloxamer- 188 in an amount of about 0.02% (w / v).

[0058] In a further aspect, the disclosure provides for a composition comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of from about 25 mg / mL to about 35 mg / mL;b) histidine in an amount of about 20 mM;c) sucrose in an amount of about 8% (w / v); andd) poloxamer- 188 in an amount of about 0.02% (w / v).

[0059] In a further aspect, the disclosure provides for a composition comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of from about 20 mg / mL to about 30 mg / mL;b) histidine in an amount of about 20 mM;c) methionine in an amount of about 5 mM;d) sucrose in an amount of about 8% (w / v); ande) poloxamer- 188 in an amount of about 0.02% (w / v).

[0060] In a further aspect, the disclosure provides for a composition comprising, consisting essentially of, or consisting of:Attorney Reference No. 2920951-538977a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of from about 5 mg / mL to about 25 mg / mL;b) histidine in an amount of about 20 mM;c) methionine in an amount of about 5 mM;d) sucrose in an amount of about 8% (w / v);e) poloxamer-188 in an amount of about 0.02% (w / v); andf) ethylenediaminetetraacetic acid (EDTA) in an amount of about 0.5 mM.

[0061] In aspects, antibodies described herein that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise CDR chains from SEQ ID NO: 4, 5, 6, 13, 14, and 15. In another aspects, antibodies described herein that bind canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise an amino acid sequence at least about 80%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 24 or SEQ ID NO: 25.

[0062] In aspects, antibodies described herein that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise CDR chains from SEQ ID NO: 42, 43, 44, 52, 53, and 54. In another aspects, antibodies described herein that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) comprise an amino acid sequence at least about 80%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 67 or SEQ ID NO: 68.

[0063] In aspects, antibodies described herein are monoclonal antibodies. In additional aspects, compositions described herein comprise monoclonal antibodies.

[0064] In aspects, compositions described herein are stable at about 6 months or more, about 9 months or more, or about 12 months or more at about 2°C - 8°C.

[0065] In other aspects, compositions comprising antibodies that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 30 mg / mL concentration are stable at about 6 months or more, about 9 months or more, or about 12 months are more at 2°C - 8°C. In further aspects, compositions comprising antibodies comprising amino acid sequences at least about 80%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 24 and SEQ ID NO: 25 in an amount of about 20 to about 30 mg / mL concentration are stable at about 6 months or more, about 9 months or more, or about 12 months are more at about 2°C - 8°C.

[0066] In aspects, the disclosure provides for compositions comprising antibodies that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), wherein the composition is stable and / or shelf-stable for more than about one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, tenAttorney Reference No. 2920951-538977months, eleven months, twelve months, two years, three years, or four years or more at about 2°C - 8°C.

[0067] In aspects, the disclosure provides for compositions comprising antibodies that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), wherein the composition is stable or shelf-stable about twelve months at an antibody concentration of about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 25 mg / ml, about 3 mg / ml to about 40 mg / ml, about 1 mg / ml to about 10 mg / ml, about 2 mg / ml to about 8 mg / ml, about 4 mg / ml to about 6 mg / ml, about 25 mg / ml to about 35 mg / ml, about 10 mg / ml to about 20 mg / ml, about 28 mg / ml to about 32 mg / ml, about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 6 mg / ml, about 7 mg / ml, about 8 mg / ml, about 9 mg / ml, about 10 mg / ml, about 20 mg / ml, or about 25 mg / ml at 2°C - 8°C. In further aspects, the disclosure provides for compositions comprising antibodies comprising amino acid sequences at least about 80%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 24 and SEQ ID NO: 25, wherein the composition is stable or shelf-stable about twelve months at an antibody concentration of about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 25 mg / ml, about 3 mg / ml to about 40 mg / ml, about 1 mg / ml to about 10 mg / ml, about 2 mg / ml to about 8 mg / ml, about 4 mg / ml to about 6 mg / ml, about 25 mg / ml to about 35 mg / ml, about 10 mg / ml to about 20 mg / ml, or about 28 mg / ml to about 32 mg / ml, about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 6 mg / ml, about 7 mg / ml, about 8 mg / ml, about 9 mg / ml, about 10 mg / ml, about 20 mg / ml, or about 25 mg / ml at about 2 - 8° C.

[0068] The disclosure further provides for methods of improving stability comprising using compositions and antibodies described herein. In aspects, the use of histidine from pH 7 - 7.5, pH 7 - 7.3, pH 7 - 7.2, pH 7.1 - 7.3, or pH 7.2 improves the stability of parvovirus compositions described herein. In other aspects, the use of histidine from pH 7 - 7.5, pH 7 -7.3, pH 7 - 7.2, pH 7.1 - 7.3, or pH 7.2 improves the stability of parvovirus compositions described herein compared to buffers comprising phosphate at the same pH. In aspects, buffers described herein comprise histidine and not phosphate.

[0069] In aspects, buffers comprising histidine and buffers comprising citrate improve stability of compositions described herein similarly across pH 6 - 7, whereas the use of histidine from pH 7 - 7.5, pH 7 - 7.3, pH 7 - 7.2, pH 7.1 - 7.3, pH 7.2 - 7.4, or pH 7.2 improves the stability of parvovirus compositions described herein vs. citrate. Formulations with excipients 5% sucrose, 2 mM methionine and 0.5 mM EDTA show improved stability at 2°C - 8°C.Attorney Reference No. 2920951-538977

[0070] In aspects, parvovirus antibodies and compositions described herein showed improved stability at 2°C - 8°C when formulated in compositions comprising histidine at pH 7.2, 5% sucrose, 2 mM methionine, and 0.5 mM EDTA. In aspects, compositions comprising canine parvovirus antibody comprising SEQ ID NO: 24 and 25 parvovirus antibodies, histidine at pH 7.2, 5% sucrose, 2 mM methionine, and 0.5 mM EDTA exhibit improved stability at 2°C - 8°C. In aspects, the improved stability is over about one, two, three, four, five, or six months or more.

[0071] In aspects, compositions described herein reduce particulate formation and / or subvisible particulate formation. In further aspects, compositions described herein with poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through six months of shelflife.

[0072] In aspects, compositions described herein reduce particulate formation and / or subvisible particulate formation, where the particulates are smaller than about 1 pm, 10pm, or 25pm. In further aspects, compositions described herein reduce particulate formation and / or subvisible particulate formation, wherein the particulates are about 1pm to 10pm or about 10pm to 25pm. In further aspects, compositions described herein comprise less than about 100, less than about 200, less about 500, or less than about 1000 particles (particle / mL) and wherein the particles have a size from about 1pm to 10 pm or about 10 pm to 25 pm, after about 50 days, 60 days, 70 days, 80 days, 100 days, or 120 days. In aspects, the storage temperature is at 2°C - 8°C.

[0073] In further aspects, compositions described herein with poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through six months of shelf life.

[0074] In aspects, compositions described herein comprising poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through 6 months of shelf life. In aspects compositions comprising 8% w / v sucrose, 2 mM methionine, 0.5 mM EDTA, and 0.02%w / v poloxamer-188 exhibited improved stability after one, two, three, four, five, six, seven, eight, nine, ten, eleven, or more than twelve months. In aspects, compositions comprising canine parvovirus antibody comprising SEQ ID NO: 24 and 25 parvovirus antibodies, 8% w / v sucrose, 2 mM methionine, 0.5 mM EDTA, and 0.02% w / v poloxamer-188 exhibit improved stability at 2°C - 8°C after one, two, three, four, five, six, seven, eight, nine, ten, eleven, or more than twelve months or more.Attorney Reference No. 2920951-538977

[0075] In aspects, compositions described herein further comprise a pharmaceutically acceptable carrier. In some aspects, the pharmaceutically acceptable carrier is phosphate buffered saline (PBS).

[0076] In aspects, compositions described herein further comprise phosphate buffered saline (PBS). In further aspects, compositions described herein further comprise phosphate buffered saline (PBS) at a pH of about 7.2.

[0077] In a further aspect, the disclosure provides for a method for treatment of a parvoviral infection in a feline, the method comprising administering to the feline a therapeutically effective amount of a pharmaceutical composition comprising an administrable solution comprising, consisting essentially of, or consisting of: a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV); b) a buffering agent; c) an isotonic agent; and d) a surfactant.

[0078] In an aspect, the disclosure provides for methods for treatment of a parvoviral infection in a feline, the method comprising administering to the feline a therapeutically effective amount of a composition comprising, consisting essentially of, or consisting of: a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV); b) a buffering agent; c) an isotonic agent; and d) a surfactant.

[0079] In an aspect, the disclosure provides for isolated nucleic acid sequences encoding antibodies described herein. Host cells comprising the nucleic acid described herein are also provided.

[0080] In an aspect, the disclosure provides for compositions described herein that provides passive immunity against infection with canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), and / or treating parvoviral infection in a feline. Antibodies described herein may be used in compositions described herein.

[0081] The disclosure further provides for methods of treating a canine or feline parvoviral infection in a subject comprising administering to the subject a therapeutically effective amount of an antibody or composition described herein that binds to the canine or feline parvovirus.

[0082] In aspects, antibodies and compositions described herein are administered parenterally or subcutaneously.

[0083] In further aspects, antibodies and compositions described herein are administered by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, or an intravenous route.Attorney Reference No. 2920951-538977

[0084] In aspects, antibodies and compositions described herein are administered before exposure to the canine or feline parvovirus. In further aspects, antibodies and compositions described herein are administered after exposure to the canine parvovirus (CPV) and / or feline panleukopenia virus (FPV).

[0085] The disclosure further provides for administering antibodies and compositions described herein after infection with the canine parvovirus (CPV) and / or feline panleukopenia virus (FPV).

[0086] In further aspects, antibodies and compositions described herein are administered after the subject, for example a cat, has exhibited at least one symptoms selected from fever, vomiting, diarrhea, lymphopenia / leukopenia, septicemia, dehydration, loss of appetite, abdominal pain, lethargy, depression, and / or nasal discharge.

[0087] In aspects, antibodies and compositions described herein are administered after canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) has been detected in feces, such as determined by a positive cage-side SNAP test. In aspects, the subject has previously been administered a parvovirus vaccine.

[0088] In aspects, the subject, for example a cat, has not previously been administered a parvovirus vaccine. In further aspects, the subject, for example a cat, is unprotected at birth due to lack of maternally-derived antibodies to a canine or feline parvovirus or failure of passive transfer of antibodies to a canine or feline parvovirus. In further aspects, the subject, for example a cat, is hand-reared, the subject’s mother does not produce milk, or the subject is unable to produce antibodies against parvovirus.

[0089] In further aspects, the subject, for example a cat, is living in an environment contaminated with the canine parvovirus (CPV) and / or feline panleukopenia virus (FPV). BRIEF DESCRIPTION OF THE DRAWINGS

[0090] FIG. 1 is a diagram of the window of susceptibility for CPV.

[0091] FIG. 2 shows Mab A v2 and Mab B v2 binding to VP2.

[0092] FIG. 3 depicts stability of canine parvovirus in different buffer systems.

[0093] FIG. 4, FIG. 5, and FIG. 6 depict the results of SEC monomer testing for canine parvovirus antibody compositions with or without stabilizing excipients.

[0094] FIG. 7 and FIG. 8 depict particulate formation during freeze / thaw cycles in canine parvovirus antibody compositions using MFI assays.Attorney Reference No. 2920951-538977

[0095] FIG. 9 evaluates canine parvovirus antibody compositions with various excipient combinations using a cIEF assay. Canine parvovirus antibody formulations F1-F8 are described in Table 11.

[0096] FIG. 10 depicts fragmentation of canine parvovirus in combinations using a CE-SDS assay. Canine parvovirus antibody formulations F1-F8 are described in Table 11.

[0097] FIGs. 11 and 12 depict the impact of methionine and EDTA on subvisible particulates in canine parvovirus antibody compositions. Canine parvovirus antibody formulations F3-F7 are described in Table 11.

[0098] FIGs. 13, 14, and 15 depict the impact of poloxamer-188 and polysorbate-20 on subvisible particulates in canine parvovirus antibody compositions. Canine parvovirus antibody formulations F3 and F4 are described in Table 11.

[0099] FIGs. 16 and 17 depict the impact of poloxamer-188 and polysorbate-20 on changes in percent monomer and percent aggregate of canine parvovirus antibody in formulation compositions using an SEC-HPLC assay. Canine parvovirus antibody formulations F1-F8 are described in Table 11.

[0100] FIGs. 18, 19, and 20 depict stability of canine parvovirus antibody in compositions with various excipient combinations using an SEC monomer assay for 7 months at 2-8 °C. Canine parvovirus antibody formulations F1-F8 are described in Table 11.

[0101] FIGs. 21 and 22 depict the results of an agitation study conducted to evaluate the impact of surfactant type, surfactant level, and EDTA quantity on particulate formation in canine parvovirus antibody compositions.

[0102] FIGs. 23 and 24 depict the results of a hydrogen peroxide (H2O2) spiking study used to determine oxidation impact and particulate formation for surfactants polysorbate-20 and poloxamer-188 in the presence of free methionine and / or EDTA.

[0103] In each of Figures 3 - 24, the canine parvovirus described comprises Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25).

[0104] FIGs. 25A and 25B depict the results of the in vitro cellular viral infection assay of canine parvovirus monoclonal antibody (Mab A v2) against CPV and FPV.Attorney Reference No. 2920951-538977DESCRIPTION OF CERTAIN SEQUENCES

