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. 2920951-483977 PARVOVIRUS ANTIBODY FORMULATIONS AND METHODS FOR VETERINARY USE CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is an International (PCT) patent application which claims priority to U. S. Provisional Patent Application No. 63 / 748,686, filed 23 January 2025, the entire contents of which are incorporated herein by reference.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] A Sequence Listing in XML format, submited under 37 C. F. R. §§ 1.831-1.835, entitled 2920951-483977 Sequence Listing.xml, 101,318 bytes in size, generated on January 15, 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 and / or feline parvovirus. Compositions described herein further provide for improved shelf-life, and stability, and robustness under a variety of conditions. Compositions described herein further provide for passive immunity against infection with a canine or feline parvovirus and / or treating parvoviral infection in companion animals, such as dogs and cats.BACKGROUND

[0004] 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, Gertrude 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 incubationAttorney Reference No. 2920951-483977 period, CPV targets rapidly dividing cells of the body including bone marrow, lymphocytes and intestinal crypt epithelial cells.

[0005] 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.

[0006] 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. 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.

[0006] 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.SUMMARY

[0007] In an aspect, the disclosure provides for compositions comprising antibodies that bind to or are capable of binding to canine parvovirus and / or feline parvovirus; a buffering agent; an isotonic agent; and a surfactant. In aspects, compositions described herein result in improved stability, and shelf-life. In other aspects, compositions described herein result in improved stability, and shelf-life, and robustness.Attorney Reference No. 2920951-483977

[0008] 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.

[0009] 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.

[0010] In aspects, compositions described herein comprise a canine K light constant region or a feline K light constant region.

[0011] 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.

[0012] In a further aspect, antibodies described herein that bind to canine parvovirus and / or feline parvovirus comprising:(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.

[0013] 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.

[0014] In a further aspect, the antibody that binds to canine parvovirus and / or feline parvovirus comprises a heavy chain sequence at least 95% identical to SEQ ID NO: 24 and a light chain sequence at least 95% identical to SEQ ID NO: 25. In a further aspect, the antibody that binds to canine parvovirus and / or feline parvovirus comprises a heavy chain sequence at least 98% identical to SEQ ID NO: 24 and a light chain sequence at least 98% identical to SEQ ID NO: 25. In a further aspect, the antibody that binds to canine parvovirus and / or feline parvovirus comprises a heavy chain sequence at least 99% identical to SEQ ID NO: 24 and a light chain sequence at least 99% identical to SEQ ID NO: 25. In yet a further aspect, the antibody that binds to canine parvovirus and / or feline parvovirus comprises a heavy chain sequence is 100% identical to SEQ ID NO: 24 and a light chain sequence 100% identical to SEQ ID NO: 25.Attorney Reference No. 2920951-483977

[0015] In others aspect, the antibody that binds to canine parvovirus and / or feline parvovirus comprises a heavy chain sequence comprises SEQ ID NO: 24 and a light chain sequence comprises SEQ ID NO: 24, 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.

[0016] In a further aspect, the animal is a companion animal, such as a dog or cat. In aspects, compositions herein may be used to both selectively treat dogs, cats, or both dogs and cats. In aspects, the same composition may be used to treat dogs and cats.

[0017] 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.

[0018] In an aspect, the buffering agent comprises histidine and / or citrate.

[0019] 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, dimethyl sulfone. In preferred embodiments, the isotonic agent comprises sucrose.

[0020] In an aspect, the surfactant comprises poloxamer-188 and / or polysorbate-20.

[0021] 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.

[0022] In an aspect, compositions described herein are suitable for injection to the companion animal. In aspects, 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, 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.

[0023] 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, compositions described herein are administered in two or three doses. In further aspects,Attorney Reference No. 2920951-483977 compositions described herein are administered in two or three doses over the course of one, two, or three months.

[0024] 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.

[0025] In an aspect, the antibody that binds to canine parvovirus and / or feline parvovirus 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.

[0026] 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.

[0027] 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.

[0028] 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%, 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.

[0029] 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), 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.

[0030] In a further aspect, the disclosure provides for a pharmaceutical composition comprising, consisting essentially of, or consisting of an administrable solution comprising: a) an antibody that binds to canine parvovirus and / or feline parvovirus; b) a buffering agent; c) an isotonic agent; and d) a surfactant.Attorney Reference No. 2920951-483977

[0031] In an aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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%, 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), 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.