[0105] Table 1 provides a listing of certain sequences referenced herein.Table 1.Description of Certain SequencesSEQ ID SEQUENCE DESCRIPTION NO:1 ESENYRRVWNNMDKTAVNGNMALDDIHAEIVT Epitope 1PWSLV2 TPWRYYFQWDRTLIPSHTGTSGTPTNIYHGTDPD Epitope 2 DVQFYTIENS3 TPWRYYFQWDRTLIPSHTGTSGTP Minimal epitope 24 GFSLSSYHVH Variable heavy chain CDR-H1 of Mab A 5 VMWNDGDTS Variable heavy chain CDR-H2 of Mab A 6 PELPGLTYGVWFPY Variable heavy chain CDR-H3 of Mab A 7 QVQLKESGPGLVQPSQTLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab A8 QVQLKESGPGLVAPSQTLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab A variant 2 (v2) Q13A9 WVRQPPGKGLEWLG Variable region heavy chain framework region HC-FR2 of Mab A10 YNLALNSRLSISRDTSKSQVFFKMSSLQTEDTATY Variable heavy chain YCAR framework region HC-FR3 of Mab A11 WGQGTLVTVSS Variable heavy chain framework region HC-FR4 of Mab A12 WGQGTLVTVSA Variable heavy chain framework region HC-FR4 of Mab A variant 2 (v2) S11A13 KASQNVDSNVD Variable light chain CDR-L1 of Mab A 14 KASNRNT Variable light chainCDR-L2 of Mab AAtorney Reference No. 2920951-538977MQSTSYPLTF Variable light chain CDR-L3 of Mab A Z>7EMTQ7? ASMSISVGDRVTMNC Variable light chain framework region LC-FR1 of Mab A WYQQKTGQSPNLLIY Variable light chain framework region LC-FR2 of Mab A GVPDRFTGSGSGTDFTFTISNMQAEDLAVYYC Variable light chain framework region LC-FR3 of Mab A GSGTKLEIK Variable light chain framework region LC-FR4 of Mab A QVQLKESGPGLVQPSQTLSLTCTVSGFSLSSYHVH Variable heavy chain of WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL Mab A SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG LTYGVWFPYWGQGTLVTVSS (Mab A HC) QVQLKESGPGLVAPSQTLSLTCTVSGFSLSSYHVH Variable heavy chain of WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL Mab A variant 2 SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG LTYGVWFPYWGQGTLVTVSA HC-FR1 Q13AHC-FR4 S11A (MabAHCv2) DIVMTQSPTSMSISVGDRVTMNCKASQNVDSNV Variable light chain of Mab DWYQQKTGQSPKLLIYKASNRNTGVPDRFTGSG A SGTDFTLTISNMQAEDLAVYYCMQSTSYPLTFGS GTKLEIK (MabALC) QVQLKESGPGLVQPSQTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL chain of Mab A and canine SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG IgG-B LTYGVWFPYWGQGTLVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG(Chimeric A HC IgG-B) VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN VAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAP EMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR WSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT QESLSHSPGK QVQLKESGPGLVAPSQTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL chain of Mab A v2 and SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG canine IgG-B LTYGVWFPYWGQGTLVTVSAASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG HC-FR1 Q13A VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN HC-FR4 S11AVAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPAtorney Reference No. 2920951-538977EMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR (Chimeric A HC v2 IgG-B) WSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT QESLSHSPGKDIVMTQSPTSMSISVGDRVTMNCKASQNVDSNV Chimeric variable light DWYQQKTGQSPKLLIYKASNRNTGVPDRFTGSGS chain of Mab A and canine GTDFTLTISNMQAEDLAVYYCMQSTSYPLTFGSG K light constant region TKLEIKRNDAQPAVYLFQPSPDQLHTGSASWCL LNSFYPKDINVKWKVDGVIQDTGIQESVTEQDKD (Chimeric A LC K) STYSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLI KSFQRSECQRVDMAVLGLLLCLVTFPSCVLS Heavy chain leader METDTLLLWVLLLWVPGSTG Light chain leader MAVLGLLLCLVTFPSCVLSQVQLKESGPGLVQPSQ Chimeric variable heavy TLSLTCTVSGFSLSSYHVHWVRQPPGKGLEWLGV chain of Mab A and canine MWNDGDTSYNLALNSRLSISRDTSKSQVFFKMSS IgG-B with leader sequence LQTEDTATYYCARPELPGLTYGVWFPYWGQGTL VTVSSASTTAPSVFPLAPSCGSTSGSTVALACLVS GYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLYSL SSMVTVPSSRWPSETFTCNVAHPASKTKVDKPVP (Chimeric A HC IgG-B with KRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPK leader) DTLLIARTPEVTCVWDLDPEDPEVQISWFVDGK QMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLK GKQFTCKVNNKALPSPIERTISKARGQAHQPSVYV LPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ RGDTFICAVMHEALHNHYTQESLSHSPGK MAVLGLLLCLVTFPSCVLSQVQLKESGPGLVAPSQ Chimeric variable heavy TLSLTCTVSGFSLSSYHVHWVRQPPGKGLEWLGV chain of Mab A v2 and MWNDGDTSYNLALNSRLSISRDTSKSQVFFKMSS canine IgG-B with leader LQTEDTATYYCARPELPGLTYGVWFPYWGQGTL sequence VTVSAASTTAPSVFPLAPSCGSTSGSTVALACLVS GYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLYSL SSMVTVPSSRWPSETFTCNVAHPASKTKVDKPVP HC-FR1 Q13A KRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPK HC-FR4 S11A DTLLIARTPEVTCVWDLDPEDPEVQISWFVDGK QMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLK (Chimeric A HC v2 IgG-B GKQFTCKVNNKALPSPIERTISKARGQAHQPSVYV with leader) LPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ RGDTFICAVMHEALHNHYTQESLSHSPGKAtorney Reference No. 2920951-538977METDTLLLWVLLLWVPGSTGZ>7n / T(J7? ASMSIS Chimeric variable light VGDRVTMNCKASQNVDSNVDWYQQKTGQSPNL chain of Mab A and canine LTYKASNRNTGVPDRFTGSGSGTDFTFTISNMQAE K light constant region with DLAVYYCMQSTSYPLTFGSGTKLEIKRNDAQPAV leader sequence YLFQPSPDQLHTGSASWCLLNSFYPKDINVKWK VDGVIQDTGIQESVTEQDKDSTYSLSSTLTMSSTE YLSHELYSCEITHKSLPSTLIKSFQRSECQRVD (Chimeric A LC K with leader) QVQLKESGPGLVQPSQTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL chain of Mab A and feline SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG IgG-1 LTYGVWFPYWGQGTLVTVSSASTTAPSVFPLAPS CGTTSGATVALACLVLGYFPEPVTVSWNSGALTS (Chimeric A HC IgG-1) GVHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFT CNVAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCP PPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLG PDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYR WSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTIS KAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSF HPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQ KSLTQSPGKD / FA / T’gT’PASMSISVGDRVTMNCKASQNVDSNVD Chimeric variable light WYQQKTGQSPNLLIYKASNRNTGVPDRFTGSGSG chain of Mab A and feline K TDFTFTISNMQAEDLAVYYCMQSTSYPLTFGSGT light constant region KLEIKRSDAQPSVFLFQPSLDELHTGSASIVCILND FYPKEVNVKWKVDGWQNKGTQESTTEQNSKDS (Chimeric A LC K) TYSLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLV KSFNRSECQREDIVMTQTPASMSISVGDRVTMNCKASQNVDSNVD Chimeric variable light WYQQKTGQSPNLLIYKASNRNTGVPDRFTGSGSG chain of Mab A and feline K TDFTFTISNMQAEDLAVYYCMQSTSYPLTFGSGT light constant region with no KLEIKRSDAQPSVFLFQPSLDELHTGSASIVCILND N-linked glycosylation site FYPKEVNVKWKVDGWQNKGIQESTTEQNSKDS TYSLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLV KSFQRSECQRE (Chimeric A LC K aglycos) MAVLGLLLCLVTFPSCVLSQVQLVESGGDLVKPG Caninized variable heavy GTLRLSCTVSGFSLSSYHVHWVRQPPGKGLEWVA chain of Mab A v3 and VMWNDGDTSYNLAVKGRFTTSRDNAKNTLYLQM canine IgG-B with leader NSLRAEDTAVYYCARPELPGLTYGVWFPYWGQG sequence TLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACL VSGYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLY SLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKP (Chimeric A HC v3 IgG-B VPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPK with leader) PKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDG KQMQTAKTQPREEQFNGTYRWSVLPIGHQDWL KGKQFTCKVNNKALPSPIERTISKARGQAHQPSVY VLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNG QQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGKAtorney Reference No. 2920951-538977QVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV Caninized variable heavy HWVRQPPGKGLEWVAVMWNDGDTSYNLAVKG chain of Mab A v3 RFTISRDNAKNTLYLQMNSLRAEDTAVYYCARPE LPGLTYGVWFPYWGQGTLVTVSS MAVLGLLLCLVTFPSCVLSEVQLVESGGDLVKPG Caninized variable heavy GTLRLSCTVSGFSLSSYHVHWVRQPPGKGLEWLG chain of Mab A v4 and VMWNDGDTSYNLAVKGRFTISRDNAKNTLYFQM canine IgG-B with leader NSLRAEDTATYYCARPELPGLTYGVWFPYWGQG sequence TLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACL VSGYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLY SLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKP (Caninized A HC v4 IgG-B VPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPK with leader) PKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDG KQMQTAKTQPREEQFNGTYRWSVLPIGHQDWL KGKQFTCKVNNKALPSPIERTISKARGQAHQPSVY VLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNG QQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRW QRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV Caninized variable heavy HWVRQPPGKGLEWLGVMWNDGDTSYNLAVKG chain of Mab A v4 RFTISRDNAKNTLYFQMNSLRAEDTATYYCARPE LPGLTYGVWFPYWGQGTLVTVSS METDTLLLWVLLLWVPGSTGEIVMTQSPASLSLS Caninized variable light QEEKVTITCKASQNVDSNVDWYQQKPGQAPKLLI chain of Mab A and canine YKASNRNTGVPSRFSGSGSGTDFSFTISSLEPEDVA K light constant region with VYYCMQSTSYPLTFGQGTKLEIKRNDAQPAVYLF leader sequence QPSPDQLHTGSASWCLLNSFYPKDINVKWKVDG VIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLSH ELYSCEITHKSLPSTLIKSFQRSECQRVD (Caninized A LC K with leader) EIVMTQSPASLSLSQEEKVTITCKASQNVDSNVD Caninized variable light WYQQKPGQAPKLLIYKASNRNTGVPSRFSGSGSG chain of Mab A TDFSFTISSLEPEDVAVYYCMQSTSYPLTFGQGTK LEIK QVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV Caninized variable heavy HWVRQPPGKGLEWVAVMWNDGDTSYNLAVKG chain of Mab A v3 and RFTISRDNAKNTLYLQMNSLRAEDTAVYYCARPE canine IgG-B LPGLTYGVWFPYWGQGTLVTVSSASTTAPSVFPL APSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSL (Caninized A HC v3 IgG-B) TSGVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETF TCNVAHPASKTKVDKPVPKRENGRVPRPPDCPKC PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCWVD LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGKAtorney Reference No. 2920951-538977EVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV Caninized variable heavy HWVRQPPGKGLEWLGVMWNDGDTSYNLAVKG chain of Mab A v4 and RFTISRDNAKNTLYFQMNSLRAEDTATYYCARPE canine IgG-B LPGLTYGVWFPYWGQGTLVTVSSASTTAPSVFPL APSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSL (Caninized A HC v4 IgG-B) TSGVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETF TCNVAHPASKTKVDKPVPKRENGRVPRPPDCPKC PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCWVD LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGK EIVMTQSPASLSLSQEEKVTITCKASQNVDSNVD Caninized variable light WYQQKPGQAPKLLIYKASNRNTGVPSRFSGSGSG chain of Mab A and canine TDFSFTISSLEPEDVAVYYCMQSTSYPLTFGQGTK K light constant region LEIKRNDAQPAVYLFQPSPDQLHTGSASWCLLNS FYPKDINVKWKVDGVIQDTGIQESVTEQDKDSTY(Caninized A LC K) SLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQ RSECQRVD QLTLRESGPGLVKPSQSLSLTCTVSGFSLSSYHVH Felinized variable heavy WIRQRPGRGLEWLGVMWNDGDTSYAFQGRISIT chain of Mab A ADTAQNQFSLQLSSMTTDDTAVYYCARPELPGLT YGVWFPYWGQGALVTVS (Felinized ARC) AITMTQSPGSLAGSPGQQVTMNCKASQNVDS Felinized variable light NVDWYQQKPGQHPKLLIYKASNRNTGVPDR chain of Mab A FSGSGSGTDFTLTISNLQAEDVASYYCMQSTS YPLTFGQGTKLEIK (Felinized A LC) GFSLTSYGVS Variable heavy chain CDR-H1 of Mab B TMWNDGDTD Variable heavy chain CDR-H2 of Mab B SQLPGYNLRGWFVY Variable heavy chain CDR-H3 of Mab B QVQLKESGPGLVQPSQTLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab B QVQLKESGPGLVQPSETLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab B variant 2 (v2) Q16E WVRQPPGKGLEWIG Variable region heavy chain framework region HC-FR2of Mab BAtorney Reference No. 2920951-538977 WVRQPPGKGLEWMG Variable region heavy chain framework region HC-FR2 of Mab B variant 2 (v2) I13M YHSALRSRLSISRDSSKSQVLLKMNSLQTEDTAM Variable heavy chain YFCAR framework region HC-FR3 of Mab B YNSALRSKLSISRDTSKSQVFLKMNSLQTEDTAIY Variable region heavy chain YCAR framework region HC-FR3 of Mab B variant 2 (v2) H2NR8KS15TL21FM34IF36YWGQGTLVIVS Variable heavy chain framework region HC-FR4 of Mab B KASHNINKNLE Variable light chain CDR-L1 of Mab B YANNLQT Variable light chain CDR-L2 of Mab B YQYNSGHTF Variable light chain CDR-L3 of Mab B n / PMT’eEPSLLSASVGDRVTLNC Variable light chain framework region LC-FR1 of Mab B DIQMTQSPPVLSASVGDRVTLSC Variable light chain framework region LC-FR1 of Mab B variant 2 (v2) V3QT7SS9PL10VN22S WYQQKLGEAPKLLIY Variable light chain framework region LC-FR2 of Mab B GISSRFSGSGSGTDYTLTISSLQPEDVATYYC Variable light chain framework region LC-FR3 of Mab B GIPSRFSGSGSGTDYTLTISSLQPEDVATYYC Variable light chain framework region LC-FR3 of Mab B variant 2 (v2)S3PAtorney Reference No. 2920951-538977GAGTKLELK Variable light chain framework region LC-FR4 of Mab B GAGTKLEIK Variable light chain framework region LC-FR4 of Mab B variant 2 (v2) L8I QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYGVS Variable heavy chain of WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLS Mab B ISRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPG YNLRGWFVYWGQGTLVIVS (Mab B HC) QVQLKESGPGLVQPSETLSLTCTVSGFSLTSYGVS Variable heavy chain of WVRQPPGKGLEWMGTMWNDGDTDYNSALRSKL Mab B variant 2 SISRDTSKSQVFLKMNSLQTEDTAIYYCARSQLPG YNLRGWFVYWGQGTLVIVS HC-FR1 Q16EHC-FR2 I13MHC-FR3 H2NHC-FR3 R8KHC-FR3 S15THC-FR3 L21FHC-FR3 M34IHC-FR3 F36Y(Mab B HC v2) ZVPMT’gTPSLLSASVGDRVTLNCKASHNINKNLE Variable light chain of Mab WYQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGT B DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL ELK (Mab B LC) DIQMTQSPPVLSASVGDRVTLSCKASHNINKNLE Variable light chain of Mab WYQQKLGEAPKLLIYYANNLQTGIPSRFSGSGSGT B variant 2 DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL EIK LC-FR1 V3QLC-FR1 T7SLC-FR1 S9PLC-FR1 L10VLC-FR1 N22SLC-FR3 S3PLC-FR4 L8I(Mab B LC v2) QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLS chain of Mab B and canine ISRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPG IgG-B YNLRGWFVYWGQGTLVIVSASTTAPSVFPLAPSC GSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGV (Chimeric B HC IgG-B)HTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAtorney Reference No. 2920951-538977AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDP EDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR WSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT QESLSHSPGKQVQLKESGPGLVQPSETLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWMGTMWNDGDTDYNSALRSKL chain of Mab B v2 and SISRDTSKSQVFLKMNSLQTEDTAIYYCARSQLPG canine IgG-B YNLRGWFVYWGQGTLVIVSAASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG HC-FR1 Q16E VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN HC-FR2 I13M VAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAP EMLGGPSVFIFPPKPKDTLLIARTPEVTCWVDLD HC-FR3 H2N PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR HC-FR3 R8K WSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI HC-FR3 S15T SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD HC-FR3 L21F FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY HC-FR3 M34I FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT HC-FR3 F36Y QESLSHSPGK(Chimeric B HC v2 IgG-B) D / FA / T’gT’PSLLSASVGDRVTLNCKASHNINKNLE Chimeric variable light WYQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGT chain of Mab B and canine DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL K light constant region ELKRNDAQPAVYLFQPSPDQLHTGSASWCLLNS FYPKDINVKWKVDGVIQDTGIQESVTEQDKDSTY(Chimeric B LC K) SLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQ RSECQRVD DIQMTQSPPVLSASVGDRVTLSCKASHNINKNLE Chimeric variable light WYQQKLGEAPKLLIYYANNLQTGIPSRFSGSGSGT chain of Mab B v2 and DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL canine K light constant EKRNDAQPAVYLFQPSPDQLHTGSASWCLLNSF region YPKDINVKWKVDGVIQDTGIQESVTEQDKDSTYS LSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQR SECQRVD LC-FR1 V3QLC-FR1 T7SLC-FR1 S9PLC-FR1 L10VLC-FR1 N22SLC-FR3 S3PLC-FR4 L8I (Chimeric B LC v2 K) MAVLGLLLCLVTFPSCVLSgKgZKE’SGPGLVQPSQ Chimeric variable heavy TLSLTCTVSGFSLTSYGVSWVRQPPGKGLEWIGT chain of Mab B and canine MWNDGDTDYHSALRSRLSISRDSSKSQVLLKMNS IgG-B with leader sequence LQTEDTAMYFCARSQLPGYNLRGWFVYWGQGTLVIVSASTTAPSVFPLAPSCGSTSGSTVALACLVSGYAtorney Reference No. 2920951-538977FPEPVTVSWNSGSLTSGVHTFPSVLQSSGLYSLSS (Canine chimeric B HC with MVTVPSSRWPSETFTCNVAHPASKTKVDKPVPKR leader) ENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDT LLIARTPEVTCVWDLDPEDPEVQISWFVDGKQM QTAKTQPREEQFNGTYRWSVLPIGHQDWLKGK QFTCKVNNKALPSPIERTISKARGQAHQPSVYVLP PSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQ EPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQR GDTFICAVMHEALHNHYTQESLSHSPGK MAVLGLLLCLVTFPSCVLSQVQLKESGPGLVQPSEChimeric variable heavy TLSLTCTVSGFSLTSYGVSWVRQPPGKGLEWMGT chain of Mab B v2 and MWNDGDTDYNSALRSKLSISRDTSKSQVFLKMNS canine IgG-B with leader LQTEDTAIYYCARSQLPGYNLRGWFVYWGQGTL sequence VIVSAASTTAPSVFPLAPSCGSTSGSTVALACLVSG YFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLYSLS SMVTVPSSRWPSETFTCNVAHPASKTKVDKPVPK HC-FR1 Q16E RENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKD HC-FR2 I13M TLLIARTPEVTCVWDLDPEDPEVQISWFVDGKQ HC-FR3 H2N MQTAKTQPREEQFNGTYRWSVLPIGHQDWLKG HC-FR3 R8K KQFTCKVNNKALPSPIERTISKARGQAHQPSVYVL HC-FR3 S15T PPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ HC-FR3 L21F QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ HC-FR3 M34I RGDTFICAVMHEALHNHYTQESLSHSPGK HC-FR3 F36Y(Canine chimeric B HC v2 IgG-B with leader) METDTLLLWVLLLWVPGSTGD / FA / T’gT’PSLLSAS Chimeric variable light VGDRVTLNCKASHNINKNLEWYQQKLGEAPKLLI chain of Mab B and canine YYANNLQTGISSRFSGSGSGTDYTLTISSLQPEDV K light constant region with ATYYCYQYNSGHTFGAGTKLELKRNDAQPAVYL leader sequence FQPSPDQLHTGSASWCLLNSFYPKDINVKWKVD GVIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLS HELYSCEITHKSLPSTLIKSFQRSECQRVD (Canine chimeric B LC K with leader) METDTLLLWVLLLWVPGSTGDIQMTQSPPVLSAS Chimeric variable light VGDRVTLSCKASHNINKNLEWYQQKLGEAPKLLI chain of Mab B v2 and YYANNLQTGIPSRFSGSGSGTDYTLTISSLQPEDV canine K light constant ATYYCYQYNSGHTFGAGTKLEIKRNDAQPAVYLF region with leader sequence QPSPDQLHTGSASWCLLNSFYPKDINVKWKVDG VIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLSH ELYSCEITHKSLPSTLIKSFQRSECQRVD LC-FR1 V3QLC-FR1 T7SLC-FR1 S9PLC-FR1 L10VLC-FR1 N22SLC-FR3 S3PLC-FR4 L8I(Canine chimeric B LC v2 Kwith leader)Atorney Reference No. 2920951-538977QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLS chain of Mab B and feline ISRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPG IgG-1 YNLRGWFVYWGQGTLVIVSASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG (Feline chimeric B HC IgG- VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTC NVAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPP 1) PEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGP DDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRV VSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISK AKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFH PPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFV YSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGKZ>7EM7’g77’SLLSASVGDRVTLNCKASHNINKNLE Chimeric variable light WYQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGT chain of Mab B and feline K DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL light constant region ELKRSDAQPSVFLFQPSLDELHTGSASIVCILNDFY PKEVNVKWKVDGWQNKGIQESTTEQNSKDSTY(Feline chimeric B LC K) SLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLVKS FNRSECQRED / JTWT’gT’PSLLSASVGDRVTLNCKASHNINKNLE Chimeric variable light WYQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGT chain of Mab B and feline K DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL light constant region with no ELKRSDAQPSVFLFQPSLDELHTGSASIVCILNDFY N-linked glycosylation site PKEVNVKWKVDGWQNKGIQESTTEQNSKDSTY SLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLVKS(Feline chimeric B LC FQRSECQRE Kaglycos) EVQLVESGGDLVKPGGTLRLSCTVSGFSLTSYGVS Caninized variable heavy WVRQSPGKGLEWIGTMWNDGDTDYHSAVKGQL chain of Mab B v3 SISRDTSKSQVFLQMNSLRAEDTAMYYCARSQLP GYNLRGWFVYWGQGTLVTVSS MAVLGLLLCLVTFPSCVLSEVQLVESGGDLVKPG Caninized variable heavy GTLRLSCTVSGFSLTSYGVSWVRQSPGKGLEWIG chain of Mab B v3 and TMWNDGDTDYHSAVKGQLSISRDTSKSQVFLQM canine IgG-B with leader NSLRAEDTAMYYCARSQLPGYNLRGWFVYWGQ sequence GTLVTVSSASTTAPSVFPLAPSCGSTSGSTVALAC LVSGYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGL(Caninized B HC v3 IgG-B YSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDK PVPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPP with leader) KPKDTLLIARTPEVTCVWDLDPEDPEVQISWFVD GKQMQTAKTQPREEQFNGTYRWSVLPIGHQDW LKGKQFTCKVNNKALPSPIERTISKARGQAHQPSV YVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSN GQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSR WQRGDTFICAVMHEALHNHYTQESLSHSPGK METDTLLLWVLLLWVPGSTGEIVLTQSPASLAVS Caninized variable light LGQRATISCKASHNINKNLEWYQQKPGQPPKLLIY chain of Mab B v3 and YANNLQTGVPARFSGSGSGTDYSLNIHPMEEDDT canine K light constant AMYYCYQYNSGHTFGGGTKLEIKRNDAQPAVYL region with leader sequenceFQPSPDQLHTGSASWCLLNSFYPKDINVKWKVDAttorney Reference No. 2920951-538977GVIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLS HELYSCEITHKSLPSTLIKSFQRSECQRVD (Caninized B LC K with leader) EVQLVESGGDLVKPGGTLRLSCTVSGFSLTSYGVS Caninized variable heavy WVRQSPGKGLEWIGTMWNDGDTDYHSAVKGQL chain of Mab B v3 and SISRDTSKSQVFLQMNSLRAEDTAMYYCARSQLP canine IgG-B GYNLRGWFVYWGQGTLVTVSSASTTAPSVFPLAP SCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTS (Caninized B HC v3 IgG-B) GVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTC NVAHPASKTKVDKPVPKRENGRVPRPPDCPKCPA PEMLGGPSVFIFPPKPKDTLLIARTPEVTCWVDL DPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTY RWSVLPIGHQDWLKGKQFTCKVNNKALPSPIER TISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIK DFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGS YFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK EIVLTQSPASLAVSLGQRATISCKASHNINKNLEW Caninized variable light YQQKPGQPPKLLIYYANNLQTGVPARFSGSGSGT chain of Mab B v3 DYSLNIHPMEEDDTAMYYCYQYNSGHTFGGGTK LEIK EIVLTQSPASLAVSLGQRATISCKASHNINKNLEW Caninized variable light YQQKPGQPPKLLIYYANNLQTGVPARFSGSGSGT chain of Mab B v3 and DYSLNIHPMEEDDTAMYYCYQYNSGHTFGGGTK canine K light constant LEKRNDAQPAVYLFQPSPDQLHTGSASWCLLNS region FYPKDINVKWKVDGVIQDTGIQESVTEQDKDSTY SLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQ RSECQRVD (Caninized B LC v3 K) GPGLVQPSQTLSLTCTVSGFSLSSYHVHWVRQPP Mab E variable HC GKGLEWLGVMWNDGDTSYNLALNSRLSISRDTS KSQVFFKMSSLQTEDTATYYCARPELPGLTYGVW FPYWGQGTLVTVS ASMSISVGDRVTMNCKASQNVDSNVDWYQQKT Mab E variable LC GQSPNLLIYKASNRNTGVPDRFTGSGSGTDFTFTIS NMQAEDLAVYYCMQSTSYPLTFGSGTKLEIKRA GPGLVQPSQTLSLTCTVSGFSLTSYGVSWVRQPPG Mab F variable HC KGLEWIGTMWNDGDTDYHSALRSRLSISRDSSKS QVLLKMNSLQTEDTAMYFCARSQLPGYNLRGWF VYWGQGTLVIVS SLLSASVGDRVTLNCKASHNINKNLEWYQQKLGE Mab F variable LC APKLLIYYANNLQTGISSRFSGSGSGTDYTLTISSL QPEDVATYYCYQYNSGHTFGAGTKLELKRA MWQLVSSTALLLLVSAGTQAADVPKAVVVLEPK Exemplary canine CD16WNRVLTMDSVTLKCQGDHLLRDNYTWLHNGRPI with linker, and poly-His SNQISTYIIKNASIKNSGEYRCQTDQSKLSDPVQLE VHTGWLLLQVPRLVFQEGELIQLKCHSWKNTPVRNVQYFQNGRGKKFFYNNSEYHIPAATSEHNGSYFAttorney Reference No. 2920951-538977CRGIIGKKNESSEAVNIIIQGSSLPSTSLLLSHWPQG SGSHHHHHH PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWD Exemplary wild-type canine LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT IgG-B Fc YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGK PAPEMLGGPDVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPI ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10D PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPI ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10E PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWD Exemplary variant canine LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT IgG-B Fc YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPDE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI CD 16 enhancing binding KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDmutant GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGKI103D PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWD Exemplary variant canine LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT IgG-B Fc YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPEE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI CD 16 enhancing binding KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDmutant GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGKI103E PAPEMLGGPDVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPD ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10DI103DAttorney Reference No. 2920951-53897797 PAPEMLGGPDVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPE ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDE mutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10DI103E98 PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPD ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDE mutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10EI103D99 PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPE ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDE mutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10EI103EDESCRIPTION OF CERTAIN EMBODIMENTS

[0106] Compositions comprising antibodies that bind to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) are provided. In addition, antibodies, heavy chains, and light chains comprising one or more complementary determining regions (CDRs) are provided. Polynucleotides encoding antibodies to CPV and / or FPV are provided. Methods of producing or purifying antibodies to CPV and / or FPV are also provided. Methods of providing passive immunity against infection with a canine or feline parvovirus and / or treatment of parvoviral infection using compositions comprising antibodies to CPV and / or FPV are provided.

[0107] As used herein, numerical terms such as Kd are calculated based upon scientific measurements and, thus, are subject to appropriate measurement error. In some instances, a numerical term may include numerical values that are rounded to the nearest significant figure.

[0108] As used herein, “a” or “an” means “at least one” or “one or more” unless otherwise specified. As used herein, the term “or” means “and / or” unless specified otherwise.Attorney Reference No. 2920951-538977In the context of a multiple dependent claim, the use of “or” when referring back to other claims refers to those claims in the alternative only.Exemplary Parvovirus Antibodies

[0109] Antibodies directed against parvovirus are provided, for example antibodies that bind to CPV and / or FPV. Parvovirus antibodies provided herein include, but are not limited to, monoclonal antibodies, chimeric antibodies, caninized antibodies, and felinized antibodies.

[0110] Also provided herein are amino acid sequences of monoclonal parvovirus antibodies. For example, variable heavy chain CDRs (SEQ ID NOs: 4-6), variable light chain CDRs (SEQ ID NOs: 13-15), variable region heavy chain framework sequences (SEQ ID NOs: 7 and 9-11), and variable region light chain framework sequences (SEQ ID NOs: 16-19) for Mab A are provided. Also provided are variable heavy chain CDRs (SEQ ID NOs: 42-44), variable light chain CDRs (SEQ ID NOs: 52-54), variable region heavy chain framework sequences (SEQ ID NOs: 45, 47, 49, and 51), and variable region light chain framework sequences (SEQ ID NOs: 55, 57, 58, and 60) for Mab B. The amino acid sequences of the variable heavy chain and variable light chain of Mab A are provided (SEQ ID NOs: 20 and 22, respectively). Amino acid sequences of the variable heavy chain and variable light chain of Mab B are provided (SEQ ID NOs: 62 and 64, respectively).

[0111] In addition, the amino acid sequences of the CDRs, framework sequences, variable heavy and light chains of variant Mab A and Mab B antibodies are provided. In an aspects, the variable heavy chain CDRs (SEQ ID NOs 4-6), variable heavy chain framework regions (SEQ ID NOs: 8-10, and 12), the variable heavy chain (SEQ ID NO: 21), the variable light chain CDRs (SEQ ID NOs: 13-15), the variable light chain framework regions (SEQ ID NOSs: 16-19), and the variable light chain (SEQ ID NO: 22) of Mab A variant 2 (v2) are provided. The variable heavy chain CDRs (SEQ ID NOs 42-44), variable heavy chain framework regions (SEQ ID NOs: 46, 48, 50, and 51), the variable heavy chain (SEQ ID NO: 63), the variable light chain CDRs (SEQ ID NOs: 52-54), the variable light chain framework regions (SEQ ID NOSs: 56, 57, 59, and 61), and the variable light chain (SEQ ID NO: 65) of Mab B variant 2 (v2) are provided.

[0112] Also provided herein are chimeric canine, chimeric feline, caninized, and felinized antibodies derived from Mab A, Mab B, Mab A v2, and Mab B v2. In some embodiments, amino acid sequences of caninized and felinized Mab A, Mab B, Mab A v2, and Mab B v2 are provided, such as SEQ ID NOs: 34-41, 88, 77-80, 88, and 89. In some embodiments,Attorney Reference No. 2920951-538977amino acid sequences of chimeric antibodies derived from Mab A, Mab B, Mab A v2, and Mab B v2 are provided, such as SEQ ID NOs: 23-25, 28-33, and 66-76.

[0113] The term “antibody” herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (for example, bispecific (such as Bi-specific T-cell engagers) and trispecific antibodies), and antibody fragments (such as Fab, F(ab’)2, ScFv, minibody, diabody, triabody, and tetrabody) so long as they exhibit the desired antigenbinding activity. Canine, feline, and equine species have different varieties (classes) of antibodies that are shared by many mammalians.

[0114] The term antibody includes, but is not limited to, fragments that are capable of binding to an antigen, such as Fv, single-chain Fv (scFv), Fab, Fab’, di-scFv, sdAb (single domain antibody) and (Fab’)2 (including a chemically linked F(ab’)2). Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab’)2 fragment that has two antigen combining sites and is still capable of cross-linking antigen. The term antibody also includes, but is not limited to, chimeric antibodies, humanized antibodies, and antibodies of various species such as mouse, human, cynomolgus monkey, canine, feline, equine, etc. Furthermore, for all antibody constructs provided herein, variants having the sequences from other organisms are also contemplated. Thus, if a murine version of an antibody is disclosed, one of skill in the art will appreciate how to transform the murine sequence based antibody into a cat, dog, horse, etc. sequence. Antibody fragments also include either orientation of single chain scFvs, tandem di-scFv, diabodies, tandem tri-sdcFv, minibodies, etc. Antibody fragments also include nanobodies (sdAb, an antibody having a single, monomeric domain, such as a pair of variable domains of heavy chains, without a light chain). An antibody fragment can be referred to as being a specific species in some embodiments (for example, mouse scFv or a canine scFv). This denotes the sequences of at least part of the non-CDR regions, rather than the source of the construct. In some embodiments, the antibodies comprise a label or are conjugated to a second moiety.

[0115] The terms “label” and “detectable label” mean a moiety attached to an antibody or its analyte to render a reaction (for example, binding) between the members of the specific binding pair, detectable. The labeled member of the specific binding pair is referred to as “detectably labeled.” Thus, the term “labeled binding protein” refers to a protein with a label incorporated that provides for the identification of the binding protein. In some embodiments,Attorney Reference No. 2920951-538977the label is a detectable marker that can produce a signal that is detectable by visual or instrumental means, for example, incorporation of a radiolabeled amino acid or attachment to a polypeptide of biotinyl moieties that can be detected by marked avidin (for example, streptavidin containing a fluorescent marker or enzymatic activity that can be detected by optical or colorimetric methods). Examples of labels for polypeptides include, but are not limited to, the following: radioisotopes or radionuclides (for example,3H,14C,35S,90Y,99Tc,111In,125I,131I,177Lu,166Ho, or153Sm); chromogens, fluorescent labels (for example, FITC, rhodamine, lanthanide phosphors), enzymatic labels (for example, horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; predetermined polypeptide epitopes recognized by a secondary reporter (for example, leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags); and magnetic agents, such as gadolinium chelates. Representative examples of labels commonly employed for immunoassays include moieties that produce light, for example, acridinium compounds, and moieties that produce fluorescence, for example, fluorescein. In this regard, the moiety itself may not be detectably labeled but may become detectable upon reaction with yet another moiety.

[0116] The term “monoclonal antibody” refers to an antibody of a substantially homogeneous population of antibodies, that is, the individual antibodies comprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. Thus, a sample of monoclonal antibodies can bind to the same epitope on the antigen. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies may be made by the hybridoma method first described by Kohler and Milstein, 1975, Nature 256:495, or may be made by recombinant DNA methods such as described in U. S. Pat. No. 4,816,567. The monoclonal antibodies may also be isolated from phage libraries generated using the techniques described in McCafferty et al., 1990, Nature 348:552-554, for example, the content of each of these references are herein incorporated by reference in their entireties.

[0117] In some embodiments, the monoclonal antibody is a Mab A, Mab A v2, Mab B, or Mab B v2.Attorney Reference No. 2920951-538977

[0118] “Amino acid sequence,” means a sequence of amino acids residues in a peptide or protein. The terms “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues, and are not limited to a minimum length. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are encompassed by the definition. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. Furthermore, for purposes of the present disclosure, a “polypeptide” refers to a protein which includes modifications, such as deletions, additions, and substitutions (generally conservative in nature), to the native sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the proteins or errors due to PCR amplification.

[0119] “Parvovirus” as used herein refers to any naturally occurring parvovirus or parvovirus variant, and includes canine parvovirus (CPV), such as CPV-2a, CPV-2b, and CPV-2c, and feline parvovirus (feline panleukopenia virus, FPV).

[0120] As used herein, the term “epitope” refers to a site on a target molecule (for example, an antigen, such as a protein, nucleic acid, carbohydrate or lipid) to which an antigen-binding molecule (for example, an antibody, antibody fragment, or scaffold protein containing antibody binding regions) binds. Epitopes often include a chemically active surface grouping of molecules such as amino acids, polypeptides or sugar side chains and have specific three dimensional structural characteristics as well as specific charge characteristics. Epitopes can be formed both from contiguous or juxtaposed noncontiguous residues (for example, amino acids, nucleotides, sugars, lipid moiety) of the target molecule. Epitopes formed from contiguous residues (for example, amino acids, nucleotides, sugars, lipid moiety) typically are retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding typically are lost on treatment with denaturing solvents. An epitope may include but is not limited to at least 3, at least 5 or 8-10 residues (for example, amino acids or nucleotides). In some examples an epitope is less than 20 residues (for example, amino acids or nucleotides) in length, less than 15 residues or less than 12 residues. Two antibodies may bind the same epitope within an antigen if they exhibit competitive binding for the antigen. In some embodiments, an epitope can be identified by a certain minimal distance to a CDR residue on the antigen-binding molecule. In some embodiments, an epitope can be identified by the above distance, and further limited to those residuesAttorney Reference No. 2920951-538977involved in a bond (for example, a hydrogen bond) between an antibody residue and an antigen residue. An epitope can be identified by various scans as well, for example an alanine or arginine scan can indicate one or more residues that the antigen-binding molecule can interact with. Unless explicitly denoted, a set of residues as an epitope does not exclude other residues from being part of the epitope for a particular antibody. Rather, the presence of such a set designates a minimal series (or set of species) of epitopes. Thus, in some embodiments, a set of residues identified as an epitope designates a minimal epitope of relevance for the antigen, rather than an exclusive list of residues for an epitope on an antigen.

[0121] In some embodiments, the epitope comprises or consists of one of the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and / or SEQ ID NO: 3.

[0122] The binding properties of an antibody may be determined by the sequence and structure of six loops called complementarity-determining regions (CDRs). Three CDRs are found on the light chain (CDR-L1, CDR-L2, and CDR-L3) and three on the heavy chain (CDR-H1, CDR-H2, and CDR-H3). Non-CDR-H3 (CDR-L1, CDR-L2, CDR-L3, CDR-H1, and CDR-H2) appear to form a relatively small number of shapes, referred to as canonical classes (Chothia C et al. JMB, 1987, 196:901-917; Al-Lazikani B et all., JMB, 1997, 273:927-948). A canonical class may describe a set of loops that assume similar conformations, with the conformation being determined by the number and identity of the residues that constitute the loop and some residues in the framework region adjacent to the loop. The theory of canonical classes may postulate that the class of a loop can be identified by the presence of a few “key” residues at particular positions. Thus, using canonical classes, it may be possible to predict the structure of a novel CDR, by classifying it using key features of its sequence.

[0123] The term “CDR” means a complementarity determining region, which are antibody loops that make up antigen binding site, as defined by at least one manner of identification to one of skill in the art. CDR types may have structurally similar loops of different lengths. In some embodiments, CDRs can be defined in accordance with any of the Chothia numbering scheme, which is based on the location of the structural loop regions, the Kabat numbering scheme, which is based on sequence variability, a combination of Kabat and Chothia, the AbM definition, the contact definition, which is based on an analysis of the available complex crystal structures, or a combination of the Kabat, Chothia, AbM, or contact definitions, for example, Table 2. The various CDRs within an antibody can be designated by their appropriate number and chain type, including, without limitation as CDR-H1, CDR-H2,Attorney Reference No. 2920951-538977CDR-H3, CDR-L1, CDR-L2, and CDR-L3. The term “CDR” is used herein to also encompass a “hypervariable region” or HVR, including hypervariable loops.

[0124] Table 2 shows CDR residues making contact in each antibody with summary data for each CDR. (novoprolabs.com / tools / cdr and bioinf.org.uk / abs / info.html)Table 2Loop Kabat AbM Chothia1Contact2IMGT CDR-L1 L24-L34 L24-L34 L24-L34 L30-L36 L27-L32 CDR-L2 L50-L56 L50-L56 L50-L56 L46-L55 L50-L51 CDR-L3 L89-L97 L89-L97 L89-L97 L89-L96 L89-L97 CDR-H1 H31-H35BH26—(Kabat H26-H35B H30-H35B H26-H35B H32..34Numbering)3CDR-H1 H31-H35(Chothia H26-H35 H26-H32 H30-H35 H26-H33 Numbering)CDR-H2 H50-H65 H50-H58 H52-H56 H47-H58 H51-H56 CDR-H3 H95-H102 H95-H102 H95-H102 H93-H101 H93-H102Note (1) some of these definitions (particularly for Chothia loops) vary depending on the individual publication examined.Note (2) any of the numbering schemes can be used for these CDR definitions, except the contact definition uses the Chothia or Martin (Enhanced Chothia) definition.Note (3) the end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop. (This is because the Kabat numbering scheme places the insertions at H35A and H35B.). If neither H35A nor H35B is present, the loop ends at H32; If only H35A is present, the loop ends at H33; If both H35A and H35B are present, the loop ends at H34.

[0125] In some embodiments, antibodies described herein comprises a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5; and / or (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, parvovirus antibodies described herein comprises a light chain comprising (a) a CDR-L1 comprising the amino acidAttorney Reference No. 2920951-538977sequence of SEQ ID NO: 13; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and / or (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0126] In embodiments, parvovirus antibodies described herein comprises each of a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6 and a light chain comprising (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0127] In some embodiments, parvovirus antibodies described herein comprises a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 42; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 43; and / or (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 44. In some embodiments, a parvovirus antibodies described herein comprises a light chain comprising (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and / or (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.

[0128] In some embodiments, parvovirus antibodies described herein comprises each of a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 42; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 43; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 44 and a light chain comprising (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.

[0129] In some embodiments, parvovirus antibodies described herein comprise a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H1 is substituted by a different amino acid; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H2 is substituted by a different amino acid; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H3 is substituted by a different amino acid and a light chain comprising (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L1 is substituted by a different amino acid; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14Attorney Reference No. 2920951-538977or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L2 is substituted by a different amino acid; and / or (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L3 is substituted by a different amino acid. In aspects, the amino acid substitution is a conservative substitution.

[0130] In some embodiments, parvovirus antibodies described herein comprise a heavy chain comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H1 is substituted by a different amino acid; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H2 is substituted by a different amino acid; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 44 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-H3 is substituted by a different amino acid and a light chain comprising (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L1 is substituted by a different amino acid; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L2 is substituted by a different amino acid; and / or (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof wherein 1, 2, or 3 amino acids of the CDR-L3 is substituted by a different amino acid. In aspects, the amino acid substitution is a conservative substitution.

[0131] The term “variable region” as used herein refers to a region comprising at least three CDRs. In some embodiments, the variable region includes the three CDRs and at least one framework region (“FR”). The terms “heavy chain variable region” or “variable heavy chain” are used interchangeably to refer to a region comprising at least three heavy chain CDRs. The terms “light chain variable region” or “variable light chain” are used interchangeably to refer to a region comprising at least three light chain CDRs. In some embodiments, the variable heavy chain or variable light chain comprises at least one framework region. In some embodiments, an antibody comprises at least one heavy chain framework region selected from HC-FR1, HC-FR2, HC-FR3, and HC-FR4. In some embodiments, an antibody comprises at least one light chain framework region selected from LC-FR1, LC-FR2, LC-FR3, and LC-FR4. The framework regions may be juxtaposed between light chain CDRs or between heavy chain CDRs. For example, an antibody may comprise a variable heavy chain having the following structure: (HC-FR1)-(CDR-H1)-(HC-FR2)-(CDR-H2)-(HC-FR3)-(CDR-H3)-(HC-FR4). An antibody may comprise a variable heavy chain having the following structure: (CDR-H1)-(HC-FR2)-(CDR-H2)-(HC-FR3)-Attorney Reference No. 2920951-538977(CDR-H3). An antibody may also comprise a variable light chain having the following structure: (LC-FR1)-(CDR-L1)-(LC-FR2)-(CDR-L2)-(LC-FR3)-(CDR-L3)-(LC-FR4). An antibody may also comprise a variable light chain having the following structure: (CDR-L1)-(LC-FR2)-(CDR-L2)-(LC-FR3)-(CDR-L3).

[0132] In some embodiments, parvovirus antibodies described herein comprise one or more of (a) a variable region heavy chain framework 1 (HC-FR1) sequence of SEQ ID NO: 7 or SEQ ID NO: 8, (b) a HC-FR2 sequence of SEQ ID NO: 9, (c) a HC-FR3 sequence of SEQ ID NO: 10, (d) a HC-FR4 sequence of SEQ ID NO: 11 or SEQ ID NO: 12, (e) a variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO: 16, (f) an LC-FR2 sequence of SEQ ID NO: 17, (g) an LC-FR3 sequence of SEQ ID NO: 18, or (h) an LC-FR4 sequence of SEQ ID NO: 19.

[0133] In some embodiments, parvovirus antibodies described herein comprise one or more of (a) a variable region heavy chain framework 1 (HC-FR1) sequence of SEQ ID NO: 45 or SEQ ID NO: 46, (b) a HC-FR2 sequence of SEQ ID NO: 47 or SEQ ID NO: 48, (c) a HC-FR3 sequence of SEQ ID NO: 49 or SEQ ID NO: 50, (d) a HC-FR4 sequence of SEQ ID NO: 51, (e) a variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO: 55 or SEQ ID NO: 56, (f) an LC-FR2 sequence of SEQ ID NO: 57, (g) an LC-FR3 sequence of SEQ ID NO: 58 or SEQ ID NO: 59, or (h) an LC-FR4 sequence of SEQ ID NO: 60.

[0134] In some embodiments, a parvovirus antibody comprises a variable light chain sequence of SEQ ID NO: 22, SEQ ID NO: 87, SEQ ID NO: 41, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 89, SEQ ID NO: 82, or SEQ ID NO: 84. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 40, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 88, SQ ID NO: 81, or SEQ ID NO: 83.

[0135] In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 20 and a variable light chain sequence of SEQ ID NO: 22. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 21 and a variable light chain sequence of SEQ ID NO: 22. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 85 and a variable light chain sequence of SEQ ID NO: 87. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 86 and a variable light chain sequence of SEQ ID NO: 87. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 40 and a variable light chain sequence of SEQ ID NO: 41. In some embodiments, a parvovirus antibody comprises a variable heavy chainAttorney Reference No. 2920951-538977sequence of SEQ ID NO: 62 and a variable light chain sequence of SEQ ID NO: 64 or SEQ ID NO: 65. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 63 and a variable light chain sequence of SEQ ID NO: 64 or SEQ ID NO: 65. In some embodiments, a parvovirus antibody comprises a variable heavy chain sequence of SEQ ID NO: 88 and a variable light chain sequence of SEQ ID NO: 89.

[0136] The term “constant region” as used herein refers to a region comprising at least three constant domains. The terms “heavy chain constant region” or “constant heavy chain” are used interchangeably to refer to a region comprising at least three heavy chain constant domains, CH1, CH2, and CH3. Nonlimiting exemplary heavy chain constant regions include γ, δ, α, ε, and μ. Each heavy chain constant region corresponds to an antibody isotype. For example, an antibody comprising a γ constant region is an IgG antibody, an antibody comprising a δ constant region is an IgD antibody, an antibody comprising an α constant region is an IgA antibody, an antibody comprising a μ constant region is an IgM antibody, and an antibody comprising an ε constant region is an IgE antibody. Certain isotypes can be further subdivided into subclasses. For example, IgG antibodies include, but are not limited to, IgG1 (comprising a γ1 constant region), IgG2 (comprising a γ2 constant region), IgG3 (comprising a γ3 constant region), and IgG4 (comprising a γ4 constant region) antibodies; IgA antibodies include, but are not limited to, IgA1 (comprising an α1 constant region) and IgA2 (comprising an α2 constant region) antibodies; and IgM antibodies include, but are not limited to IgMl and IgM2. The terms “light chain constant region” or “constant light chain” are used interchangeably to refer to a region comprising a light chain constant domain, CL.Nonlimiting exemplary light chain constant regions include λ and κ. Non-function-altering deletions and alterations within the domains are encompassed within the scope of the term “constant region” unless designated otherwise. Canine and feline have antibody classes such as IgG, IgA, IgD, IgE, and IgM. Within the canine IgG antibody class are IgG-A, IgG-B, IgG-C, and IgG-D. Within the feline IgG antibody class are IgGl, IgG2a, and IgG2b.

[0137] The term “chimeric antibody” or “chimeric” refers to an antibody in which a portion of the heavy chain or light chain is derived from a particular source or species, while at least a part of the remainder of the heavy chain or light chain is derived from a different source or species. In some embodiments, a chimeric antibody refers to an antibody comprising at least one variable region from a first species (such as mouse, rat, cynomolgus monkey, etc.) and at least one constant region from a second species (such as human, dog, cat, equine, etc.). In some embodiments, a chimeric antibody comprises at least one mouse variable region and at least one canine constant region. In some embodiments, a chimericAttorney Reference No. 2920951-538977antibody comprises at least one mouse variable region and at least one feline constant region. In some embodiments, all of the variable regions of a chimeric antibody are from a first species and all of the constant regions of the chimeric antibody are from a second species. In some embodiments, a chimeric antibody comprises a constant heavy chain region or constant light chain region from a companion animal. In some embodiments, a chimeric antibody comprises a mouse variable heavy and light chains and a companion animal constant heavy and light chains. For example, a chimeric antibody may comprise a mouse variable heavy and light chains and a canine constant heavy and light chains; a chimeric antibody may comprise a mouse variable heavy and light chains and a feline constant heavy and light chains; or a chimeric antibody may comprise a mouse variable heavy and light chains and an equine constant heavy and light chains.

[0138] In some embodiments, the disclosure provides for parvovirus antibodies and compositions comprising a chimeric antibody comprising: (a) (i) a heavy chain amino acid sequence of SEQ ID NO: 23; (ii) a light chain amino acid sequence of SEQ ID NO: 25; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (b) (i) a heavy chain amino acid sequence of SEQ ID NO: 24; (ii) a light chain amino acid sequence of SEQ ID NO: 25; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (c) (i) a heavy chain amino acid sequence of SEQ ID NO: 31; (ii) a light chain amino acid sequence of SEQ ID NO: 32; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (d) (i) a heavy chain amino acid sequence of SEQ ID NO: 31; (ii) a light chain amino acid sequence of SEQ ID NO: 33; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (e) (i) a heavy chain amino acid sequence of SEQ ID NO: 66; (ii) a light chain amino acid sequence of SEQ ID NO: 68; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (f) (i) a heavy chain amino acid sequence of SEQ ID NO: 67; (ii) a light chain amino acid sequence of SEQ ID NO: 69; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (g) (i) a heavy chain amino acid sequence of SEQ ID NO: 74; (ii) a light chain amino acid sequence of SEQ ID NO: 75; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); or (h) (i) a heavy chain amino acid sequence of SEQ ID NO: 74; (ii) a light chain amino acid sequence of SEQ ID NO: 75; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii).

[0139] In other embodiments, the disclosure provides for chimeric antibodies comprising: (a) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 23; (ii) a light chainAttorney Reference No. 2920951-538977amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 25; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (b) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 24; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 25; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (c) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 31; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 32; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (d) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 31; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 33; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (e) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 66; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 68; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (f) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 67; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 69; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); (g) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 74; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 75; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii); or (h) (i) a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 74; (ii) a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 75; or (iii) a heavy chain amino acid sequence as in (i) and a light chain sequence as in (ii).Attorney Reference No. 2920951-538977

[0140] In some embodiments, parvovirus antibodies described herein comprise a heavy chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 24 and a light chain amino acid sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 25. In other embodiments, parvovirus antibodies described herein comprise a heavy chain amino acid sequence of SEQ ID NO: 24 and a light chain amino acid sequence of SEQ ID NO: 25, wherein in aspects SEQ ID NO: 24 and / or SEQ ID NO: 25 comprise at most one, two, three, four, five, ten, or twenty amino acid substitutions. In an aspect, one or more of the amino acid substitutions are conservative substitutions.

[0141] A “canine chimeric,” “chimeric canine,” or “canine chimeric antibody” refers to a chimeric antibody having at least a portion of a heavy chain or a portion of a light chain derived from a dog. A “feline chimeric,” “chimeric feline,” or “feline chimeric antibody” refers to a chimeric antibody having at least a portion of a heavy chain or a portion of a light chain derived from a cat. In some embodiments, a canine chimeric antibody comprises a mouse or rat variable heavy and light chains and a canine constant heavy and light chains. In some embodiments, a feline chimeric antibody comprises a mouse or rat variable heavy and light chains and a feline constant heavy and light chains.

[0142] In some embodiments, a parvovirus antibody comprises a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region.

[0143] In some embodiments, a parvovirus antibody comprises a feline heavy chain constant region selected from an IgGl, IgG2a, and IgG2b constant region.

[0144] A “caninized antibody” means an antibody in which at least one amino acid in a portion of a non-canine variable region has been replaced with the corresponding amino acid from a canine variable region. In some embodiments, a caninized antibody comprises at least one canine constant region (e.g., a γ constant region, an α constant region, a δ constant region, an ε constant region, a μ constant region, or etc.) or fragment thereof. In some embodiments, a caninized antibody is an antibody fragment, such as Fab, scFv, (Fab’)2, etc. The term “caninized” also denotes forms of non-canine (for example, murine) antibodies that are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other antigen-binding sequences of antibodies) that contain minimal sequence of non-canine immunoglobulin. Caninized antibodies can include canine immunoglobulins (recipient antibody) in which residues from a CDR of the recipient are substituted by residues from a CDR of a non-canine species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some instances, FvAttorney Reference No. 2920951-538977framework region (FR) residues of the canine immunoglobulin are replaced by corresponding non-canine residues. Furthermore, the caninized antibody can comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance.

[0145] In some embodiments, at least one amino acid residue in a portion of a rat or a mouse variable heavy chain or a rat or a mouse variable light chain has been replaced with the corresponding amino acid from a canine variable region. In some embodiments, the modified chain is fused to a canine constant heavy chain or a canine constant light chain.