[0032] 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 0.10% (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%, 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), 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.Attorney Reference No. 2920951-483977

[0033] 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%, 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), 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.

[0034] In a further aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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%, 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), about 0.01% toAttorney Reference No. 2920951-483977 about 0.3% (w / v), or about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

[0035] In a further aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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 0.001% to about 10% (w / v) relative to the total weight of the composition.

[0036] In another aspect, the disclosure provides for compositions comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus and / or feline parvovirus in an amount of from about 1 mg / ml to about 50 mg / ml;b) histidine in an amount of from about 10 rnM 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).

[0037] In another aspect, the disclosure provides for a composition comprising, consisting essentially of, or consisting of:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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).

[0038] 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 and / or feline parvovirus in an amount of about 25 mg / rnL to 35 mg / mL;Attorney Reference No. 2920951-483977 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).

[0039] 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 and / or feline parvovirus in an amount of 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 tnM;d) sucrose in an amount of about 8% (w / v); ande) poloxamer-188 in an amount of about 0.02% (w / v).

[0040] 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 and / or feline parvovirus in an amount of 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 tnM;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.

[0041] In aspects, antibodies described herein that bind to canine parvovirus and / or feline parvovirus comprise CDR chains from SEQ ID NO: 4, 5, 6, 13, 14, and 15. In another aspects, antibodies described herein that bind to canine parvovirus and / or feline parvovirus 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.

[0042] In aspects, antibodies described herein are monoclonal antibodies. In additional aspects, compositions described herein comprise monoclonal antibodies.

[0043] 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. In other aspects, compositions described herein are stable at about 6 months or more, about 9 months or more, er about 12 months or more, or about 18 months or more at about 2°C - 8°C.

[0044] In other aspects, compositions comprising antibodies that bind to canine parvovirus and / or feline parvovirus 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 additional aspects, compositions comprising antibodies that bind to canine parvovirus and / orAttorney Reference No. 2920951-483977 feline parvovirus in an amount of about 30 mg / mL concentration are stable at about 6 months or more, about 9 months or more, ef about 12 months are more, or about 18 months or 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 or more at about 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, er about 12 months ormore, or about 18 months or more at about 2°C -8°C.

[0045] In aspects, the disclosure provides for compositions comprising antibodies that bind to canine parvovirus and / or feline parvovirus, wherein the composition is stable and / or shelfstable 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, eighteen months, two years, three years, or four years or more at about 2°C - 8°C.

[0046] In aspects, the disclosure provides for compositions comprising antibodies that bind to canine parvovirus and / or feline parvovirus, wherein the composition is stable or shelf-stable for about twelve months or about eighteen 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 for about twelve months or about eighteen 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.Attorney Reference No. 2920951-483977

[0047] 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. The disclosure further provides for methods of improving stability and / or robustness 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 and / or robustness 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 and / or robustness of parvovirus compositions described herein compared to buffers comprising phosphate at the same pH. In aspects, buffers described herein comprise histidine and not phosphate.

[0048] 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. In further aspects, buffers comprising histidine and buffers comprising citrate improve stability and / or robustness 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 and / or robustness 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.

[0049]

[0050] 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.

[0051] In aspects, compositions described herein reduce particulate formation and / or subvisible particulate formation. In further aspects, compositions described herein withAttorney Reference No. 2920951-483977 poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through six months of shelflife.

[0052] In aspects, compositions described herein reduce particulate formation and / or subvisible particulate formation, where the particulates are smaller than about 1pm, 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 25 pm. 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 1 µm to 10 µm or about 10pm to 25pm, after about 50 days, 60 days, 70 days, 80 days, 100 days, or 120 days. In aspects, the storage temperature is at 2 - 8° C.

[0053] In further aspects, Formulation 3 (F3) has reduced particulate formation and / or subvisible particulate formation, wherein the particulates are smaller than about 1pm, 10pm, or 25pm as compared to Formulation 4 (F4) as set forth in Table 7. In further aspects, Formulation 3 (F3) described herein reduces particulate formation and / or subvisible particulate formation, where the particulates are aboutl pm to 10pm or about 10pm to 25 pm as compared to Formulation 4 (F4) as set forth in Table 7. In further aspects, Formulation 3 (F3) described herein comprises less than about 100, less than about 200, less about 500, or less than about 1000 particles (particle / mL), wherein the particles have a size from about 1 µm to 10 µm and / or about 10pm to 25pm, after about 50 days, 60 days, 70 days, 80 days, 100 days, or 120 days as compared to Formulation 4 (F4) as set forth in Table 7. In aspects, the storage temperature is at 2 - 8° C.