[0146] A “felinized antibody” means an antibody in which at least one amino acid in a portion of a non-feline variable region has been replaced with the corresponding amino acid from a feline variable region. In some embodiments, a felinized antibody comprises at least one feline constant region (e.g., a γ constant region, an α constant region, a δ constant region, an ε constant region, a μ constant region, or etc.) or fragment thereof. In some embodiments, a felinized antibody is an antibody fragment, such as Fab, scFv, (Fab’)2, etc. The term “felinized” also denotes forms of non-feline (for example, murine) antibodies that are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other antigen-binding sequences of antibodies) that contain minimal sequence of non-feline immunoglobulin. Felinized antibodies can include feline immunoglobulins (recipient antibody) in which residues from a CDR of the recipient are substituted by residues from a CDR of a non-feline species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the feline immunoglobulin are replaced by corresponding non-feline residues. Furthermore, the felinized antibody can comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance.

[0147] In some embodiments, at least one amino acid residue in a portion of a mouse variable heavy chain or a mouse variable light chain has been replaced with the corresponding amino acid from a feline variable region. In some embodiments, the modified chain is fused to a feline constant heavy chain or a canine constant light chain.

[0148] A “fragment crystallizable polypeptide” or “Fc polypeptide” is the portion of an antibody molecule that interacts with effector molecules and cells. It comprises theC-terminal portions of the immunoglobulin heavy chains. As used herein, an Fc polypeptide includes fragments of the Fc domain having one or more biological activities of an entire Fc polypeptide. An “effector function” of the Fc polypeptide is an action or activity performedAttorney Reference No. 2920951-538977in whole or in part by any antibody in response to a stimulus and may include complement fixation and / or ADCC (antibody-dependent cellular cytotoxicity) induction and / or ADCP (antibody-dependent cellular phagocytosis).

[0149] In some embodiments, a biological activity of an Fc polypeptide is the ability to bind FcRn. In some embodiments, a biological activity of an Fc polypeptide is the ability to bind Clq. In some embodiments, a biological activity of an Fc polypeptide is the ability to bind CD16. In some embodiments, a biological activity of an Fc polypeptide is the ability to bind protein A.

[0150] The term “IgX Fc” means the Fc region is derived from a particular antibody isotype (e.g., IgG, IgA, IgD, IgE, IgM, etc.), where “X” denotes the antibody isotype. Thus, “IgG Fc” denotes the Fc region of a y chain, “IgA Fc” denotes the Fc region of an a chain, “IgD Fc” denotes the Fc region of a 3 chain, “IgE Fc” denotes the Fc region of an E chain, “IgM Fc” denotes the Fc region of a p. chain, etc. In some embodiments, the IgG Fc region comprises CH1, hinge, CH2, CH3, and CL1. “IgX-N-Fc” denotes that the Fc region is derived from a particular subclass of antibody isotype (such as canine IgG subclass A, B, C, or D; or feline IgG subclass 1, 2a, or 2b), where “N” denotes the subclass. In some embodiments, IgX Fc or IgX-N-Fc regions are derived from a companion animal, such as a dog or a cat. In some embodiments, IgG Fc regions are isolated from canine γ heavy chains, such as IgG-A, IgG-B, IgG-C, or IgG-D. In some instances, IgG Fc regions are isolated from feline γ heavy chains, such as IgGl, IgG2a, or IgG2b. Antibodies comprising an Fc region of IgG-A, IgG-B, IgG-C, or IgG-D may provide for higher expression levels in recombination production systems.

[0151] The terms “IgX Fc” and “IgX Fc polypeptide” include wild-type IgX Fc polypeptides and variant IgX Fc polypeptides, unless indicated otherwise.

[0152] In some embodiments, a variant IgG Fc polypeptide comprises a variant IgG Fc polypeptide of a companion animal species. In some embodiments, a variant IgG Fc polypeptide comprises a variant canine IgG Fc polypeptide or a feline IgG Fc polypeptide. In some embodiments, a variant IgG Fc polypeptide (e.g., a variant canine IgG-A Fc polypeptide, a variant canine IgG-C Fc polypeptide, or a variant canine IgG-D Fc polypeptide, variant feline IgGla Fc polypeptide, variant feline IgGlb Fc polypeptide, or variant feline IgG2 Fc polypeptide) has an activity that the reference (e.g., wild-type) polypeptide substantially lacks.

[0153] An antibody may be modified to extend or shorten its half-life. In some embodiments involving a higher dose of antibody, a shorter half-life may be desirable forAttorney Reference No. 2920951-538977acute treatment. In some embodiments involving a lower dose of antibody, a longer half-life may be desirable for prolonged treatment. For example, as discussed below, mutations in IgG Fc that affect FcRn interactions may be introduced.

[0154] In some embodiments, a parvovirus antibody comprises a wild-type or variant IgG Fc having complement fixation activity (or complement-dependent cytotoxicity (CDC)). In some embodiments, a parvovirus antibody comprises a wild-type or variant IgG Fc having antibody-dependent cellular cytotoxicity (ADCC) activity. In some embodiments, a parvovirus antibody comprises a wild-type or variant IgG Fc having antibody-dependent cellular phagocytosis (ADCP) activity. In some embodiments, a parvovirus antibody comprises a wild-type or variant IgG Fc having complement fixation activity and / or ADCC activity and / or ADCP activity. IgG Fc polypeptides may be modified to have an effector function or to have an enhanced effector function.

[0155] In some embodiments, a parvovirus antibody comprises a wild-type or variant IgG Fc the binds to canine FcRn at low pH. In some embodiments, a parvovirus comprises a wildtype or variant IgG Fc that binds to Clq. In some embodiments, a parvovirus comprises a wild-type or variant IgG Fc that binds to CD16. In some embodiments, a parvovirus comprises a variant IgG Fc comprising one or more afucosylated glycan.

[0156] In some embodiments, a variant IgG Fc (e.g., a variant canine IgG Fc polypeptide or a variant feline IgG Fc polypeptide) has modified FcRn binding affinity compared to a reference polypeptide. In some embodiments, a variant IgG Fc has increased FcRn binding affinity at an acidic pH (e.g., at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5) compared to a reference polypeptide. Exemplary variant IgG Fc polypeptides having increased FcRn binding affinity are disclosed in WO 2020 / 082048, which is incorporated by reference herein in its entirety.

[0157] In some embodiments, a variant IgG Fc (e.g., a variant canine IgG Fc polypeptide or a variant feline IgG Fc polypeptide) has modified Clq binding affinity compared to a reference polypeptide. In some embodiments, a variant IgG Fc has increased Clq binding affinity compared to a reference polypeptide. Exemplary variant IgG Fc polypeptides having increased Clq binding affinity are disclosed in WO 2020 / 139984 (e.g., Example 2), which is incorporated by reference herein in its entirety.

[0158] In some embodiments, a variant IgG Fc (e.g., a variant canine IgG Fc polypeptide or a variant feline IgG Fc polypeptide) has modified CD 16 binding affinity compared to a reference polypeptide. In some embodiments, a variant IgG Fc has increased CD16 bindingAttorney Reference No. 2920951-538977affinity compared to a reference polypeptide. Exemplary variant IgG Fc polypeptides having increased CD16 binding affinity are disclosed in US 2022 / 0267414A1(e.g., Example 2), which is incorporated by reference herein in its entirety.

[0159] In some embodiments, a variant canine IgG Fc has enhanced CD 16 binding affinity compared to a reference polypeptide. In some embodiments a variant IgG Fc comprises a) an aspartic acid or a glutamic acid at a position corresponding to position 10 of SEQ ID NO: 91; b)an aspartic acid or a glutamic acid at position 10 of SEQ ID NO: 91; c) an aspartic acid or a glutamic acid at a position corresponding to position 103 of SEQ ID NO: 91; d) an aspartic acid or a glutamic acid at position 103 of SEQ ID NO: 91; e) an aspartic acid or a glutamic acid at a position corresponding to position 10 and / or position 103 of SEQ ID NO: 91; f) an aspartic acid or a glutamic acid at position 10 and / or position 103 of SEQ ID NO: 91. In some embodiments a variant IgG Fc comprises the amino acid sequence of SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, or SEQ ID NO: 99.

[0160] In some embodiments, a variant IgG Fc (e.g., a variant canine IgG Fc polypeptide or a variant feline IgG Fc polypeptide) has modified Protein A binding affinity compared to a reference polypeptide. In some embodiments, a variant IgG Fc has increased Protein A binding affinity compared to a reference polypeptide. Exemplary variant IgG Fc polypeptides having increased Protein A binding affinity are disclosed in WO 2020 / 139984 (e.g., Example 2), which is incorporated by reference herein in its entirety.

[0161] The term “affinity” means the strength of the sum total of noncovalent interactions between a single binding site of a molecule (for example, an antibody) and its binding partner (for example, an antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, such as, for example, immunoblot, ELISA KD, KinExA, biolayer interferometry (BLI), or surface plasmon resonance devices.

[0162] The terms “KD,” “Kd,” “Kd” or “Kd value” as used interchangeably to refer to the equilibrium dissociation constant of an antibody-antigen interaction. In some embodiments, the Kdof the antibody is measured by using biolayer interferometry assays using a biosensor, such as an Octet® System (Pall ForteBio LLC, Fremont, CA) according to the supplier’s instructions. Briefly, biotinylated antigen is bound to the sensor tip and the association of antibody is monitored for ninety seconds and the dissociation is monitored for 600 seconds. The buffer for dilutions and binding steps is 20 mM phosphate, 150 mM NaCl, pH 7.2. A buffer only blank curve is subtracted to correct for any drift. The data are fit to a 2:1 bindingAttorney Reference No. 2920951-538977model using ForteBio data analysis software to determine association rate constant (kon), dissociation rate constant (koff), and the Kd. The equilibrium dissociation constant (Kd) is calculated as the ratio of koff / kon. The term “kon” refers to the rate constant for association of an antibody to an antigen and the term “koff” refers to the rate constant for dissociation of an antibody from the antibody / antigen complex.

[0163] The term “binds” to an antigen or epitope is a term that is well understood in the art, and methods to determine such binding are also well known in the art. A molecule is said to exhibit “binding” if it reacts, associates with, or has affinity for a particular cell or substance and the reaction, association, or affinity is detectable by one or more methods known in the art, such as, for example, immunoblot, ELISA KD, KinExA, biolayer interferometry (BLI), surface plasmon resonance devices, or etc.

[0164] “Surface plasmon resonance” denotes an optical phenomenon that allows for the analysis of real-time biospecific interactions by detection of alterations in protein concentrations within a biosensor matrix, for example using the BIAcore™ system (BIAcore International AB, a GE Healthcare company, Uppsala, Sweden and Piscataway, N. J.). For further descriptions, see Jonsson et al. (1993) Ann. Biol. Clin. 51: 19-26, the contents of which is herein incorporated by reference.

[0165] “Biolayer interferometry” refers to an optical analytical technique that analyzes the interference pattern of light reflected from a layer of immobilized protein on a biosensor tip and an internal reference layer. Changes in the number of molecules bound to the biosensor tip cause shifts in the interference pattern that can be measured in real-time. A nonlimiting exemplary device for biolayer interferometry is an Octet® system (Pall ForteBio LLC). See, e.g., Abdiche et al., 2008, Anal. Biochem. 377: 209-277.

[0166] In some embodiments, a parvovirus antibody binds to a canine parvovirus or a feline parvovirus with a dissociation constant (Kd) of less than 5 x 10'6M, less than 1 x 10"6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10'8M, less than 1 x 10'8M, less than 5 x 10'9M, less than 1 x 10'9M, less than 5 x 10’10M, less than 1 x 10'10M, less than 5 x 10'11M, less than 1 x 10'11M, less than 5 x 10'12M, or less than 1 x 10'12M, as measured by biolayer interferometry. In some embodiments, a parvovirus antibody binds to a canine parvovirus or a feline parvovirus with a Kd of between 5 x 10'6M and 1 x 10'6M, between 5 x 10'6M and 5 x 10'7M, between 5 x 10'6M and 1 x 10'7M, between 5 x 10'6M and 5 x 10'8M, between 5 x 10'6M and 1 x 10'8M, between 5 x 10’6M and 5 x 10’9M, between 5 x 10'6M and 1 x 10"9M, between 5 x 10'6M and 5 x 10’10M, between 5 x 10'6M and 1 x 10'10M, between 5 x 10"6M and 5 x 10"11M, between 5 x 10'6M and 1 x 10"11M, between 5 x 10'6MAttorney Reference No. 2920951-538977and 5 x IO’12M, between 5 x 10'6M and 1 x IO’12M, between 1 x 10'6M and 5 x 10’7M, between 1 x 10‘6M and 1 x 10‘7M, between 1 x 10‘6M and 5 x IO"8M, between 1 x 10‘6M and 1 x IO’8M, between 1 x 10'6M and 5 x 10'9M, between 1 x 10'6M and 1 x 10'9M, between 1 x 10'6M and 5 x 10'10M, between 1 x 10'6M and 1 x 10'10M, between 1 x 10'6M and 5 x IO’11M, between 1 x 10'6M and 1 x IO’11M, between 1 x 10'6M and 5 x 10’12M, between 1 x 10'6M and 1 x 10'12M, between 5 x 10'7M and 1 x 10'7M, between 5 x 10'7M and 5 x IO’8M, between 5 x 10'7M and 1 x 10"8M, between 5 x 10'7M and 5 x 10'9M, between 5 x 10"7M and 1 x 10"9M, between 5 x 10’7M and 5 x IO'10M, between 5 x 10'7M and 1 x IO’10M, between 5 x 10'7M and 5 x IO’11M, between 5 x 10'7M and 1 x IO’11M, between 5 x 10'7M and 5 x 10'12M, between 5 x 10'7M and 1 x 10'12M, between 1 x 10'7M and 5 x IO’8M, between 1 x 10’7M and 1 x 10"8M, between 1 x 10'7M and 5 x 10'9M, between 1 x 10"7M and 1 x 10"9M, between 1 x 10’7M and 5 x IO’10M, between 1 x 10'7M and 1 x 10'10M, between 1 x 10'7M and 5 x IO’11M, between 1 x 10'7M and 1 x IO’11M, between 1 x 10'7M and 5 x 10'12M, between 1 x 10'7M and 1 x 10'12M, between 5 x 10'8M and 1 x 10'8M, between 5 x 10‘8M and 5 x 10‘9M, between 5 x 10'8M and 1 x 10'9M, between 5 x 10"8M and 5 x IO"10M, between 5 x 10"8M and 1 x IO"10M, between 5 x 10"8M and 5 x IO'11M, between 5 x IO'8M and 1 x IO’11M, between 5 x IO'8M and 5 x 10’12M, between 5 x 10'8M and 1 x 10'12M, between 1 x 10'8M and 5 x 10'9M, between 1 x IO'8M and 1 x IO’9M, between 1 x 10'8M and 5 x 10'10M, between 1 x 10'8M and 1 x 10'10M, between 1 x 10"8M and 5 x IO"11M, between 1 x 10"8M and 1 x IO"11M, between 1 x 10"8M and 5 x 10’12M, between 1 x IO'8M and 1 x 10’12M, between 5 x 10'9M and 1 x 10’9M, between 5 x 10'9M and 5 x 10'10M, between 5 x 10'9M and 1 x 10'10M, between 5 x 10'9M and 5 x IO’11M, between 5 x 10'9M and 1 x IO’11M, between 5 x 10'9M and 5 x 10’12M, between 5 x 10"9M and 1 x 10"12M, between 1 x 10'9M and 5 x 10'10M, between 1 x 10"9M and 1 x IO’10M, between 1 x 10'9M and 5 x IO’11M, between 1 x 10'9M and 1 x IO’11M, between 1 x 10'9M and 5 x 10'12M, between 1 x 10'9M and 1 x 10'12M, between 5 x 10'10M and 1 x 10'10M, between 5 x IO'10M and 5 x IO’11M, between, between 1 x IO’10M and 5 x IO"11M, 1 x 10'10M and 1 x 10'11M, between 1 x 10'10M and 5 x 10'12M, between 1 x IO’10M and 1 x 10'12M, between 5 x 10'11M and 1 x 10'12M, between 5 x 10'11M and 5 x 10'12M, between 5 x 10'11M and 1 x 10'12M, between 1 x 10'11M and 5 x 10'12M, or between 1 x 10'11M and 1 x 10'12M, as measured by biolayer interferometry. In some embodiments, a parvovirus antibody binds to a canine parvovirus or a feline parvovirus, as determined by immunoblot analysis.Attorney Reference No. 2920951-538977

[0167] “Wild-type” refers to a non-mutated version of a polypeptide that occurs in nature, or a fragment thereof. A wild-type polypeptide may be produced recombinantly.

[0168] A “variant” means a biologically active polypeptide having at least about 50% amino acid sequence identity with the native sequence polypeptide after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Such variants include, for instance, polypeptides wherein one or more amino acid residues are added, deleted, at the N- or C-terminus of the polypeptide.

[0169] In some embodiments, a variant has at least 1, 2, 3, 4, or 5 amino acids substituted by a different amino acid.

[0170] In some embodiments, a variant has at least about 50% sequence identity with the reference nucleic acid molecule or polypeptide after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Such variants include, for instance, polypeptides wherein one or more amino acid residues are added, deleted, at the N-or C-terminus of the polypeptide. In some embodiments, a variant has at least about 50% sequence identity, at least about 60% sequence identity, at least about 65% sequence identity, at least about 70% sequence identity, at least about 75% sequence identity, at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence identity with the sequence of the reference nucleic acid or polypeptide.

[0171] As used herein, “position corresponding to position n,” wherein n is any number, refers to an amino acid position of a subject polypeptide that aligns with position n of a reference polypeptide after aligning the amino acid sequences of the subject and reference polypeptides and introducing gaps. Alignment for purposes of whether a position of a subject polypeptide corresponds with position n of a reference polypeptide can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, CLUSTAL OMEGA, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for alignment, including any parameters needed to achieve maximal alignment over the full length of two sequences being compared. In some embodiments, the subject polypeptide and the reference polypeptide are of different lengths.Attorney Reference No. 2920951-538977

[0172] A “point mutation” is a mutation that involves a single amino acid residue. The mutation may be the loss of an amino acid, substitution of one amino acid residue for another, or the insertion of an additional amino acid residue.

[0173] An “amino acid substitution” refers to the replacement of one amino acid in a polypeptide with another amino acid. In some embodiments, an amino acid substitution is a conservative substitution. Nonlimiting exemplary conservative amino acid substitutions are shown in Table 3. Amino acid substitutions may be introduced into a molecule of interest and the products screened for a desired activity, for example, retained / improved antigen binding, decreased immunogenicity, or improved ADCC or CDC or enhanced pharmacokinetics.Table 3.Original Residue Exemplary SubstitutionsAla (A) Val; Leu; IleArg (R) Lys; Gin; AsnAsn (N) Gin; His; Asp; Lys; ArgAsp (D) Glu; AsnCys (C) Ser; AlaGln (Q) Asn; GluGlu (E) Asp; GinGly (G) AlaHis (H) Asn; Gin; Lys; ArgIle (I) Leu; Val; Met; Ala; Phe; NorleucineLeu (L) Norleucine; Ile; Val; Met; Ala; PheLys (K) Arg; Gin; AsnMet (M) Leu; Phe; IlePhe (F) Trp; Leu; Val; Ile; Ala; TyrPro (P) AlaSer (S) ThrThr (T) Val; SerTrp (W) Tyr; PheTyr (Y) Trp; Phe; Thr; SerVal (V) Ile; Leu; Met; Phe; Ala; Norleucine

[0174] Amino acids may be grouped according to common side-chain properties:(1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile;(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;(3) acidic: Asp, Glu;(4) basic: His, Lys, Arg;(5) residues that influence chain orientation: Gly, Pro;(6) aromatic: Trp, Tyr, Phe.Attorney Reference No. 2920951-538977

[0175] Conservative substitutions may entail exchanging a member of one of these classes with a member of the same class. Non-conservative substitutions will entail exchanging a member of one of these classes with another class.

[0176] Conservative substitutions may be made in accordance with the below Table 4. Methods for predicting tolerance to protein modification may be found in, for example, Guo et al., Proc. Natl. Acad. Sci., USA, 101(25):9205-9210 (2004), the contents of which are incorporated by reference in their entireties.Table 4: Conservative Amino Acid substitutionConservative Amino Acid SubstitutionsAmino Acid Substitutions (others are known in the art)Ala Ser. Gly, CysArg Lys, Gln, HisAsn Gln, His, Glu, AspAsp Glu, Asn, GinCys Ser, Met, ThrGln Asn, Lys, Glu, Asp, ArgGlu Asp, Asn, GinGly Pro, Ala, SerHis Asn, Glu, LysIle Leu, Val, Met, AlaLeu Ile, Val, Met, AlaLys Arg, Gin, HisMet Leu, Ile, Val, Ala, PhePhe Met, Leu, Tyr, Trp, HisSer Thr, Cys, AlaThr Ser, Val, AlaTrp Tyr, PheTyr Trp, Phe, HisVal Ile, Leu, Met, Ala, Thr

[0177] In another embodiment, conservative substitutions may be those shown in the below under the heading of “conservative substitutions.” If such substitutions result in a change in biological activity, then more substantial changes, denominated “exemplary substitutions” in Table 5, may be introduced and the products screened if needed.Table 5: Amino Acid substitutionAttorney Reference No. 2920951-538977..Original Residue{naturallyoccurring amino Conservativeacid) Stsbs i tio Exemplary Sub^inmons Ala (A) Val; Leu; IleArg (R) Lys Lys; Gln; AsnAsn (N) Gln Gln; His; Asp, Lys; ArgAsp (D) Glu Glu; AsnCys (C) Ser Ser; AlaGln (Q) Asn Asn; GluGlu (E) Asp Asp; GlnGly (G) Ala AlaHis (H) Arg Asn; Gln; Lys; ArgIle (I) Leu Leu; Val; Met; Ala; Phe;NerleucineLeu (L) Ile Norleucine; Ile; Val; Met;Ala; PheLys (K) Arg Arg; Gln; AsnMet (M) Leu Leu; Phe; IlePhe (F) Tyr Leu; Val; Ile; Ala; TyrPro (P) Ala AlaSer (S) Thr ThrThr (T) Ser SerTrp (W) Tyr Tyr; PheTyr (Y) Phe Trp; Phe; Thr; SerVal (V) Leu Ile; Leu; Met; Phe; Ala;Norleucine

[0178] The term “vector” is used to describe a polynucleotide that can be engineered to contain a cloned polynucleotide or polynucleotides that can be propagated in a host cell. A vector can include one or more of the following elements: an origin of replication, one or more regulatory sequences (such as, for example, promoters or enhancers) that regulate the expression of the polypeptide of interest, or one or more selectable marker genes (such as, for example, antibiotic resistance genes and genes that can be used in colorimetric assays, for example, P-galactosidase). The term “expression vector” refers to a vector that is used to express a polypeptide of interest in a host cell.

[0179] A “host cell” refers to a cell that may be or has been a recipient of a vector or isolated polynucleotide. Host cells may be prokaryotic cells or eukaryotic cells. Exemplary eukaryotic cells include mammalian cells, such as primate or non-primate animal cells;Attorney Reference No. 2920951-538977fungal cells, such as yeast; plant cells; and insect cells. Nonlimiting exemplary mammalian cells include, but are not limited to, NSO cells, PER. C6® cells (Crucell), 293 cells, and CHO cells, and their derivatives, such as 293-6E, DG44, CHO-S, and CHO-K cells. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected in vivo with a polynucleotide(s) encoding an amino acid sequence(s) provided herein.