[0054] 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.

[0055] In aspects, compositions described herein comprising poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through 6 months of shelflife. 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, or more than eighteen 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, or more than eighteen months.Attorney Reference No. 2920951-483977

[0056] In aspects, compositions described herein exhibit improved robustness after at least 72 hours of agitation.

[0057] In aspects, compositions described herein exhibit improved robustness after at least 5 freeze-thaw cycles.

[0058] In aspects, compositions described herein do not contain PBS.

[0059] In a further aspect, the disclosure provides for a method for treatment of a parvoviral infection in a companion animal, the method comprising administering to the companion animal 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 and / or feline parvovirus; b) a buffering agent; c) an isotonic agent; and d) a surfactant.

[0060] In an aspect, the disclosure provides for methods for treatment of a parvoviral infection in a companion animal, the method comprising administering to the companion animal a therapeutically effective amount of a composition comprising, consisting essentially of, or consisting of: a) an antibody that binds to canine parvovirus and / or feline parvovirus; b) a buffering agent; c) an isotonic agent; and d) a surfactant.

[0061] 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.

[0062] In an aspect, the disclosure provides for compositions described herein that provides passive immunity against infection with canine or feline parvovirus and / or treating parvoviral infection in a companion animal. Antibodies described herein may be used in compositions described herein.

[0063] 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.

[0064] In aspects, antibodies and compositions described herein are administered parenterally or subcutaneously.

[0065] 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.

[0066] 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 or feline parvovirus.Attorney Reference No. 2920951-483977

[0067] The disclosure further provides for administering antibodies and compositions described herein after infection with the canine or feline parvovirus.

[0068] In further aspects, antibodies and compositions described herein are administered after the subject, for example a companion animal such as a dog or cat, has exhibited at least one symptoms selected from fever, vomiting, diarrhea, lymphopenia, and septicemia.

[0069] In aspects, antibodies and compositions described herein are administered after canine or feline parvovirus has been detected in feces, such as determined by a positive cageside SNAP test. In aspects, the subject has previously been administered a parvovirus vaccine.

[0070] In aspects, the subject, for example a companion animal or dog or cat, has not previously been administered a parvovirus vaccine. In further aspects, the subject, for example a companion animal such as a dog or 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 companion animal such as a dog or cat, is hand-reared, the subject’s mother does not produce milk, or the subject is unable to produce antibodies against parvovirus.

[0071] In further aspects, the subject, for example a companion animal such as a dog or cat, is living in an environment contaminated with the canine or feline parvovirus.BRIEF DESCRIPTION OF THE DRAWINGS

[0072] FIG. 1 depicts stability of canine parvovirus in different buffer systems.

[0073] FIG. 2, FIG. 3, and FIG. 4 depicts the results of SEC monomer testing for canine parvovirus antibody compositions with or without stabilizing excipients.

[0074] FIG.5 and FIG. 6 depicts particulate formation during freeze / thaw cycles in canine parvovirus antibody compositions using MFI assays.

[0075] FIG. 7 evaluates canine parvovirus antibody compositions with various excipient combinations using a cIEF assay. Canine parvovirus antibody formulations F1-F8 are described in Table 7.

[0076] FIG. 8 depicts fragmentation of canine parvovirus in compositions with various excipient combinations using a CE-SDS assay. Canine parvovirus antibody formulations F1-F8 are described in Table 7.

[0077] FIGs. 9 and 10 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 7.Attorney Reference No. 2920951-483977

[0078] FIGs. 11, 12, and 13 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 7.

[0079] FIGs. 14 and 15 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 7.

[0080] FIGs. 16, 17, and 18 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 7.

[0081] FIGs. 19 and 20 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.

[0082] FIGs. 21 and 22 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.