[0180] The term “isolated” as used herein refers to a molecule that has been separated from at least some of the components with which it is typically found in nature or produced. For example, a polypeptide is referred to as “isolated” when it is separated from at least some of the components of the cell in which it was produced. Where a polypeptide is secreted by a cell after expression, physically separating the supernatant containing the polypeptide from the cell that produced it is considered to be “isolating” the polypeptide. Similarly, a polynucleotide is referred to as “isolated” when it is not part of the larger polynucleotide (such as, for example, genomic DNA or mitochondrial DNA, in the case of a DNA polynucleotide) in which it is typically found in nature, or is separated from at least some of the components of the cell in which it was produced, for example, in the case of an RNA polynucleotide. Thus, a DNA polynucleotide that is contained in a vector inside a host cell may be referred to as “isolated.” In some embodiments, the parvovirus antibody is purified using chromatography, such as size exclusion chromatography, ion exchange chromatography, protein A column chromatography, hydrophobic interaction chromatography, and CHT chromatography.

[0181] To “reduce” or “inhibit” means to decrease, reduce, or arrest an activity, function, or amount as compared to a reference. In some embodiments, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 20% or greater. In some embodiments, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 50% or greater. In some embodiments, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 75%, 85%, 90%, 95%, or greater. In some embodiments, the amount noted above is inhibited or decreased over a period of time, relative to a control dose (such as a placebo) over the same period of time. A “reference” as used herein, refers to any sample, standard, or level that is used for comparison purposes. A reference may be obtained from a healthy or non-diseased sample. In some examples, a reference is obtained from a non-diseased or nontreated sample of a companion animal. In some examples, a reference is obtained from one or more healthy animals of a particular species, which are not the animal being tested or treated.Attorney Reference No. 2920951-538977

[0182] The term “substantially reduced,” as used herein, denotes a sufficiently high degree of reduction between a numeric value and a reference numeric value such that one of skill in the art would consider the difference between the two values to be of statistical significance within the context of the biological characteristic measured by said values. In some embodiments, the substantially reduced numeric values is reduced by greater than about any one of 10%, 15% 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the reference value.

[0183] As described herein, stability is measured as no change in material attributes during shelflife while the composition meets specifications. Representative specifications may include to potency, content, purity, and / or sterility. Shelf-life stability refers to no impact on efficacy or safety during the shelflife of the product.

[0184] In some embodiments, an parvovirus antibody or compositions described herein may reduce parvovirus titers in a canine or a feline by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to parvovirus titers in the absence of the antibody, as measured by a Hemagglutination Inhibition (HI) assay or Virus Neutralization (VN) assay. In some embodiments, the reduction in parvovirus titer is between 10% and 15%, between 10% and 20%, between 10% and 25%, between 10% and 30%, between 10% and 35%, between 10% and 40%, between 10% and 45%, between 10% and 50%, between 10% and 60%, between 10% and 70%, between 10% and 80%, between 10% and 90%, between 10% and 100%, between 15% and 20%, between 15% and 25%, between 15% and 30%, between 15% and 35%, between 15% and 40%, between 15% and 45%, between 15% and 50%, between 15% and 60%, between 15% and 70%, between 15% and 80%, between 15% and 90%, between 15% and 100%, between 20% and 25%, between 20% and 30%, between 20% and 35%, between 20% and 40%, between 20% and 45%, between 20% and 50%, between 20% and 60%, between 20% and 70%, between 20% and 80%, between 20% and 90%, between 20% and 100%, between 25% and 30%, between 25% and 35%, between 25% and 40%, between 25% and 45%, between 25% and 50%, between 25% and 60%, between 25% and 70%, between 25% and 80%, between 25% and 90%, between 25% and 100%, between 30% and 35%, between 30% and 40%, between 30% and 45%, between 30% and 50%, between 30% and 60%, between 30% and 70%, between 30% and 80%, between 30% and 90%, between 30% and 100%, between 35% and 40%, between 35% and 45%, between 35% and 50%, between 35% and 60%, between 35% and 70%, between 35% and 80%, between 35% and 90%, between 35% and 100%, between 40% and 45%,Attorney Reference No. 2920951-538977between 40% and 50%, between 40% and 60%, between 40% and 70%, between 40% and 80%, between 40% and 90%, between 40% and 100%, between 45% and 50%, between 45% and 60%, between 45% and 70%, between 45% and 80%, between 45% and 90%, between 45% and 100%, between 50% and 60%, between 50% and 70%, between 50% and 80%, between 50% and 90%, between 50% and 100%, between 60% and 70%, between 60% and 80%, between 60% and 90%, between 60% and 100%, between 70% and 80%, between 70% and 90%, between 70% and 100%, between 80% and 90%, between 80% and 100%, or between 90% and 100%.

[0185] A detailed discussion of the parvovirus antibodies as well as additional antibodies capable of use with the instant disclosure may be found in U. S. Applications Nos 63 / 030,123, 62 / 968,970, 62 / 880,650, and 17 / 630,685, the content of each is incorporated by reference herein in its entirety.Exemplary Pharmaceutical Compositions

[0186] A “pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid, or liquid filler, diluent, encapsulating material, formulation auxiliary, or carrier conventional in the art for use with a therapeutic agent that together comprise a “pharmaceutical composition” for administration to a subject. A pharmaceutically acceptable carrier is nontoxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. The pharmaceutically acceptable carrier is appropriate for the formulation employed. Examples of pharmaceutically acceptable carriers include alumina; aluminum stearate; lecithin; serum proteins, such as human serum albumin, canine or other animal albumin; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, or magnesium trisilicate; polyvinyl pyrrolidone, cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids including, but not limited to, arginine.

[0187] The pharmaceutical composition can be stored in lyophilized form. Thus, in some embodiments, the preparation process includes a lyophilization step. The lyophilized composition may then be reformulated, typically as an aqueous composition suitable for parenteral administration, prior to administration to the dog, cat, or horse. In other embodiments, particularly where the antibody is highly stable to thermal and oxidative denaturation, the pharmaceutical composition can be stored as a liquid, i.e., as an aqueous composition, which may be administered directly, or with appropriate dilution, to the dog,Attorney Reference No. 2920951-538977cat, or horse. A lyophilized composition can be reconstituted with sterile Water for Injection (WFI). Anti-bacterial agents (e.g., bacteriostatic reagents, such benzyl alcohol) may be included. Thus, the invention provides pharmaceutical compositions in solid or liquid form.

[0188] In some embodiments, the disclosure provides for treatment with a composition comprising an effective amount of a canine parvovirus antibody for providing passive immunity against infection with a canine or feline parvovirus and / or treating parvoviral infection in companion animals, such as dogs and cats,

[0189] In an aspect, compositions described herein are administered in a single dose formulation. In other aspects, compositions described herein comprise about 2 mg / ml, about 3 mg / ml, about 5 mg / ml, about 6.25 mg / ml, about 7 mg / ml, about 7.5 mg / ml, about 8 mg / ml, about 8.5 mg / ml, about 9 mg / ml, about 9.5 mg / ml, about 10 mg / ml, about 10.5 mg / ml, about 11 mg / ml, about 11.5 mg / ml, about 12 mg / ml, about 12.5 mg / ml, about 13 mg / ml, about 13.5 mg / ml, about 14 mg / ml, about 14.5 mg / ml, about 15 mg / ml, about 15.5 mg / ml, about 16 mg / ml, about 16.5 mg / ml, about 17 mg / ml, about 17.5 mg / ml, about 18 mg / ml, about 18.5 mg / ml, about 19 mg / ml, about 19.5 mg / ml, about 20 mg / ml, about 20.5 mg / ml, about 21 mg / ml, about 21.5 mg / ml, about 22.5 mg / ml, about 25 mg / ml, about 30 mg / ml, about 35 mg / ml, about 40 mg / ml, about 45 mg / ml, about 50 mg / ml, about 55 mg / ml, about 60 mg / ml, about 65 mg / ml, or about 70 mg / ml of a parvovirus antibody.

[0190] In some embodiments, the concentration % (w / v) of the parvovirus antibody in a composition is selected from the group consisting of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0% and any other suitable concentration. In some embodiments, the concentration % (w / v) of the parvovirus antibody is in a range of about 0. 1% to about 10%. In some embodiments, the concentration % (w / v) of the parvovirus antibody is in a range of about 0.5% to about 5%. In some embodiments, the concentration % (w / v) of the parvovirus antibody is in a range of about 0.2% to about 2%.

[0191] In some embodiments, the dose volume of a liquid composition of the parvovirus antibody is selected from the group consisting of about 0.05 ml, about 0.1 ml, about 0.2 ml, about 0.3 ml, about 0.4 ml, about 0.5 ml, about 0.6 ml, about 0.7 ml, about 0.8 ml, about 0.9 ml, about 1 ml, about 2 ml, about 3 ml, about 4 ml, about 5 ml, about 10 ml, about 20 ml, about 25 ml, about 30 ml, about 40 ml, about 50 ml, about 60 ml, about 70 ml, about 80 ml, about 90 ml, about 100 ml, about 110 ml, about 120 ml, about 130 ml, about 140 ml, about 150 ml, about 160 ml, about 180 ml, and any suitable volume. In some embodiments, theAttorney Reference No. 2920951-538977dose volume of a liquid composition of the parvovirus antibody is in a range of about 0.05 ml to about 250 ml.

[0192] In some embodiments, the compositions described herein comprise a liquid solution including a parvovirus antibody, a buffering agent, an isotonic agent, and a surfactant. In some embodiments, the buffering agent is histidine. In some embodiments, the compositions comprise an antioxidant. In some embodiments, the antioxidant is methionine. In some embodiments, the isotonic agent is sucrose. In some embodiments, the compositions comprise one or more surfactants. In an embodiment, the surfactant is a poloxamer, for example poloxamer 188. In an embodiment, the surfactant is a polysorbate. In further embodiments, surfactants for use with the described compositions include poloxamer, poloxamer-188, polysorbate, and / or polysorbate-20. In preferred aspects, the surfactant comprises poloxamer-188 or polysorbate-20.

[0193] In other embodiments, the disclosure provides for compositions comprising at least one surfactant. A surfactant (also known as a surfaceactive agent) is a component which lowers surface tension at the interface between two liquids or between a liquid and solid. Some surfactants include, but are not limited to, glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters, sorbitan esters including sorbitan monooleate (Span® 20), polyvinyl alcohol, polysorbates including polysorbate 20 and polysorbate 80, d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS). Vitamin E TPGS (D-a-Tocopheryl polyethylene glycol 1000 succinate), sodium lauryl sulfate (SLS), co-polymers of ethylene oxide and propylene oxide (e.g. poloxamers such as Poloxamer 124, 188, 338, and 407, and LUTROL® F87 and the like), polyethylene glycol castor oil derivatives including polyoxyl 35 castor oil (Cremophor® EL), polyoxyl 40 hydrogenated castor oil (Cremophor® RH 40), polyoxyl 60 hydrogenated castor oil (Cremophor® RH60); propylene glycol monolaurate(L AUROGLYCOL®); glyceride esters including glycerol capryl ate / caprate (CAPMUL® MCM), polyglycolized glycerides (GELUCIRE®, such as Gelucire® 44 / 14). PEG 300 caprylic / capric glycerides (Softigen® 767), PEG 400 caprylic / capric glycerides (Labrasol®), PEG 300 oleic glycerides (Labrafil® M-1944CS). PEG 300 linoleic glycerides (Labrafil® M-2125CS); polyethylene glycol stearates and polyethylene glycol hydroxy stearates including polyoxyl 8 stearate (PEG 400 monostearate), polyoxyl 40 stearate (PEG 1750 monostearate), PEG3350, and the like. Polyethylene glycol stearates (synonyms include macrogol stearates, polyoxyl stearates, polyoxyethylene stearates, ethoxylated stearates; CAS No. 9004-99-3, 9005-08-7) are mixtures of mono- and distearate esters of mixed polyoxyethylene polymers.Attorney Reference No. 2920951-538977Polyethylene glycol hydroxy stearate is a mixture of mono- and diesters of hydroxystearic acid with polyethylene glycols. One polyethylene glycol hydroxystearate that may be used in the compositions is polyethylene glycol 12-hydroxy stearate. The compositions may include the surfactant polyethylene glycol 15 12-hydroxystearate (Solutol® HS 15 from BASF), a mixture of mono- and diesters of 12-hydroxy stearic acid with 15 moles of ethylene oxide. The compositions may include polyoxyl 35 castor oil (Cremophor® EL) as a surfactant. The compositions may include polyoxyl 40 hydrogenated castor oil (Cremophor® RH 40) or polyoxyl 60 hydrogenated castor oil (Cremophor® RH60) as surfactants.

[0194] In some embodiments, the total amount of the one or more surfactants in the composition is about 0.01% (w / v), 0.02% (w / v), 0.03% (w / v), 0.04% (w / v), 0.05% (w / v), 0.06% (w / v), 0.07% (w / v), 0.08% (w / v / ), 0.09% (w / v), 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v) or more. In some embodiments, the total amount of the surfactants) in the composition ranges from 0.01-0.10% (w / v). In some embodiments, the concentration % (w / v) of the parvovirus antibody is in a range of about 0.05% to about 0.5%. In some embodiments, the concentration % (w / v) of the parvovirus antibody is in a range of about 0.02% to about 0.2%.

[0195] In some embodiments, the pharmaceutical compositions described herein include one or more chelating agents. In some embodiments, the chelating agent is ethylenediaminetetraacetic acid (EDTA). Non-limiting representative chelating agents suitable according to the invention include citric acid; phosphates; disodium EDTA; tetrasodium EDTA; ethylene glycol-bis-(b-aminoethylether)-N, N, N’, N’-tetraacetic acid (EGTA); l,2-bis(2-aminophenoxy)ethane-N, N, N’, N’-tetraacetic acid(BAPTA); ethylene-N, N’-diglycine (EDDA); 2,2’-(ethylendiimino)-dibutyric acid (EBDA); lauroyl EDTA; dilauroyl EDTA, triethylene tetramine dihydrochloride (TRIEN), diethylenetriamin-pentaacetic acid (DPTA), triethylenetetramine hexaacetic acid (TTG), deferoxamine, Dimercaprol, zinc citrate, penicilamine succimer, Editronate, and edetate calcium disodium.

[0196] In some embodiments, the pharmaceutical composition described herein also contains at least one buffering agent, which may increase the stability of the composition. Examples of suitable buffering agents include, but are not limited to, citric acid monohydrate, histidine, monothioglycerol, niacinamide, phosphoric acid, potassium metabisulfite, sodium ascorbate, sodium bisulfate acetone, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium thiosulfate, tartaric acid, or any derivative or combination thereof. Other examples of suitable buffering agents include, but are not limited to, cysteine hydrochloride monohydrate,Attorney Reference No. 2920951-538977thiolyglycolic acid, thiolacetic acid, dithiothreitol, reduced glutathione, thiourea, alphathioglycerol, cysteine, acetylcysteine, mercaptoethane, sulfonic acid, metabisulfite, ascorbic acid, ascorbic acid derivatives (e.g., ascorbyl palmitate), sodium citrate, an organic compound having at least one thiol, an alkyl polyhydroxylated compound, a cycloalkyl polyhydroxylated compound, a hydroxypolycarboxylic acid, an alpha-hydroxy polycarboxylic acid (e.g., citric acid), tocotrienol, dimethyl glycine, betaine, butylated hydroxyanisole, butylated hydroxytoluene, tocopherol, polyethylene glycol, succinate, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, hydroquinone, hydroxycoumarins, ethanolamine, lecithin, cephalin, malic acid, sorbitol, phosphoric acid, thiodipropionic acid and its esters, dithiocarbamates or any combination thereof. In some embodiments, the pharmaceutical composition described herein also contains at least one antioxidant. In some embodiments, the antioxidant is methionine.

[0197] In some embodiments, the amount % (w / v) of the chelating agent or antioxidant in the compositions described herein is about 0.001% (w / v) to about 5.0% (w / v). In some embodiments, the amount % (w / v) of the chelating agent or antioxidant is about 0.001% (w / v), about 0.005% (w / v), about 0.010% (w / v), about 0.015% (w / v), about 0.017% (w / v), about 0.020% (w / v), about 0.030% (w / v), about 0.040% (w / v), about 0.045% (w / v), about 0.050% (w / v), about 0.052% (w / v), about 0.055% (w / v), about 0.060% (w / v), about 0.070% (w / v), about 0.080% (w / v), about 0.10% (w / v), about 1.0% (w / v), about 1.3% (w / v), about 1.5% (w / v), about 1.7% (w / v), about 2.0% (w / v), about 2.2% (w / v), about 2.3% (w / v), about 2.5% (w / v), about 2.7% (w / v), about 2.8% (w / v), about 3.0% (w / v), about 3.2% (w / v), about 3.5% (w / v), about 3.6% (w / v), about 4.0% (w / v), about 4.7% (w / v), or any other suitable amount of antioxidant % (w / v) from about 0.001% (w / v) to about 5.0% (w / v). In some embodiments, the amount % (w / v) of the chelating agent or antioxidant is about 0.01% (w / v) to about 0.1% (w / v).

[0198] In some embodiments, the amount % (w / v) of the chelating agent in the compositions described herein is about 0.001% (w / v) to about 0.05% (w / v), or about 0.01% (w / v) to about 0.05% (w / v), or about 0.01% (w / v) to about 0.02% (w / v). In aspects, the chelating agent comprises EDTA.

[0199] In some embodiments, the amount % (w / v) of the antioxidant in the compositions described herein is about 0.01% (w / v) to about 0.2% (w / v), or about 0.01% (w / v) to about 0.1% (w / v), or about 0.06% (w / v) to about 0.08% (w / v). In aspects, the antioxidant comprises methionine.Attorney Reference No. 2920951-538977

[0200] In other embodiments, the amount % (w / v) of the buffer species in the compositions described herein is about 0.1% (w / v) to about 1.0% (w / v), or about 0.1% (w / v) to about 0.5% (w / v), or about 0.2% (w / v) to about 0.4% (w / v). In aspects, the buffer species comprises histidine.

[0201] In other embodiments, the compositions described herein comprise:(a) a buffer species in an amount of about 0.1% (w / v) to about 1.0% (w / v), or about 0.1% (w / v) to about 0.5% (w / v), or about 0.2% (w / v) to about 0.4% (w / v) and in aspects, the buffer species comprises histidine;(b) a chelating agent in amount of about 0.001% (w / v) to about 0.05% (w / v), or about 0.01% (w / v) to about 0.05% (w / v), or about 0.01% (w / v) to about 0.02% (w / v) and in aspects, the chelating agent comprises EDTA;(c) an antioxidant in an amount of about 0.01% (w / v) to about 0.2% (w / v), or about 0.01% (w / v) to about 0.1% (w / v), or about 0.06% (w / v) to about 0.08% (w / v) and in aspects, the antioxidant comprises methionine.

[0202] In some embodiments, the concentration of the buffering agent in the compositions described herein ranges from about 0.01 mM to about 50 mM. In some embodiments, the concentration of the buffering agent is about 0.02 mM, about 0.03 mM, about 0.05 mM, about 0.08 mM, about 0.09 mM, about 0.10 mM, about 0.12 mM, about 0.13 mM, about 0.15 mM, about 0.18 mM, about 0.20 mM, about 0.22 mM, about 0.25 mM, about 0.27 mM, about 0.30 mM, about 0.40 mM, about 0.45 mM, about 0.50 mM, about 0.60 mM, about 0.80 mM, about 1.2 mM, about 1.5 mM, about 2.0 mM, about 2.5 mM, about 3.0 mM, about 3.5 mM, about 4.0 mM, about 5.0 mM, about 6.0 mM, about 7.5 mM, about 8.0 mM, about 9 mM, about 9.5 mM, about 10 mM, about 20 mM, about 30 mM, about 40 mM or any other suitable concentration of buffering agent from about 0.01 mM to about 50 mM. In some embodiments, the concentration of the buffering agent is about 5 mM to about 30 mM. In some embodiments, the concentration of the buffering agent is about 20 mM.

[0203] In some embodiments, the composition contains at least one buffering agent, which may maintain the pH of the formulation within an acceptable range as described herein. In some embodiments, the buffer is used to maintain the pH of the composition between about 2 and about 9. In some embodiments, the pH of the composition is from about pH 2 to about pH 8, pH 3 to about pH 8, or pH 4 to about pH 8. In some embodiments, the pH is about pH 4.5, about pH 4.6, about pH 4.8, about pH 5.0, about pH 5.5, about pH 6.2, about pH 6.5, about pH 7.5, or any other suitable pH value from about pH4 to about pH 8. In some embodiments, the pH of the aqueous formulation is about pH 7. In some embodiments,Attorney Reference No. 2920951-538977the pH of the aqueous formulation is about pH 8. The pH of the pharmaceutical compositions may be in the range of from about pH 5 to about pH 8, when administered. The compositions of the invention are sterile if they are to be used for therapeutic purposes. Sterility can be achieved by any of several means known in the art, including by filtration through sterile filtration membranes (e.g., 0.2 micron membranes). Sterility may be maintained with or without anti-bacterial agents.

[0204] In some embodiments, the buffering agent is a pharmaceutically acceptable salt or acid of citrate, phosphate, acetate, glutamate, tartrate, benzoate, lactate, histidine or other amino acids, gluconate, malate, tryptophan, succinate, formate, propionate, carbonate, mesilate from methansulfonic acid, gluconolactone, lysine, or any combination thereof adjusted to an appropriate pH, as described herein, with acid (for example, hydrochloric acid) or base (for example, sodium hydroxide). In an embodiment, the buffering agent is tris(hydroxymethyl)aminomethane (Tris). In an embodiment, the composition does not comprise sodium chloride (NaCl).

[0205] In some embodiments, the amount % (w / v) of the buffering agent in compositions described herein is about 0.05% (w / v) to about 2% (w / v). In some embodiment, the amount % (w / v) of the buffering agent lyophilized form is about 0.08% (w / v), about 0.10% (w / v), about 0.15% (w / v), about 1.0% (w / v), about 1.3% (w / v), about 1.5% (w / v), about 1.7% (w / v), about 0.20% (w / v), about 0.22% (w / v), about 0.25% (w / v), about 0.26% (w / v), about 0.27% (w / v), about 0.28% (w / v), about 0.30% (w / v), about 0.35% (w / v), about 0.40% (w / v), about 0.50% (w / v), about 0.60% (w / v), about 0.70% (w / v), about 0.80% (w / v), about 1.2% (w / v), about 1.4% (w / v), about 1.5% (w / v), about 1.7% (w / v), or any other suitable amount of buffering agent % (w / v) from about 0.05% (w / v) to about 2.0% (w / v). In some embodiments, the amount % (w / v) of the buffering agent is about 0.1% (w / v) to about 1% (w / v).