[0083] FIG. 23 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an SEC-HPLC assay after 18 months at 2-8 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0084] FIG. 24 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using a cIEF assay after 18 months at 2-8 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0085] FIG. 25 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an nrCE-SDS assay after 18 months at 2-8 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0086] FIG. 26 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an rCE-SDS assay after 18 months at 2-8 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0087] FIG. 27 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using background membrane imaging to evaluate subvisible particulates after 18 months at 2-8 °C. Canine parvovirus antibodyAttorney Reference No. 2920951-483977 Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0088] FIG. 28 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an SEC-HPLC assay after 9 months at 5 °C and 25 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0089] FIG. 29 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using a cIEF assay after 9 months at 5 °C and 25 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0090] FIG. 30 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an nrCE-SDS assay after 9 months at 5 °C and 25 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0091] FIG. 31 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using an rCE-SDS assay after 9 months at 5 °C and 25 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0092] FIG. 32 depicts the results of a stability study of canine parvovirus antibody in compositions with various excipient combinations using background membrane imaging to evaluate subvisible particulates after 9 months at 5 °C and 25 °C. Canine parvovirus antibody Formulation 1 is described in Table 3, Formulation 2 is described in Table 4, and Formulation 3 is described in Table 5.

[0093] FIG. 33 depicts graphical representations of the assays (agitation, freeze-thaw, background membrane imaging) used in stress testing to evaluate formulation robustness in Example 11.

[0094] FIG. 34 depicts the results of a stress-test study of canine parvovirus antibody in compositions with various excipient combinations using background membrane imaging to evaluate subvisible particulates after 72 hours of agitation. Canine parvovirus antibody formulations FR1-FR13 are described in Table 12.

[0095] FIG. 35 depicts the results of a stress-test study of canine parvovirus antibody in compositions with various excipient combinations using background membrane imaging to evaluate subvisible particulates after 5 freeze-thaw cycles. Canine parvovirus antibody formulations FR1-FR13 are described in Table 12.Attorney Reference No. 2920951-483977

[0096] In each of Figures 1 - 22, the canine parvovirus described comprises Chimeric Canine Mab A v2 (SEQ ID NOs: 24 and 25).DESCRIPTION OF CERTAIN SEQUENCES