[0206] In some embodiments, the concentration of the buffering agent in a composition described herein prior to administration ranges from about 0.01 mg / ml to about 10 mg / ml. In some embodiments the concentration is about 0.02 mg / ml, about 0.03 mg / ml, about 0.05 mg / ml, about 0.08 mg / ml, about 0.09 mg / ml, about 0.10 mg / ml, about 0.12 mg / ml, about 0.13 mg / ml, about 0.15 mg / ml, about 0.30 mg / ml, about 0.5 mg / ml, about 0.8 mg / ml, about 1.2 mg / ml, about 1.5 mg / ml, about 2.0 mg / ml, about 2.5 mg / ml, about 3.0 mg / ml, about 3.5 mg / ml, about 4.0 mg / ml, about 5.0 mg / ml, about 6.0 mg / ml, about 7.5 mg / ml, about 8.0 mg / ml, about 9 mg / ml, about 9.5 mg / ml, or any other suitable concentration of buffering agent from about 0.01 mg / ml to about 20mg / ml.Attorney Reference No. 2920951-538977

[0207] In some embodiments, a composition described herein also contains one or more isotonic agents, which may maintain the osmolality of the formulation in a range that is physiologically compatible. Suitable agents for adjusting the tonicity of a composition described herein include, but are not limited to, mannitol, sorbitol, maltitol, glycerol, sucrose, glucose, dextrose, levulose, fructose, lactose, polyethylene glycols 400 to 4000, phosphates, sodium chloride, potassium chloride, calcium chloride, calcium glucono-glucoheptonate, dimethyl sulfone. In some embodiments, the isotonic agent is sucrose.

[0208] In some embodiments, the amount % (w / v) of the isotonic agent in the composition described herein prior to reconstitution is about 1% (w / v) to about 20% (w / v). In some embodiments, the amount % (w / v) of the isotonic agent is about 1% (w / v), about 2% (w / v), about 3% (w / v), about 4% (w / v), about 5% (w / v), about 6% (w / v), about 7% (w / v), about 8% (w / v), about 9% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), about 15% (w / v), about 16% (w / v), about 17% (w / v), about 18% (w / v), about 19% (w / v), or any other suitable amount of isotonic agent % (w / v) from about 1% (w / v) to about 20% (w / v). In some embodiments, the amount % (w / v) of isotonic agent is about 5% (w / v) to about 15% (w / v). In some embodiments, the amount % (w / v) of isotonic agent is about 7% (w / v) to about 9% (w / v). In some embodiments, the amount of isotonic agent % (w / v) is about 8%.Representative Uses of Antibodies and Pharmaceutical Compositions

[0209] The antibodies or pharmaceutical compositions comprising the antibodies of the invention may be usefill for providing passive immunity against infection with parvovirus and / or treating a parvoviral infection. As used herein, a “parvoviral infection” means a condition associated with, caused by, or characterized by, a parvoviral infection. Such conditions include, but are not limited to, infections confirmed by cage-side ELISA tests, hemagglutination assay (HA), histopathology, virus isolation or virus titers, or PCR.Infections with parvovirus often include fever, vomiting, diarrhea, lymphopenia / leukopenia, dehydration, secondary septicemia, dehydration, loss of appetite, abdominal pain, lethargy, depression, and / or nasal discharge.

[0210] As used herein, “treatment” is an approach for obtaining beneficial or desired clinical results. “Treatment” as used herein, covers any administration or application of a therapeutic for disease in a subject, such as a mammal, including a human and a companion animal (e.g., a canine or feline). For purposes of this disclosure, beneficial or desired clinical results include, but are not limited to, any one or more of: alleviation of one or moreAttorney Reference No. 2920951-538977symptoms, prevention of mortality, diminishment of extent and severity of disease, preventing or delaying spread of disease, eliminating or shorting duration of viral shedding, preventing or delaying recurrence of disease, preventing or decreasing viral cytopathic effects, delay or slowing of disease progression, amelioration of the disease state, inhibiting the disease or progression of the disease, resolution of clinical signs of disease, inhibiting or slowing the disease or its progression, arresting its development, and remission (whether partial or total). Also encompassed by “treatment” is a reduction of pathological consequence of a proliferative disease. The methods provided herein contemplate any one or more of these aspects of treatment. In-line with the above, the term treatment does not require one-hundred percent removal of all aspects of the disorder.

[0211] In some embodiments, a parvovirus antibody or pharmaceutical compositions comprising it can be utilized in accordance with the methods herein to provide passive immunity against infection parvovirus and / or treat parvoviral infections. In some embodiments, a parvovirus antibody or pharmaceutical compositions is administered to subject, such as a companion animal (e.g., a canine or a feline) or a human to provide passive immunity against infection with parvovirus and / or treat an a parvoviral infection.

[0212] A “therapeutically effective amount” of a substance / molecule, agonist or antagonist may vary according to factors such as the type of disease to be treated, the disease state, the immune status of the individual subject, the virulent viral load encountered, the severity and extent of viremia, the severity and course of the disease, the type of therapeutic purpose, any previous therapy, the clinical history, the response to prior treatment, the maternally-derived antibody passive transfer status, the previous immunization status of the individual animal, the discretion of the attending veterinarian, age, sex, and weight of the subject, and the ability of the substance / molecule, agonist or antagonist to elicit a desired response in the subject. A therapeutically effective amount is also one in which any toxic or detrimental effects of the substance / molecule, agonist or antagonist are outweighed by the therapeutically beneficial effects. A therapeutically effective amount may be delivered in one or more administrations. A therapeutically effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result.

[0213] In some embodiments, a parvovirus antibody or pharmaceutical composition comprising a parvovirus antibody is administered parenterally, by subcutaneous administration, intravenous infusion, or intramuscular injection. In some embodiments, a parvovirus antibody or pharmaceutical composition comprising a parvovirus antibody isAttorney Reference No. 2920951-538977administered as a single dose or multiple dose bolus injection. In some embodiments, a parvovirus antibody or pharmaceutical composition comprising a parvovirus antibody is administered by an intramuscular, an intravenous, an intraperitoneal, an intracerebrospinal, a subcutaneous, an intra-arterial, an intrasynovial, an intrathecal, or an inhalation route.

[0214] Parvovirus antibodies described herein may be administered in an amount in the range of 0.01 mg / kg body weight to 100 mg / kg body weight per dose. In some embodiments, parvovirus antibodies may be administered in an amount in the range of 0.5 mg / kg body weight to 50 mg / kg body weight per dose. In some embodiments, parvovirus antibodies may be administered in an amount in the range of 0.1 mg / kg body weight to 10 mg / kg body weight per dose. In some embodiments, parvovirus antibodies may be administered in an amount in the range of 0.1 mg / kg body weight to 100 mg / kg body weight per dose. In some embodiments, parvovirus antibodies may be administered in an amount in the range of 1 mg / kg body weight to 10 mg / kg body weight per dose. In some embodiments, parvovirus antibodies may be administered in an amount in the range of 0.5 mg / kg body weight to 100 mg / kg body, in the range of 1 mg / kg body weight to 100 mg / kg body weight, in the range of 5 mg / kg body weight to 100 mg / kg body weight, in the range of 10 mg / kg body weight to 100 mg / kg body weight, in the range of 20 mg / kg body weight to 100 mg / kg body weight, in the range of 50 mg / kg body weight to 100 mg / kg body weight, in the range of 1 mg / kg body weight to 10 mg / kg body weight, in the range of 5 mg / kg body weight to 10 mg / kg body weight, in the range of 0.5 mg / kg body weight to 10 mg / kg body weight, in the range of 0.01 mg / kg body weight to 0.5 mg / kg body weight, in the range of 0.01 mg / kg body weight to 0.1 mg / kg body weight, or in the range of 5 mg / kg body weight to 50 mg / kg body weight. In some embodiments, parvovirus antibodies may be administered in an amount of 0.5 mg / kg body weight.

[0215] A parvovirus antibody or a pharmaceutical composition comprising a parvovirus antibody can be administered to a subject, such as a human or companion animal (e.g., a canine or a feline) as a single dose, at one time or over a series of treatments. For example, a parvovirus antibody or a pharmaceutical composition comprising a parvovirus antibody may be administered at least once, more than once, at least twice, at least three times, at least four times, or at least five times.

[0216] In some embodiments, the dose is administered once per week for at least two or three consecutive weeks, and in some embodiments, this cycle of treatment is repeated two or more times, optionally interspersed with one or more weeks of no treatment. In other embodiments, the therapeutically effective dose is administered once per day for two to fiveAttorney Reference No. 2920951-538977consecutive days, and in some embodiments, this cycle of treatment is repeated two or more times, optionally interspersed with one or more days or weeks of no treatment.

[0217] In some embodiments, the dose is administered to a subject, such as a human or companion animal (e.g., a canine or a feline) less than 1 week of age, less than 2 weeks of age, less than 3 weeks of age, less than 4 weeks of age, less than 5 weeks of age, less than 6 weeks of age, less than 6 weeks of age, less than 7 weeks of age, less than 8 weeks of age, less than 9 weeks of age, less than 10 weeks of age, less than 11 weeks of age, less than 12 weeks of age, less than 6 months of age, between 0 and 12 weeks of age, between 0 and 10 weeks of age, between 0 and 8 weeks of age, between 0 and 6 weeks of age, between 0 and 4 weeks of age, between 0 and 2 weeks of age, between 4 and 12 weeks of age, between 6 and 12 weeks of age, between 10 and 12 weeks of age, between 4 weeks and 6 months of age, between 2 months and 6 months of age, between 4 months and 6 months of age, between 6 months and 1 year of age, greater than 13 weeks of age, or greater than 1 year of age.

[0218] It may be advantageous to deliver the parvovirus antibody or a nucleic acid encoding the parvovirus antibody to an infant subject prenatally and / or postnatally to provide passive immunity against parvovirus infection. In some embodiments, the parvovirus antibody is administered to a pregnant or nursing maternal subject, such as a human or companion animal (e.g., a canine or a feline). In some embodiments, the parvovirus antibody is administered to the placenta of a pregnant subject.

[0219] In some embodiments, a method of providing passive immunity in an infant subject against infection with a canine or feline parvovirus comprises administering to a pregnant or nursing maternal subject a therapeutically effective amount of a monoclonal antibody that binds to the canine or feline parvovirus. In some embodiments the parvovirus antibody is administered to the placenta of a pregnant subject. In some embodiments, the parvovirus antibody is administered to a nursing subject.

[0220] Provided herein are methods of using the parvovirus antibodies, polypeptides and polynucleotides for detection, diagnosis and monitoring of a parvoviral infection. Provided herein are methods of determining whether a subject will respond to parvovirus antibody therapy. In some embodiments, the method comprises virus serum neutralization. In some embodiments, the method comprises detecting whether the subject has cells that express parvovirus using a parvovirus antibody. In some embodiments, the method of detection comprises contacting the sample with an antibody, polypeptide, or polynucleotide and determining whether the level of binding differs from that of a reference or comparison sample (such as a control). In some embodiments, the method may be useful to determineAttorney Reference No. 2920951-538977whether the antibodies or polypeptides described herein are an appropriate treatment for the subject.

[0221] In some embodiments, the sample is a biological sample. The term “biological sample” means a quantity of a substance from a living thing or formerly living thing. In some embodiments, the biological sample is a swab containing cellular debris, cell or cell / tissue lysate. In some embodiments, the biological sample includes, but is not limited to, blood, (for example, whole blood), plasma, serum, urine, fecal material, synovial fluid, lymphatic tissue and epithelial cells.

[0222] In some embodiments, the cells or cell / tissue lysate are contacted with a parvovirus antibody and the binding between the antibody and the cell is determined. When the test cells show binding activity as compared to a reference cell of the same tissue type, it may indicate that the subject would benefit from treatment with a parvovirus antibody. In some embodiments, the test cells are from tissue of a subject, such as a human or companion animal (e.g., a canine or a feline).

[0223] Various methods known in the art for detecting specific antibody-antigen binding can be used. Exemplary immunoassays which can be conducted include fluorescence polarization immunoassay (FPIA), fluorescence immunoassay (FIA), enzyme immunoassay (EIA), nephelometric inhibition immunoassay (NIA), enzyme linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). An indicator moiety, or label group, can be attached to the subject antibodies and is selected so as to meet the needs of various uses of the method which are often dictated by the availability of assay equipment and compatible immunoassay procedures. Appropriate labels include, without limitation, radionuclides (for example125I,131I,35S,3H, or32P), enzymes (for example, alkaline phosphatase, horseradish peroxidase, luciferase, or b-galactosidase), fluorescent moieties or proteins (for example, fluorescein, rhodamine, phycoerythrin, GFP, or BFP), or luminescent moieties (for example, Qdot™ nanoparticles supplied by the Quantum Dot Corporation, Palo Alto, Calif). General techniques to be used in performing the various immunoassays noted above are known to those of ordinary skill in the art.

[0224] For purposes of diagnosis, the polypeptide including antibodies can be labeled with a detectable moiety including but not limited to radioisotopes, fluorescent labels, and various enzyme-substrate labels known in the art. Methods of conjugating labels to an antibody are known in the art. In some embodiments, the parvovirus antibodies need not be labeled, and the presence thereof can be detected using a second labeled antibody which binds to the first parvovirus antibody. In some embodiments, the parvovirus antibody can beAttorney Reference No. 2920951-538977employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. Zola, Monoclonal Antibodies: A Manual of Techniques, pp. 147-158 (CRC Press, Inc. 1987). The parvovirus antibodies and polypeptides can also be used for in vivo diagnostic assays, such as in vivo imaging.Generally, the antibody or the polypeptide is labeled with a radionuclide (such as "'in,99Tc,14C,131I,125I,3H, or any other radionuclide label, including those outlined herein) so that the cells or tissue of interest can be localized using immunoscintiography. The antibody may also be used as staining reagent in pathology using techniques well known in the art.

[0225] In some embodiments, a first antibody is used for a diagnostic and a second antibody is used as a therapeutic. In some embodiments, the first and second antibodies are different. In some embodiments, the first and second antibodies can both bind to the antigen at the same time, by binding to separate epitopes.

[0226] The following examples illustrate particular aspects of the disclosure and are not intended in any way to limit the disclosure.EXAMPLES

[0227] Example 1. Chimeric canine antibodies Mab A and Mab B

[0228] Structural analysis of canine parvovirus and feline parvovirus complexed with antibody fragments from eight different neutralizing monoclonal antibodies were reported in Hafenstein S., et al, J Virol. 2009 Jun, 83(11):5556-66, the content of which is incorporated by reference in its entirety. Incomplete amino acid sequence information was provided for rat Mab E and Mab F Fab fragments, which exhibited canine parvovirus neutralization in an in vitro assay. The incomplete amino acid sequences for the variable heavy chain and variable light chain of Mab E are SEQ ID NOs. 81 and 82, respectively. The incomplete amino acid sequences for the variable heavy chain and variable light chain of Mab F are SEQ ID NOs.83 and 84, respectively.

[0229] Three-dimensional protein structure analysis was performed to construct a redesigned first framework region for both heavy and light chains of Mab E and Mab F. The amino acid sequences of the heavy and light chain of redesigned monoclonal antibodies, designated Mab A and Mab B, are SEQ ID NO: 20 (Mab A heavy chain), SEQ ID NO: 22 (Mab A light chain), SEQ ID NO: 62 (Mab B heavy chain), and SEQ ID NO: 64 (Mab B light chain).

[0230] DNA sequences encoding a chimeric antibody were designed for fusions of MabAttorney Reference No. 2920951-538977A VH (SEQ ID NO: 20) and Mab B VH (SEQ ID NO: 62) to canine constant IgG-B heavy chain and Mab A VL (SEQ ID NO: 22) and Mab B LC (SEQ ID NO: 64) to canine constant κ light chain resulting in SEQ ID NO: 23 (Chimeric A HC IgG-B), SEQ ID NO: 66 (Chimeric B HC IgG-B), SEQ ID NO: 25 (Chimeric A LC K), and SEQ ID NO: 68 (Chimeric B LC K). The heavy chain and light chain nucleotide sequences were synthesized chemically and inserted into an expression vector suitable for transfection into a mammalian host cell. Following transfection of heavy and light chain vector pairs into cells and culture, antibodies were affinity purified from the culture media using CaptivA® Protein A Affinity Resin (Repligen). The purified Chimeric Canine Mab A and Mab B antibodies were confirmed by SDS-PAGE analysis (data not shown).

[0231] Chimeric antibodies may also be designed and prepared based on fusions of Mab A VH (SEQ ID NO: 20) and Mab B VH (SEQ ID NO: 62) to canine constant IgG-A, IgG-C, and IgG-D heavy chains.

[0232] Example 2: Chimeric canine antibodies Mab A and Mab B Activity

[0233] Both purified Chimeric Canine Mab A and Mab B (formulated in PBS, pH 7.2 at 200 μg / mL) were used for assessing anti-canine parvovirus activity using a hemagglutination inhibition (HI) assay. The assay was performed at Companion Animal Vaccine and Immuno Diagnostic Service Laboratory, University of Wisconsin, essentially as described by Carmichael, et al., Am J of Vet Res. 1980 May, 41 (5):784-91. Serial dilutions of samples of Chimeric Canine Mab A and Chimeric Canine Mab B incubated with CPV were prepared. Porcine red blood cells were then added. Canine parvovirus induces porcine red blood cells to agglutinate. Both Chimeric Canine Mab A and Chimeric Canine Mab B prevented agglutination. Both antibodies resulted in a CPV-2b HI of 40960, while irrelevant canine IgG produced HI of <20. Most vaccinated dogs are understood to have antibody HI around 1280.

[0234] Furthermore, the activity of the antibodies to prevent live CPV from infecting and destroying cells was analyzed using Virus Serum Neutralization assay.

[0235] Example 3: Variant VH and VL Sequences for Enhanced Expression of Chimeric Canine Mab A and Mab B

[0236] Chimeric Canine Mab A and Chimeric Canine Mab B consistently expressed poorly in transient CHOS or stable CHOK1 cells. To enhance expression levels, three-dimensional protein structure analysis was performed to identify VH and VL amino acidAttorney Reference No. 2920951-538977residues suitable for modification. Multiple constructs with various mutations in VH and VL were generated. The expression level of antibodies having combinations of canine IgG-B with VH and VL variants were tested.

[0237] Enhanced expression variants were analyzed for their specific activity by canine parvovirus HI assay. In these experiments, each of the antibody variants tested was formulated in PBS, pH 7.2 at 200 μg / mL. Both Chimeric Canine Mab A (SEQ ID NOs: 23 and 25) and Chimeric Canine Mab B (SEQ ID NOs: 66 and 68) demonstrated a CPV-2b HI of 10240. Enhanced expression variants, Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69), maintained the same HI value of 10240, while other variants displayed lower specific activity.

[0238] Example 4: Parvovirus Infection Assay Activity (SVN)

[0239] To determine the ability of Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69) to prevent live parvovirus from infecting and destroying cells, a serum virus neutralization (SVN) assay was performed. In this assay, Madin Darby Canine Kidney (MDCK) cells were grown. Serial dilutions of antibody were mixed with a fixed titer of parvovirus. The mixture was then incubated with the cells. After incubation, the cells were examined by microscopy to identify the viral cytopathic effect (CPE). The readout is the final dilution of the antibody sample where it reached limits in preventing parvovirus from causing the cytopathic effect.

[0240] Both Chimeric Canine Mab A v2 (1) kept at 4°C and (2) subjected to 7 freezethaw cycles at 200 ug / tnL had the same activity: SVN for CPV-2b 32000 and SVN for CPV2c 8000.

[0241] Example 5: Stability of Chimeric Canine Mab A v2 and Mab B v2

[0242] Stability of Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) at 25 mg / mL and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69) at 20.5 mg / mL was tested.Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 have similar specific activity by HI assay at a concentration of about 25 mg / mL and about 20.5 mg / mL, respectively.

[0243] Both Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 produced and purified from CHOK1 stable pool can be readily concentrated to 25 mg / mL in PBS, pH7.2, suggesting that both antibodies have no solubility concerns.

[0244] Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 are monomeric (>99%) at neutral pH and after storage for 10 hours at pH 4.1, as assessed by size-exclusionAttorney Reference No. 2920951-538977high performance liquid chromatography (HPLC). In this analysis, monomer and aggregates of antibodies were separated by SEC-HPLC, using Agilent 1100 system, Shodex KW803 column (8 mm x 300 mm) with a KW-G guard column, and mobile phase buffer of 2X PBS pH7.2 (270 mM NaCl, 5.4 mM KCl, 8.6 mM Na2HPO4, 2.8 mM KPO4) at a constant flow rate of 0.5 mL / minute. The column was calibrated using Bio Rad markers (Catalog No. 151-1901) composed of Thyroglobulin, Y-globulin, Ovalbumin, Myoglobin and Vitamin B12.

[0245] Chimeric Canine Mab A v2 real-time stability in (1) PBS, pH 7.2 at 25 mg / mL and (2) 50 mM NaCitrate pH 7, 150 tnM NaCl at 25 mg / mL at various temperatures were evaluated. The HPLC-SEC results at ten months are summarized in Table 6.Table 6.Buffer Temperature %HMW Chimeric Canine Mab A v2 (%monomer)-80 °C < LOQ 100 (control)PBS pH 7.2 -20 °C < LOQ 1004 °C < LOQ 10025 °C 2.1% 97.950 mM -80 °C < LOQ 100NaCitrate pH 7, (control)150 mM NaCl -20 °C < LOQ 100

[0246] Stability was also tested by subjecting the antibodies to three freeze-thaw cycles with freezing at -70 °C and thawing at room temperature. No loss of activity was observed for either antibody in terms of both CPV-2b HI and CPV-2c HI value.

[0247] Stability was further tested by subjecting the antibodies to seven freeze-thaw cycles with freezing at -20 °C and thawing at room temperature. Both antibodies maintained full activity as measured by HI assay.

[0248] Thermostability of the two antibodies in different formulations and across a range of pH was analyzed using differential scanning fluorescence (DSF). The melting temperature (Tm) of each antibody at the different conditions were measured. Buffer and 12 pg of antibody were mixed together with IX Protein thermal shift dye (Applied Biosystem, Catalog No. 4461146). A melting curve was performed with StepOne Real Time PCR System (Applied Biosystem, Catalog No. 4376357). The temperature was increased from 25 °C to 99 °C with a ramp rate of 1% according to the manufacturer’s instructions. The data was analyzed by Protein Thermal Shift™ Software vl.0 (Applied Biosystem, Catalog No.4466038) to determine the Tm, which was calculated as the highest value derived from takingAttorney Reference No. 2920951-538977the first derivative of the protein melting curve. For each of the formulations tested, including PBS pH 7.2, Chimeric Canine Mab A v2 was more stable than Chimeric Canine Mab B v2.

[0249] Example 6: VLP bindings of Chimeric canine antibodies Mab A v2 and Mab B v2

[0250] Apparent affinity of Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69) with parvovirus VLP was measured. First, biotinylated Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 were bound to streptavidin sensor tips. Then, binding of recombinant canine parvovirus CPV2b capsid (Advanced ImmunoChemical Inc Cat #8-CPV) to the Mab-bound sensor tip was assessed.

[0251] Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 antibodies each exhibited affinity to canine CPV 2b VLP with kinetics potentially sufficient for therapeutic activity. The binding analysis was performed using an Octet Biosensor as follows. Briefly, Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69) was biotinylated through amine chemistry. The free unreacted biotin was removed by extensive dialysis. Biotinylated Chimeric Canine Mab A v2 and Chimeric Canine Mab B v2 was captured on streptavidin sensor tips. The association of either Mab A v2 or Mab B v2 and canine CPV 2b VLP (40 |Jg / mL) was monitored for 300 seconds.Dissociation was monitored for 300 seconds. A biotinylated irrelevant canine IgG-B was used as negative control. The data were fit to a 1:1 binding model using ForteBio™ data analysis software to determine the kon, koff, and the Kd. The buffer for dilutions and all binding steps was 20 mM phosphate, 150 mM NaCl, pH 7.2. The Kd of Chimeric Canine Mab A v2 and VLP2b was 9.78 x 10-11M and of Chimeric Canine Mab B v2 and VLP2b was 9.38 x 10-12M (See FIG. 2).

[0252] Example 7: Caninization of Mab A v2 and Mab B v2

[0253] To reduce potential immunogenicity, particularly where repeated administration of antibodies A or B are needed, VH and VL from Mab A v2 and B v2 were subjected to caninization. A number of caninized VH and VL were designed, expressed, and purified. Good expressors were selected for specific activity using CPV2b HI assay. Caninized A HC v3 IgG-B (SEQ ID NO: 37) plus Caninized A LC K (SEQ ID NO: 39) and Caninized A HC v4 IgG-B (SEQ ID NO: 38) plus Caninized A LC K (SEQ ID NO: 39) maintained full activity compared to Chimeric A HC IgG-B (SEQ ID NO: 23) plus Chimeric A LC K (SEQ ID NO:Attorney Reference No. 2920951-53897725) and compared to Chimeric A HC v2 IgG-B (SEQ ID NO: 24) plus Chimeric A LC K (SEQ ID NO: 25). Caninized B HC v3 IgG-B (SEQ ID NO: 79) plus Caninized B LC v3 K (SEQ ID NO: 80) maintained full activity compared to Chimeric B HC IgG-B (SEQ ID NO: 66) plus Chimeric B LC K (SEQ ID NO: 68) and compared to Chimeric B HC v2 IgG-B (SEQ ID NO: 67) plus Chimeric B LC v2 K (SEQ ID NO: 69).

[0254] Example 8: Feline Chimeric Mab A and Mab B

[0255] Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25) and Chimeric Canine Mab B v2 (SEQ ID NOs: 67 and 69) showed activity in a feline parvovirus HI assay. Chimeric Canine Mab A v2 at 200 μg / mL exhibited a feline parvovirus HI of 262144, while Chimeric Canine Mab B v2 at 200ug / ml exhibited a feline parvovirus HI of 131072.

[0256] Thus, Mab A and Mab B may be used in feline Parvovirus (panleukopenia virus) prevention or treatment. Furthermore, chimeric feline Mab A variable heavy chain and feline IgG-1 was designed to pair with chimeric feline Mab A variable light chain and feline kappa (SEQ ID NOs: 31 and 32). To remove potential heterogeneity, a mutation that removes the glycosylation site can be introduced to make chimeric feline Mab A-IgGl paired with an aglycosylated kappa (e.g., SEQ ID NOs: 31 and 33).

[0257] Further, chimeric feline Mab B variable heavy chain and feline IgG-1 was designed to pair with chimeric feline Mab B variable light chain and feline kappa (SEQ ID NOs: 74 and 75). A mutation that removes the glycosylation site can be introduced to make chimeric feline Mab A-IgGl paired with an aglycosylated kappa (e.g., SEQ ID NOs: 74 and 76).

[0258] Example 9. Representative Formulation Preparation

[0259] The composition presented in Table 7 was prepared as follows: a mixture of histidine and sucrose was prepared; the mixture was stirred until the histidine and sucrose dissolved; poloxamer-188 was added to the mixture; the mixture was stirred until the poloxamer-188 dissolved; and a canine parvovirus antibody, Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25), was added to the composition. For these example, a canine parvovirus antibody comprising SEQ ID NO: 24 and SEQ ID NO: 25 (CDR-H1 comprising SEQ ID NO: 4, CDR-H2 comprising SEQ ID NO: 5, CDR-H3 comprising SEQ ID NO: 6, CDR-L1 comprising SEQ ID NO: 13, CDR-L2 comprising SEQ ID NO: 14, and CDR-L3 comprising SEQ ID NO: 15) was utilized. The amounts used are set forth in Table 7.Attorney Reference No. 2920951-538977

[0260] The composition presented in Table 8 was prepared as follows: a mixture of histidine, methionine and sucrose was prepared; the mixture was stirred until the histidine, methionine and sucrose dissolved; poloxamer-188 was added to the mixture; the mixture was stirred until the poloxamer-188 dissolved; and a canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) was added to composition. The amounts used are set forth in Table 8.

[0261] The composition presented in Table 9 was prepared as: a mixture of histidine, methionine and sucrose was prepared; the mixture was stirred until the histidine, methionine and sucrose dissolved; poloxamer-188 was added to the mixture; the mixture was stirred until the poloxamer-188 dissolved; EDTA was added to the mixture; the mixture was stirred until the EDTA dissolved; and a canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) was added to composition. The amounts used are set forth in Table 9.Table 7.Component AmountChimeric Canine Mab A v2; 30 mg / mLSEQ ID NOs: 24 and 25)Histidine 20 mMSucrose 8% w / vPoloxamer-188 0.02% w / vTable 8.Component AmountChimeric Canine Mab A v2; 30 mg / mL(SEQ ID NOs: 24 and 25)Histidine 20 mMMethionine 5 mMAttorney Reference No. 2920951-538977Sucrose 8% w / vPoloxamer-188 0.02% w / vTable 9.Component AmountChimeric Canine Mab A v2; 30 mg / mL(SEQ ID NOs: 24 and 25)Histidine 20 mMSucrose 8% w / vMethionine 5 mMEDTA 0.5 mMPoloxamer-188 0.02% w / v

[0262] Example 10. Buffer Screen

[0263] Buffer systems and pH were reviewed for formulation development screening studies. Buffer and pH effects on canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) were evaluated in multiple buffer systems at 20 mM buffer concentration. In addition to biophysical characterization, the different formulations were stored at 40°C to determine potential degradation pathways.

[0264] As shown in FIG. 3, histidine minimizes deamidation compared to citrate, and lower pH minimizes deamidation but results in the highest rate of monomer loss. Histidine at pH 7.2 was found to be an effective buffer and pH. The phosphate based buffer samples showed low flexibility across the pH range. Slight increases in pH resulted in increases in physical and chemical degradation. Based on these results, phosphate was found to be a poor buffer system for canine parvovirus antibodies (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) compared to other options. Citrate and histidine performed comparably across pH 6.0 - 7.2. However, histidine showed a better ability to mitigate deamidation at higher pH compared to citrate and performed well at pH 7.2.Attorney Reference No. 2920951-538977

[0265] Example 11. Stability Testing

[0266] Canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 15 mg / mL with 20 mM histidine buffer at pH 7.2 and pH 6.0 were tested for stability at 5 °C, 25 °C, and 40 °C at 0, 1, 2, 4, 8 and 12 weeks. Stability samples were prepared at 200 pL aliquot in HPLC max-recovery vials (see Table 10). Samples were frozen at -80°C at pull time. The formulation with 20 mM Histidine at pH 7.2 shows strong stability in SEC monomer testing without the addition of stabilizing excipients at real-time and accelerated conditions. The results of the study also indicate that formulations with 20 mM Histidine at pH 6.0 mitigate deamidation, but have poor physical stability and low predicted colloidal stability (kD = -11 mL / g). The formulation with excipients 5% sucrose, 2 mM methionine and 0.5 mM EDTA showed the greatest stability at 5 °C, 25 °C, and 40 °C. No difference was observed in formulations with poloxamer-188 and polysorbate as respective surfactants. The results also demonstrated that NaCl may have a destabilizing effect as an excipient.Table 10.Formulation Buffer Buffer pH Excipient Excipient Chimeric Canine Mab A Concentration Concentration v2; SEQ ID NOs: 24 and (mM) 25Concentration (mg / mL) H7.2 Histidine 20 7.2 None N / A 15 ControlH7.2 Histidine 20 7.2 Sucrose 5% w / v 15 SucroseH7.2 NaCl Histidine 20 7.2 NaCl 100 mM 15 H7.2 Arg Histidine 20 7.2 Arginine 100 mM 15 H7.2 Gly Histidine 20 7.2 Glycine 100 mM 15 H7.2 Histidine 20 7.2 Methionine + 2 mM + 0.5 15 MetEDTA EDTA mMH7.2 P188 Histidine 20 7.2 Poloxamer 0.02% w / v 15188H7.2 P520 Histidine 20 7.2 Polysorbate 0.02% w / v 1520H6.0 Histidine 20 6 None None 15Control

[0267] Example 12. Agitation Study

[0268] The impact of surfactant on particulate formation in canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) formulations was investigated in an agitation study. Canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 15 mg / mL in 20 mM histidine at pH 7.2 were prepared in the presenceAttorney Reference No. 2920951-538977of 0.02% w / v poloxamer-188, 0.02% w / v polysorbate-20, or no surfactant, respectively. Orbital shaking was conducted at 200 rpm at 24 hours and 72 hours. Control was at time = 0 with no shaking at 5 °C storage and time = 72 hours with no shaking, ambient storage, and no light protection. Packaging was 1.5 mL fill (~50% headspace), 2R vials, and uncoated stopper. Orbital shaking was conducted with no intentional stopper contact at 200 rpm over 72 hours. Analytical assays (SEC, CE-SDS, cIEF) showed no differences between samples, agitation produces visible particulates and insoluble aggregates. Poloxamer-188 and polysorbate-20 both prevent particulate formation at 0.02% w / v compared to formulations without surfactant.

[0269] Example 13. Freeze / Thaw Study

[0270] The impact of excipients on particulate formation during freeze / thaw cycles in canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) formulations was investigated. The same excipients and concentrations were used as described in Example 4. Freeze / thaw was evaluated at 0, 3, and 7 cycles. Samples were frozen at -80 °C for 20-24 hours. Thaw was conducted at 25 °C (controlled) until samples just thawed. Line vials in tray were surrounded with “dummy” vials containing 20 mM histidine at pH 7.2 buffer to minimize thermal variation by vial position. Particulate formation was evaluated using SEC, CE-SDS, cIEF, MFI, A280, and DLS assays. Results showed that the excipients sucrose and glycine minimize particulate formation. Results also showed that IX PBS formulation and glycine have the highest levels of soluble aggregate formation through multiple freeze / thaw cycles. While all other excipients utilized minimized aggregate formation, sucrose and surfactants polysorbate-20 and poloxamer-188 best protected against freeze / thaw stress.

[0271] Example 14. Excipient Combination Study

[0272] Canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 30 mg / mL with 20 mM histidine buffer at pH 7.2 and pH 6.0 and various excipient combinations were tested for stability at 5 °C, 25 °C, and 40 °C at 0, 0.1, 0.25, 0.33, 1, 2, 3, 6, 9, and 12 months (see Table 11). Formulations containing NaCl (5% Sucrose + 50 mM NaCl) have the highest rates of deamidation and fragmentation (see FIGs. 9 and 10). Results also showed that the absence of EDTA leads to significant particulate formation, and poloxamer-188 reduced subvisible particulate formation compared to polysorbate-20.Formulations with poloxamer-188 showed significantly fewer particulates compared toAttorney Reference No. 2920951-538977formulations with polysorbate-20 through 6 months of shelf life. The formulation with 8%w / v sucrose, 2 mM methionine, 0.5 mM EDTA, and 0.02%w / v poloxamer-188 exhibited the greatest stability at 7 months.Table 11.ExcipientPoloxamerFormulation Sucrose Polysorbate Description PH NaCl Methionine EDTA 188# (%w / v) 20 (%w / v)(%w / v)50 0.5Fl 7.2 5% 2 mM 0.02% Comparison of mM mMsurfactants 50 0.5F2 7.2 5% 2 mM 0.02%mM mMLowest potential 0.5 for oxidative F3 7.2 8% 2 mM 0.02%mM degradation Comparison with 0.5F4 7.2 8% 2 mM 0.02% #F3 mMF5 7.2 8% 2 mM 0.02% Methionine vs.EDTA oxidative 0.5F6 7.2 8% 0.02% degradation mMHighest potential for oxidative degradation, F7 7.2 8% 0.02% support inclusion of Methionine or EDTADeamidation 0.5F8 6.0 8% 2 mM 0.02% backup mM

[0273] Example 15. Surfactant Study

[0274] An agitation study was conducted to evaluate the impact of surfactant type, surfactant level, and EDTA quantity on particulate formation in canine parvovirus antibody (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) formulations at 30 mg / mL with 20Attorney Reference No. 2920951-538977mM histidine buffer at pH 7.2 (see Table 12). Results showed that surfactant type and surfactant level have the highest impact on particle formation. Polysorbate-20 performed better at protecting against agitation stress, while the impact of poloxamer-188 is concentration dependent in agitation stress mitigation but exhibits higher shelf-life stability.Table 12.Agitation Excipient SurfactantEDTA Methionine Formulation Combo Surfactant Type Level (mM) (mM)ID Formulation (%w / v)0 2 1 1-PS20 Polysorbate-20 0.01%2 2 2-PS20 Polysorbate-20 0.01% 0.12 3 3-PS20 Polysorbate-20 0.01% 0.52 4 4-PS20 Polysorbate-20 0.02% 02 5 5-PS20 F4 Polysorbate-20 0.02% 0.52 6 6-PS20 Polysorbate-20 0.04% 02 7 7-PS20 Polysorbate-20 0.04% 0.12 8 8-PS20 Polysorbate-20 0.04% 0.52 9 9-P188 Poloxamer-188 0.01% 02 10 10-P188 Poloxamer- 188 0.01% 0.52 11 11-P188 Poloxamer-188 0.02% 0.112 0.02% 212-P188 F3 Poloxamer-188 0.52 13 13-P188 Poloxamer-188 0.04% 02 14 14-P188 Poloxamer-188 0.04% 0.5

[0275] Example 16. Oxidation Study with Hydrogen Peroxide[00276 A hydrogen peroxide (H2O2) spiking study was performed to determine the forced oxidation impact on soluble high molecular weight and low molecular weight species, charge species, and particulate formation in the presence of varying levels of free methionine and / or EDTA over a timescale of up to 3 days. Timepoints for the study were at 0, 1, and 3 days. Sample configuration was 500 µL in HPLC Max Recovery Vial. Samples were stored in a small cryobox, protected from light, left on benchtop at ambient conditions until quenching. Samples contained H2O2, Met, EDTA, surfactant, and Chimeric Canine Mab A v2; SEQ IDAttorney Reference No. 2920951-538977NOs: 24 and 25: 0.01% H2O2; 0, 2, or 5 mM L-Methionine; 0 or 0.5 mM EDTA, and 0.02%w / v Polysorbate-20 or Poloxamer-188 (see Table 13). Using a quench method, IOOJIL of 300mM Methionine in 20 mM Histidine + 8%w / v Sucrose pH 7.2 Buffer were added to 500p. L of sample. After quenching the samples were stored at -80°C until analysis to further halt the oxidation reaction. The quenching method was determined by adding enough methionine quench solution so that the final vial would contain 50pM of fresh Methionine to halt the oxidative reaction of the remaining H2O2. Controls were formulations prepared without H2O2and respective volume replaced by additional QS buffer. The control samples were also vialed and "quenched" by addition of excess methionine (lOOgL of quench solution to 500p. L of sample) to standardize the relative dilution of the samples and immediately protected from light and frozen at -80°C. Results of the study showed that oxidative stress does not lead to particulate formation in the presence of poloxamer-188, and that polysorbate-20 generates high particulate levels in the presence of H2O2in the absence of EDTA. Results of the study also showed that polysorbate-20 degradation leads to insoluble protein aggregates, and that addition of 2 mM or 5 mM methionine reduces aggregate increase from control to +0.31% and +0.11% respectively.Table 13.HydrogenPeroxide Excipient Combo EDTA Formulation Surfactant Type Methionine Spiking Study1 1 F4 Polysorbate-20 2 0.5 2 2 0.5F6 Polysorbate-20 03 3 Polysorbate-20 5 0 4 4 Polysorbate-20 5 0.50 5 5 F7 Polysorbate-20 06 6 Poloxamer-188 0 0.5 7 7 F3 Poloxamer-188 2 0.50 8 8 F3 No Antioxidant Poloxamer-188 09 9 Poloxamer-188 5 0 10 10 Poloxamer-188 2 0 11 11 Poloxamer-188 5 0.5Attorney Reference No. 2920951-538977

[0277] Example 17: Preparation of Chimeric canine antibodies Mab A and Mab B

[0278] Structural analysis of canine parvovirus and feline parvovirus complexed with antibody fragments from eight different neutralizing monoclonal antibodies were reported in Hafenstein S., et al, J Virol. 2009 Jun, 83(11):5556-66. Incomplete amino acid sequence information was provided for rat Mab E and Mab F Fab fragments, which exhibited canine parvovirus neutralization in an in vitro assay. The incomplete amino acid sequences for the variable heavy chain and variable light chain of Mab E are SEQ ID NOs. 81 and 82, respectively. The incomplete amino acid sequences for the variable heavy chain and variable light chain of Mab F are SEQ ID NOs. 83 and 84, respectively.

[0279] Three-dimensional protein structure analysis was performed to construct a redesigned first framework region for both heavy and light chains of Mab E and Mab F. The amino acid sequences of the heavy and light chain of redesigned monoclonal antibodies, designated Mab A and Mab B, are SEQ ID NO: 20 (Mab A heavy chain), SEQ ID NO: 22 (Mab A light chain), SEQ ID NO: 62 (Mab B heavy chain), and SEQ ID NO: 64 (Mab B light chain).

[0280] DNA sequences encoding a chimeric antibody were designed for fusions of Mab A VH (SEQ ID NO: 20) and Mab B VH (SEQ ID NO: 62) to canine constant IgG-B heavy chain and Mab A VL (SEQ ID NO: 22) and Mab B LC (SEQ ID NO: 64) to canine constant κ light chain resulting in SEQ ID NO: 23 (Chimeric A HC IgG-B), SEQ ID NO: 66 (Chimeric B HC IgG-B), SEQ ID NO: 25 (Chimeric A LC K), and SEQ ID NO: 68 (Chimeric B LC K). The heavy chain and light chain nucleotide sequences were synthesized chemically and inserted into an expression vector suitable for transfection into a mammalian host cell. Following transfection of heavy and light chain vector pairs into cells and culture, antibodies were affinity purified from the culture media using CaptivA® Protein A Affinity Resin (Repligen). The purified Chimeric Canine Mab A and Mab B antibodies were confirmed by SDS-PAGE analysis (data not shown).

[0281] Chimeric antibodies may also be designed and prepared based on fusions of Mab A VH (SEQ ID NO: 20) and Mab B VH (SEQ ID NO: 62) to canine constant IgG-A, IgG-C, and IgG-D heavy chains.

[0282] Example 18: Safety and Efficacy of CPMA in Kittens

[0283] Male and female kittens aged 12 to 14 weeks were administered caninized parvovirus monoclonal antibody (CPMA) in frozen or liquid form to observe any systemic or localized adverse events to the CPMA. For this example, a caninized parvovirus monoclonalAttorney Reference No. 2920951-538977antibody (CPMA) comprising SEQ ID NO: 24 and SEQ ID NO: 25 (CDR-H1 comprising SEQ ID NO: 4, CDR-H2 comprising SEQ ID NO: 5, CDR-H3 comprising SEQ ID NO: 6, CDR-L1 comprising SEQ ID NO: 13, CDR-L2 comprising SEQ ID NO: 14, and CDR-L3 comprising SEQ ID NO: 15) was utilized.

[0284] The ability of the antibody found in serum to neutralize both Feline Panleukopenia Virus (FPV) and Canine Parvovirus (CPV) was monitored by serum draws. Kittens used in the study had previously been Vaccinated against Bordetella bronchiseptica and were repurposed from the previous study. Kittens were randomly assigned to a Group such that, previous study treatment, litters and gender are distributed across all groups as evenly as possible as shown in Table 14.Table 14.Treatment Number Route Dose1Dosing Volume Schedule Group 1 Frozen24 IV 0.2 mL / kg SDO CPMAGroup 2 Frozen24 IV 0.2 mL / kg SDO and CPMA SD3 Group 3 Liquid34 IV 0.2 mL / kg SDO CPMAGroup 4 Liquid34 sc 0.2 mL / kg SDOCPMACPMA: Canine Parvovirus monoclonal antibody; IV: Intra-venous; SC: Sub-cutaneous; SD: Study Day'Material concentration - Frozen: 32.2 mg / mL (6.44 mg / kg); Liquid: 31.9 mg / mL (6.38 mg / kg)2Frozen: CPMA in PBS3Liquid: CPMA in Sucrose / Histidine and Poloxamer 188

[0285] Daily clinical observation for General Health and Injection site reaction (ISR) and Rectal temperature (RT) from Serum Draw-1 (SD-1) through SD14 was conducted for all kittens. A comparative SDO (preimmunization), observation and RT measurement before and 4 hours (+ / -30min.) post-dosing were taken. A SD3 was only for Group 2, observation and RT before and 4 hours (+ / -30min.) post-dosing. The pyrexia cutoff was greater than or equal to 103.5°F, shown in Table 15.Table 15.Treatment General ISR RThealthGroup 1 Frozen IV, 1 dose Normal None NormalAttorney Reference No. 2920951-538977Group 2 Frozen IV, 2 Normal None Cat 3 and 10, SD3 + 4 hours RT:doses 103.6°F and 104.1°F respectively.Resolved the following day Group 3 Liquid IV, 1 dose Normal None NormalGroup 4 Liquid SC, 1 dose Normal None NormalISR: Injection Site Reaction; RT: Rectal Temperature

[0286] Serum Neutralization of CPV

[0287] An analysis for CVP neutralization by serum drawn from CPMA treated animals was conducted on serum draws SD-0, SD-1, SD-4, SD-7, and SD-14 for all kittens. An analysis on SD-3 for Group 2 only was also conducted. The analysis measured serum antibody titers to neutralize canine parvovirus (CPV). Serial dilutions of heat-inactivated sera were mixed with equal volumes of CPV viral suspension (50 to 300 fluorescent antibody infective dose at 50%, FAID50) and analyzed in a cellular viral infection assay (FIG. 25A). The mixtures were incubated at 36 ±2°C for 90 ± 30 minutes prior to conducting the cell infection assay. In the assay 2.0 x 104DK2502 cells were added to the each well of 96-well microtiter plates then the antibody- virus mixture was added. Plates were incubated at 36 ±2°C, humidified, 5 +2 % CO2 incubator for 5 ± 1 days. Plates were fixed, and virus detected by specific immunofluorescence. A failure to detect the virus by immunofluorescence indicated the presence of serum neutralizing antibodies. To determine serum neutralization of antibody titers, 50% neutralization endpoints were calculated according to Reed and Muench method. Results of the assay are shown in Table 16.

[0288] Serum Neutralization of FPV

[0289] An analysis for FVP neutralization by serum drawn from CPMA treated animals was conducted on serum draws SD-0, SD-1, SD-4, SD-7, and SD-14 for all kittens. An analysis on SD-3 for Group 2 only was also conducted. The assay measured the ability of the serum to neutralize FPV. Serial dilutions of heat-inactivated sera were mixed with equal volumes of FPV viral suspension (50 to 300 FAID50) and analyzed from in a cellular viral infection assay (FIG. 25B). The mixtures were incubated at 36 ±2°C for 60 ± 15 minutes prior to conducting the cell infection assay. In the assay 2.0 x 104DK2502 cells were added to the each well of 96-well microtiter plates then the antibody-virus mixture was added.Plates were incubated at 36 ±2°C, humidified, 5 +2 % CO2 incubator for 5 ±1 days. Plates were fixed, and virus detected by specific immunofluorescence. Failure to detect the virus by immunofluorescence indicates the presence of serum neutralizing antibodies. The infectionAttorney Reference No. 2920951-538977results shown in FIG. 25B are similar to the infection results shown in FIG. 25A in terms of the infection rate verses the virus concentration, indicating that the antibodies have similar neutralizing activities against either CPV or FPV.Attorney Reference No. 2920951-538977Table 16: CPV Serum Neutralization Assay ResultsGroup Treatment Cat ID SDO SD 0 + 4hr SD 1 SD3 SD3 + SD4* SD7 SD 144hr*1 Frozen IV, 1 dose 7 < 8 1024 1448 512 NA NA 512 512 1 Frozen IV, 1 dose 12 < 8 1024 2048 1024 NA NA 724 724 1 Frozen IV, 1 dose 13 < 8 724 512 724 NA NA 724 724 1 Frozen IV, 1 dose 16 < 8 1448 724 1024 NA NA 1024 512 2 Frozen IV, 2 doses 2 < 8 1024 724 1448 2048 1448 2048 512 2 Frozen IV, 2 doses 3 < 8 1448 512 724 1448 1024 1448 512 2 Frozen IV, 2 doses 4 < 8 724 1448 1024 1024 1448 2048 724 o 2 Frozen IV, 2 doses 10 < 8 1448 1024 1024 1024 2048 2048 1024 o3 Liquid IV, 1 dose 1 < 8 2048 1448 724 NA NA 724 512 3 Liquid IV, 1 dose 5 < 8 1024 1024 1024 NA NA 724 362 3 Liquid IV, 1 dose 8 < 8 1448 1024 724 NA NA 724 < 8 3 Liquid IV, 1 dose 15 < 8 724 1024 724 NA NA 724 724 4 Liquid SC, 1 dose 6 < 8 512 724 1448 NA NA 1024 362 4 Liquid SC, 1 dose 9 < 8 362 1024 724 NA NA 512 181 4 Liquid SC, 1 dose 11 < 8 724 724 724 NA NA 724 512 4 Liquid SC, 1 dose 14 < 8 512 1024 512 NA NA 724 128*Samples collected only on cats that received their second dose on SD2; NA: Not applicable

Claims

Attorney Reference No. 2920951-538977WHAT IS CLAIMED:

1. A method of treating parvo viral infection in a feline, comprising:administering to the feline a canine antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV).

2. The method of claim 1, wherein the antibody binds to feline panleukopenia virus (FPV).

3. The method of any one of claims 1 - 2, wherein the antibody binds to canine parvovirus and feline panleukopenia virus.

4. The method of any one of claims 1 - 3, wherein the antibody binds to canine parvovirus and / or feline panleukopenia virus with a dissociation constant (Kd) of less than 5 x 10'6M, less than 1 x 10'6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10'8M, less than 1 x 10'8M, less than 5 x 10'9M, less than 1 x 10'9M, less than 5 x IO10M, less than 1 x IO'10M, less than 5 x 10'11M, less than 1 x 10"11M, less than 5 x 10'12M, or less than 1 x IO'12M.

5. The method of any one of claims 1 -4, wherein the antibody binds to canine parvovirus and / or feline panleukopenia virus with a Kd of between 5 x 10'6M and 1 x 10"6M, between 5 x 10'6M and 5 x 10'7M, between 5 x 10'6M and 1 x 10’7M, between 5 x 10'6M and 5 x 10'8M, between 5 x 10'6M and 1 x IO"8M, between 5 x 10'6M and 5 x 10'9M, between 5 x 10'6M and 1 x 10'9M, between 5 x 10’6M and 5 x IO’10M, between 5 x 10'6M and 1 x IO’10M, between 5 x 10'6M and 5 x 10’11M, between 5 x 10'6M and 1 x 10’11M, between 5 x 10"6M and 5 x 10"12M, between 5 x 10"6M and 1 x 10"12M, between 1 x 10'6M and 5 x 10'7M, between 1 x 10'6M and 1 x 10'7M, between 1 x 10'6M and 5 x 10'8M, between 1 x 10'6M and 1 x 10'8M, between 1 x 10’6M and 5 x 10’9M, between 1 x 10'6M and 1 x 10‘9M, between 1 x 10‘6M and 5 x IO"10M, between 1 x 10‘6M and 1 x IO"10M, between 1 x 10"6M and 5 x 10"11M, between 1 x 10"6M and 1 x 10"11M, between 1 x 10"6M and 5 x 10'12M, between 1 x 10'6M and 1 x 10'12M, between 5 x 10'7M and 1 x 10’7M, between 5 x 10'7M and 5 x 10'8M, between 5 x 10’7M and 1 x 10’8M, between 5 x 10'7MAttorney Reference No. 2920951-538977and 5 x IO’9M, between 5 x 10'7M and 1 x 10'9M, between 5 x 10'7M and 5 x 10'10M, between 5 x 10‘7M and 1 x IO"10M, between 5 x 10‘7M and 5 x IO"11M, between 5 x 10‘7M and 1 x IO’11M, between 5 x 10'7M and 5 x IO’12M, between 5 x 10'7M and 1 x IO’12M, between 1 x 10'7M and 5 x 10'8M, between 1 x 10'7M and 1 x IO'8M, between 1 x 10'7M and 5 x IO’9M, between 1 x 10'7M and 1 x 10'9M, between 1 x 10'7M and 5 x 10'10M, between 1 x 10'7M and 1 x 10'10M, between 1 x 10'7M and 5 x 10'11M, between 1 x 10'7M and 1 x IO’11M, between 1 x 10'7M and 5 x 10’12M, between 1 x 10'7M and 1 x 10’12M, between 5 x 10"8M and 1 x IO"8M, between 5 x IO’8M and 5 x IO'9M, between 5 x 10'8M and 1 x IO’9M, between 5 x IO'8M and 5 x IO'10M, between 5 x IO'8M and 1 x IO'10M, between 5 x 10'8M and 5 x IO'11M, between 5 x 10'8M and 1 x IO'11M, between 5 x 10'8M and 5 x 10’12M, between 5 x IO'8M and 1 x 10’12M, between 1 x IO'8M and 5 x 10’9M, between 1 x 10"8M and 1 x 10"9M, between 1 x IO’8M and 5 x IO’10M, between 1 x 10'8M and 1 x 10'10M, between 1 x IO'8M and 5 x IO’11M, between 1 x IO'8M and 1 x IO’11M, between 1 x IO'8M and 5 x 10'12M, between 1 x 10'8M and 1 x 10'12M, between 5 x 10'9M and 1 x IO"9M, between 5 x 10‘9M and 5 x IO"10M, between 5 x 10‘9M and 1 x IO"10M, between 5 x 10"9M and 5 x IO"11M, between 5 x 10"9M and 1 x IO"11M, between 5 x 10"9M and 5 x 10'12M, between 5 x 10'9M and 1 x 10’12M, between 1 x 10'9M and 5 x IO’10M, between 1 x 10'9M and 1 x IO'10M, between 1 x 10'9M and 5 x 10'11M, between 1 x 10'9M and 1 x IO’11M, between 1 x 10'9M and 5 x 10’12M, between 1 x 10'9M and 1 x 10’12M, between 5 x IO"10M and 1 x IO’10M, between 5 x IO’10M and 5 x IO'11M, between, 1 x IO'10M and 5 x IO'11M, between 1 x IO'10M and 1 x IO'11M, between 1 x IO’10M and 5 x 10"12M, between 1 x IO'10M and 1 x 10'12M, between 5 x IO'11M and 1 x 10’12M, between 5 x IO’11M and 5 x 10'12M, between 5 x IO'11M and 1 x 10'12M, between 1 x IO’11M and 5 x IO’12M, or between 1 x IO"11M and 1 x 10’12M.

6. The method of any one of claims 1 - 5, wherein the antibody comprises:(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5, (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 6, and (b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 15.

7. The method of any one of claims 1 - 6, wherein the antibody comprises:Attorney Reference No. 2920951-538977(a) (i) a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 7 or 8, (ii) a HC-FR2 comprising the amino acid sequence of SEQ ID NO: 9, (iii) a HC-FR3 comprising the amino acid sequence of SEQ ID NO: 10, (iv) a HC-FR4 comprising the amino acid sequence of SEQ ID NO: 11 or 12, and(b) (i) a LC-FR1 comprising the amino acid sequence of SEQ ID NO: 16, (ii) a LC-FR2 comprising the amino acid sequence of SEQ ID NO: 17, (iii) a LC-FR3 comprising the amino acid sequence of SEQ ID NO: 18, and (iv) a LC-FR4 comprising the amino acid sequence of SEQ ID NO: 19.

8. The method of any one of claims 1 - 7, wherein the antibody comprises:a variable heavy chain sequence of SEQ ID NO: 20, 21, 85, or 86; anda variable light chain sequence of SEQ ID NO: 22 or 87.

9. The method of any one of claims 1 - 8, wherein the antibody comprises:a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 23, 24, 37, or 38; anda light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25 or 39.

10. The method of any one of claims 1 - 9, wherein the antibody comprises:a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 24; anda light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25.

11. The method of any one of claims 1 - 5, wherein the antibody comprises:(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 42, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 43, (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 44, and (b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53, and (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 54.Attorney Reference No. 2920951-53897712. The method of claim 11, wherein the antibody comprises:(a) (i) a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 45 or 46, (ii) a HC-FR2 comprising the amino acid sequence of SEQ ID NO: 47 or 48, (iii) a HC-FR3 comprising the amino acid sequence of SEQ ID NO: 49 or 50, (iv) a HC-FR4 comprising the amino acid sequence of SEQ ID NO: 51, and (b) (i) a LC-FR1 comprising the amino acid sequence of SEQ ID NO: 55 or 56, (ii) a LC-FR2 comprising the amino acid sequence of SEQ ID NO: 57, (iii) a LC-FR3 comprising the amino acid sequence of SEQ ID NO: 58 or 59, and(iv) a LC-FR4 comprising the amino acid sequence of SEQ ID NO: 60 or 61.

13. The method of any one of claims 11 - 12, wherein the antibody comprises:a variable heavy chain sequence of SEQ ID NO: 62, 63, or 88; anda variable light chain sequence of SEQ ID NO: 64, 65, or 89.

14. The method of any one of claims 11 - 13, wherein the antibody comprises:a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 66, 67, or 79; anda light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 68, 69, or 80.

15. The method of any one of claims 1 - 14, wherein the antibody is incorporated into a composition comprising:a) a buffering agent;b) an isotonic agent; andc) a surfactant.

16. The method of claim 15, wherein the buffering agent comprises one or more of histidine and / or citrate.

17. The method of any one of claims 15 or 16, wherein the isotonic agent comprises one or more of mannitol, sorbitol, maltitol, glycerol, sucrose, glucose, dextrose, levulose, fructose, lactose, polyethylene glycols 400 to 4000, phosphates, sodium chloride, potassium chloride, calcium chloride, calcium glucono-glucoheptonate, or dimethyl sulfone.Attorney Reference No. 2920951-53897718. The method of any one of claims 15 - 17, wherein the surfactant comprises poloxamer-188 and / or polysorbate-20.

19. The method of any one of claims 15 - 18, wherein the composition further comprises a chelating agent.

20. The method of claim 19, wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA).

21. The method of any one of claims 15 -20, wherein the composition further comprises at least one additional antioxidant.

22. The method of claim 21, wherein the at least one additional antioxidant is methionine.

23. The method of any one of claims 15 -22, wherein the composition further comprises a preservative.

24. The method of claim 23, wherein the preservative comprises one or more of: benzalkonium chloride, benzoic acid, benzyl alcohol, benzyl benzoate, boric acid, chlorobutanol, parabens (such as methylparaben and propylparaben), phenol, sodium sorbate, potassium sorbate, sodium benzoate, sorbic acid, thimerosal, sulfur dioxide, sulfites, nitrites, nitrates, lactic acid, propionic acid, propionates, phosphoric acid, ascorbic acid, sodium ascorbate, butylated hydroxytoluene, butylated hydroxyanisole, gallic acid, sodium gallate, tocopherols, citric acid, citrates, tartaric acid, and / or lecithin.

25. The method of any one of claims 15 -24, wherein the composition does not comprise sodium chloride (NaCl).

26. The method of any one of claims 15 -25, the composition is administered by a subcutaneous route.

27. The method of any one of claims 1 - 26, wherein the antibody is administered in an amount in the range of 0.01 mg / kg body weight to 100 mg / kg body weight per dose, in theAttorney Reference No. 2920951-538977range of 0.5 mg / kg body weight to 100 mg / kg body per dose, in the range of 1 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 5 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 10 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 20 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 50 mg / kg body weight to 100 mg / kg body weight per dose, in the range of 1 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 5 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 0.5 mg / kg body weight to 10 mg / kg body weight per dose, in the range of 0.01 mg / kg body weight to 0.5 mg / kg body weight per dose, in the range of 0.01 mg / kg body weight to 0.1 mg / kg body weight per dose, or in the range of 5 mg / kg body weight to 50 mg / kg body weight per dose.

28. The method of any one of claims 1 - 27, wherein the antibody is administered at least once per week, at least twice per week, at least thrice per week, at least four times per week, at least five times per week, at least six times per week, or at least seven times per week.

29. The method of any one of claims 1 - 28, wherein the antibody is administered at least two consecutive weeks, at least three consecutive weeks, at least four consecutive weeks, at least five consecutive weeks, at least six consecutive weeks, at least seven consecutive weeks, at least eight consecutive weeks, at least nine consecutive weeks, at least ten consecutive weeks, at least eleven consecutive weeks, or at least twelve consecutive weeks.

30. The method of any one of claims 15 -29, wherein the antibody or composition comprises:a) the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) a buffering agent in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition; andd) an surfactant in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition.

31. The method of any one of claims 15 - 29, wherein:Attorney Reference No. 2920951-538977the buffering agent is histidine;the isotonic agent is sucrose; andthe surfactant is poloxamer-188.

32. The method of any one of claims 15 -31, wherein the composition further comprises a pharmaceutically acceptable carrier.

33. The method of claim 32, wherein the pharmaceutically acceptable carrier is phosphate buffered saline (PBS).

34. The method of any one of claims 15 -33, wherein the antibody is present in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), or about 0.5% to about 5% (w / v) relative to the total weight of the composition.

35. The method of any one of claims 15 - 34, wherein the antibody is present in an amount of about 10 mg / ml to about 50 mg / ml, 15 mg / ml to about 45 mg / ml, 20 mg / ml to about 40 mg / ml, 25 mg / ml to about 35 mg / ml, 10 mg / ml to about 20 mg / ml, or 28 mg / ml to about 32 mg / ml.

36. The method of any one of claims 15 - 35, wherein the buffering agent is present in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), or about 0.40% (w / v) to about 0.6% (w / v) relative to the total weight of the composition.

37. The method of any one of claims 15 -36, wherein the isotonic agent is present in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), about 2% to about 15% (w / v), about 3% to about 10%, about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition.

38. The method of any one of claims 1 - 14, wherein the antibody is incorporated into a composition comprising phosphate buffered saline (PBS).

39. A composition, comprising:Attorney Reference No. 2920951-538977a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), wherein the antibody is present in an amount of about 0.01% to about 0.5% (w / v), about 0.1% to about 0.5% (w / v), about 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) a buffering agent, wherein the buffering agent is present in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent, wherein the isotonic agent is present in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10%, about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) a surfactant, wherein the surfactant is present in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% to about 0.3% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

40. A composition, comprising:a) an antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV), wherein the antibody is present in an amount of about 10 mg / ml to about 50 mg / ml, 15 mg / ml to about 45 mg / ml, 20 mg / ml to about 40 mg / ml, 25 mg / ml to about 35 mg / ml, 10 mg / ml to about 20 mg / ml, or 28 mg / ml to about 32 mg / ml;b) a buffering agent, wherein the buffering agent is present in an amount of about 0.10% (w / v) to about 1.0% (w / v), about 0.20% (w / v) to about 0.8% (w / v), about 0.40% (w / v) to about 0.6% (w / v), or about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) an isotonic agent, wherein the isotonic agent is present in an amount of about 0.1% to about 20% (w / v), about 1% to about 20% (w / v), of about 2% to about 15% (w / v), about 3% to about 10%, about 5% to about 10% (w / v), about 6% to about 10% (w / v), about 6% to about 9% (w / v), about 6% to about 8% (w / v), about 7% to about 8% (w / v), or about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) a surfactant, wherein the surfactant is present in an amount of about 0.01% to about 5% (w / v), about 0.01% to about 2% (w / v), about 0.05% to about 0.5% (w / v), about 0.01% toAttorney Reference No. 2920951-538977about 0.3% (w / v), about 0.01% to about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

41. The composition of any one of claims 39 - 40, wherein the composition is stable and / or shelf-stable for more than about one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, two years, three years, or four years or more.

42. The composition of any one of claims 39 -41, wherein the composition is stable and / or shelf-stable for more than about one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, two years, three years, or four years or more at about 2 - 8°C.

43. The composition of any one of claims 39 - 42, wherein the composition is stable or shelf-stable for about twelve months at an antibody concentration of about 10 mg / ml to about 50 mg / ml, 15 mg / ml to about 45 mg / ml, 20 mg / ml to about 40 mg / ml, 25 mg / ml to about 35 mg / ml, 10 mg / ml to about 20 mg / ml, or 28 mg / ml to about 32 mg / ml at 2 - 8°C.

44. The composition of any one of claims 39 - 43, wherein the composition comprises:a) the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) the buffering agent in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) the isotonic agent in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition; andd) the surfactant in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition.

45. The composition of any one of claims 39 - 44, wherein:the buffering agent is histidine;the isotonic agent is sucrose; andthe surfactant is poloxamer-188.Attorney Reference No. 2920951-53897746. The composition of any one of claims 39 - 45, further comprises methionine as an additional antioxidant.

47. The composition of claim 46, wherein the composition comprises:a) the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) histidine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) methionine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;d) sucrose in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition; ande) poloxamer-188 in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition.

48. The composition of any one of claims 46 - 47, wherein the composition comprises:a) the antibody that binds to canine parvovirus (CPV) and / or feline panleukopenia virus (FPV) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition;b) histidine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;c) methionine in an amount of about 0.01% to about 5.0% (w / v) relative to the total weight of the composition;d) sucrose in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition;e) poloxamer-188 in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition; andf) ethylenediaminetetraacetic acid (EDTA) in an amount of about 0.1% to about 10% (w / v) relative to the total weight of the composition.

49. The composition of any one of claims 39 - 48, wherein the composition further comprises a pharmaceutically acceptable carrier.Attorney Reference No. 2920951-53897750. The composition of claim 49, wherein the pharmaceutically acceptable carrier is phosphate buffered saline (PBS).

51. The composition of any one of claims 39 - 50, wherein the composition reduces particulate formation and / or subvisible particulate formation, where the particulates are smaller than about 1μm, 10μm, or 25μm.

52. The composition of any one of claims 39 - 51, wherein the composition comprises less than about 100, less than about 200, less about 500, or less than about 1000 particles (particle / mL) after about 50 days, 60 days, 70 days, 80 days, 100 days, or 120 days.

53. The composition of claim 52, wherein the particles have a size from about 1 μm to 10μm.

54. The composition of claim 52, wherein the particles have a size from about 10μm to 25 μm.

55. The composition of any one of claims 39 - 54, wherein a storage temperature is at about 2 - 8°C.

56. The composition of any one of claims 39 - 55, wherein the antibody comprises:(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5, (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 6, and (b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 15.

57. The composition of any one of claims 39 - 56, wherein the antibody comprises:(a) (i) a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 7 or 8, (ii) a HC-FR2 comprising the amino acid sequence of SEQ ID NO: 9, (iii) a HC-FR3 comprising the amino acid sequence of SEQ ID NO: 10, (iv) a HC-FR4 comprising the amino acid sequence of SEQ ID NO: 11 or 12, andAttorney Reference No. 2920951-538977(b) (i) a LC-FR1 comprising the amino acid sequence of SEQ ID NO: 16, (ii) a LC-FR2 comprising the amino acid sequence of SEQ ID NO: 17, (iii) a LC-FR3 comprising the amino acid sequence of SEQ ID NO: 18, and (iv) a LC-FR4 comprising the amino acid sequence of SEQ ID NO: 19.

58. The composition of any one of claims 39 - 57, wherein the antibody comprises: a variable heavy chain sequence of SEQ ID NO: 20, 21, 85, or 86; anda variable light chain sequence of SEQ ID NO: 22 or 87.

59. The composition of any one of claims 39 - 58, wherein the antibody comprises: a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 23, 24, 37, or 38; anda light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25 or 39.

60. The composition of any one of claims 39 - 59, wherein the antibody comprises: a heavy chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 24; anda light chain sequence at least 95%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 25.

61. The composition of any one of claims 39 - 60, wherein the composition provides passive immunity against infection with canine parvovirus (CPV) and / or feline panleukopenia virus (FPV).

62. Use of the composition of any one of claims 39 - 61 to treat feline panleukopenia virus (FPV), wherein the composition provides passive immunity against infection with canine parvovirus (CPV) and / or feline panleukopenia virus (FPV).

63. A method of treating parvo viral infection in a feline, comprising administering to the feline a composition of any of claims 39 - 61 in an amount effective to treat a parvoviral infection in a feline.Attorney Reference No. 2920951-53897764. The method of claim 63, wherein the antibody in the composition binds to feline panleukopenia virus (FPV).

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