[0097] 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 A5 VMWNDGDTS Variable heavy chain CDR-H2 of Mab A6 PELPGLTYGVWFPY Variable heavy chain CDR-H3 of Mab A7 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 chainCDR-L1 of Mab AAttorney Reference No. 2920951-483977 KASNRNT Variable light chain CDR-L2 of Mab A MQSTSYPLTF Variable light chain CDR-L3 of Mab A DIVMTQTPASMSISVGDRVTMNC 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 AGSGTKLEIK Variable light chain framework region LC-FR4 of Mab A OKOZXE'SGPGLVOPSOTLSLTCTVSGFSLSSYHVH Variable heavy chain of WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL Mab A SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG LTYGVWFPYWGQGTLVTVSS (Mab A HC) QKQZXESGPGLVAPSOTLSLTCTVSGFSLSSYHVH Variable heavy chain of WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL Mab A variant 2 SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG LTYGVWFPYWGQGTLVTVSA HC-FR1 Q13AHC-FR4 S11A (MabAHCv2) D / VMTQSPTSMSISVGDRVTMNCKASQNVDSNV 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 VVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT QESLSHSPGK OKOZXESGPGLVAPSOTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRL chain of Mab A v2 and SISRDTSKSQVFFKMSSLQTEDTATYYCARPELPG canine IgG-B LTYGVWFPYWGQGTLVTVSAASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG HC-FR1 Q13A VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN HC-FR4 S11AVAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPAttorney Reference No. 2920951-483977 EMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR (Chimeric A HC v2 IgG-B) VVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI 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 MAVLGLLLCLVTFPSCVLSOKQZKE'SGPGLVOPSO 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) DTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGK QMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLK GKQFTCKVNNKALPSPIERTISKARGQAHQPSVYV LPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ RGDTFICAVMHEALHNHYTQESLSHSPGK MAVLGLLLCLVTFPSCVLS OKOZKE. SGPGLVAPSO 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 DTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGK QMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLK (Chimeric A HC v2 IgG-B GKQFTCKVNNKALPSPIERTISKARGQAHQPSVYV with leader) LPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ RGDTFICAVMHEALHNHYTQESLSHSPGK METDTLLLWVLLLWVPGSTGDIVMTQTPASMSIS Chimeric variable light VGDRVTMNCKASQNVDSNVDWYQQKTGQSPNL chain of Mab A and canineLTYKASNRNTGVPDRFTGSGSGTDFTFTISNMQAEAttorney Reference No. 2920951-483977 DLAVYYCMQSTSYPLTFGSGTKLEIKRNDAQPAV K light constant region with YLFQPSPDQLHTGSASWCLLNSFYPKDINVKWK leader sequence 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 CNVAHPPSNTKVDKTVRKTOHPPGPKPCDCPKCP PPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLG PDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYR WSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTIS KAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSF HPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQ KSLTQSPGK DZEA / T’gT’PASMSISVGDRVTMNCKASQNVDSNVD Chimeric variable light WYQQKTGQSPNLLIYKASNRNTGVPDRFTGSGSG chain of Mab A and feline K TDFTFTISNMQAEDLAVYYCMQSTSYPLTFGSGT light constant region KLEIKRSDAQPSVFLFQPSLDELHTGSASIVCILND FYPKEVNVKWKVDGWQNKGIQESTTEQNSKDS (Chimeric A LC K) TYSLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLV KSFNRSECQREZ>7EM7’g77’ASMSISVGDRVTMNCKASQNVDSNVD 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 VMWNDGDTSYNLAVKGRFTISRDNAKNTLYLQM canine IgG-B with leader NSLRAEDTAVYYCARPELPGLTYGVWFPYWGQG sequence TLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACL VSGYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLY SLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKP (Chimeric A HC v3 IgG-B VPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPK with leader) PKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDG KQMQTAKTQPREEQFNGTYRWSVLPIGHQDWL KGKQFTCKVNNKALPSPIERTISKARGQAHQPSVY VLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNG QQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRW QRGDTFICAVMHEALHNHYTQESLSHSPGK QVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV Caninized variable heavy HWVRQPPGKGLEWVAVMWNDGDTSYNLAVKG chain of Mab A v3 RFTISRDNAKNTLYLQMNSLRAEDTAVYYCARPE LPGLTYGVWFPYWGQGTLVTVSS MAVLGLLLCLVTFPSCVLSEVQLVESGGDLVKPG Caninized variable heavyGTLRLSCTVSGFSLSSYHVHWVRQPPGKGLEWLG chain of Mab A v4 andAttorney Reference No. 2920951-483977 VMWNDGDTSYNLAVKGRFTISRDNAKNTLYFQM canine IgG-B with leader NSLRAEDTATYYCARPELPGLTYGVWFPYWGQG sequence TLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACL VSGYFPEPVTVSWNSGSLTSGVHTFPSVLQSSGLY (Caninized A HC v4 IgG-B SLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKP with leader) VPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPK PKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDG KQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWL 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) EFVMTQSPASLSLSQEEKVTITCKASQNVDSNVD 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 HYTQESLSHSPGK EVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHV 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 LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIEAttorney Reference No. 2920951-483977 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHN HYTQESLSHSPGK EIVMTQSPASLSLSQEEKVTITCKASQNVDSNVD Caninized variable light WYQQKPGQAPKLLIYKASNRNTGVPSRFSGSGSG chain of Mab A and canine TDFSFTISSLEPEDVAVYYCMQSTSYPLTFGQGTK K light constant region LEKRNDAQPAVYLFQPSPDQLHTGSASWCLLNS FYPKDINVKWKVDGVIQDTGIQESVTEQDKDSTY(Caninized A LC K) SLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQ RSECQRVD QLTLRESGPGLVKPSQSLSLTCTVSGFSLSSYHVH Felinized variable heavy WTRQRPGRGLEWLGVMWNDGDTSYAFQGRISIT chain of Mab A ADTAQNQFSLQLSSMTTDDTAVYYCARPELPGLT YGVWFPYWGQGALVTVS (Felinized A HC) 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 gKgZXESGPGLVQPSQTLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab B ePeZXE'SGPGLVQPSETLSLTCTVS Variable heavy chain framework region HC-FR1 of Mab B variant 2 (v2) Q16E WVRQPPGKGLEWIG Variable region heavy chain framework region HC-FR2 of Mab B 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)H2NAttorney Reference No. 2920951-483977R8KS15TL21FM34IF36YWGQGTLVIVS 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 / KMTgTPSLLSASVGDRVTLNC 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) S3PGAGTKLELK Variable light chain framework region LC-FR4 of Mab BGAGTKLEIK Variable light chain framework region LC-FR4 of Mab B variant 2 (v2) L8I gFgZXESGPGLVQPSQTLSLTCTVSGFSLTSYGVS Variable heavy chain of WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLS Mab B ISRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPG YNLRGWFVYWGQGTLVTVS (Mab B HC) 0P0ZXESGPGLVQPSE1ESLTCTVSGFSLTSYGVS Variable heavy chain ofWVRQPPGKGLEWMGTMWNDGDTDYNSALRSKL Mab B variant 2Attorney Reference No. 2920951-483977 SISRDTSKSQVFLKMNSLQTEDTAIYYCARSQLPG YNLRGWFVYWGQGTLVIVS HC-FR1 Q16EHC-FR2 I13MHC-FR3 H2NHC-FR3 R8KHC-FR3 S15THC-FR3 L21FHC-FR3 M34IHC-FR3 F36Y(Mab B HC v2) n / KMT’gTT’SLLSASVGDRVTLNCKASHNINKNLE 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) grgZKE'SGPGLVQPSQTLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLS chain of Mab B and canine ISRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPG IgG-B YNLRGWFVYWGQGTLVIVSASTTAPSVFPLAPSC GSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGV(Chimeric B HC IgG-B) HTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDP EDPEVQISWFVDGKQMQTAKTQPREEQFNGTYR VVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT QESLSHSPGKgFeZKE'SGPGLVQPSETLSLTCTVSGFSLTSYGVS 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 H2NHC-FR3 R8KPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRAttorney Reference No. 2920951-483977 VVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTI HC-FR3 S15T SKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKD HC-FR3 L21F FFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSY HC-FR3 M34I FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYT HC-FR3 F36Y QESLSHSPGK(Chimeric B HC v2 IgG-B) D / FA / FgT’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) MAVLGLLLCLVTFPSCVLSgFgZATESGPGLVQPSQ Chimeric variable heavy TLSLTCTVSGFSLTSYGVSWVRQPPGKGLEWIGT chain of Mab B and canine MWNDGDTDYHSALRSRLSISRDSSKSQVLLKMNS IgG-B with leader sequence LQTEDTAMYFCARSQLPGYNLRGWFVYWGQGTL VIVSASTTAPSVFPLAPSCGSTSGSTVALACLVSGY (Canine chimeric B HC with FPEPVTVSWNSGSLTSGVHTFPSVLQSSGLYSLSS leader) MVTVPSSRWPSETFTCNVAHPASKTKVDKPVPKR ENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDT LLIARTPEVTCVWDLDPEDPEVQISWFVDGKQM QTAKTQPREEQFNGTYRWSVLPIGHQDWLKGK QFTCKVNNKALPSPIERTISKARGQAHQPSVYVLP PSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQ EPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQR GDTFICAVMHEALHNHYTQESLSHSPGK MAVLGLLLCLVTFPSCVLSgKQZXESGPGLVQPSE Chimeric 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 H2NHC-FR3 R8KAttorney Reference No. 2920951-483977 MQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKG HC-FR3 S15T KQFTCKVNNKALPSPIERTISKARGQAHQPSVYVL HC-FR3 L21F PPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQ HC-FR3 M34I QEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQ HC-FR3 F36Y RGDTFICAVMHEALHNHYTQESLSHSPGK(Canine chimeric B HC v2 IgG-B with leader) METDTLLLWVLLLWVPGSTGn / n / TgTPSLLSAS Chimeric variable light VGDRVTLNCKASHNINKNLEWYQQKLGEAPKLLI chain of Mab B and canine YYANNLQTGISSRFSGSGSGTDYTLTISSLQPEDV K light constant region with ATYYCYQYNSGHTFGAGTKLELKRNDAQPAVYL leader sequence FQPSPDQLHTGSASWCLLNSFYPKDINVKWKVD GVIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLS(Canine chimeric B LC HELYSCEITHKSLPSTLIKSFQRSECQRVD Kwith leader) METDTLLLWVLLLWVPGSTGDIOMTOSPPVLSAS 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 K with leader) gKgZXE'SGPGLVQPSQTLSLTCTVSGFSLTSYGVS 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 SLTQSPGKn / EMTgTPSLLSASVGDRVTLNCKASHNINKNLE Chimeric variable light WYQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGT chain of Mab B and feline K DYTLTISSLQPEDVATYYCYQYNSGHTFGAGTKL light constant region ELKRSDAQPSVFLFQPSLDELHTGSASIVCILNDFY PKEVNVKWKVDGWQNKGIQESTTEQNSKDSTY(Feline chimeric B LC K)Attorney Reference No. 2920951-483977 SLSSTLTMSSTEYQSHEKFSCEVTHKSLASTLVKS FNRSECQREn / KMTgTPSLLSASVGDRVTLNCKASHNINKNLE 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 sequence FQPSPDQLHTGSASWCLLNSFYPKDINVKWKVD GVIQDTGIQESVTEQDKDSTYSLSSTLTMSSTEYLS 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 lightYQQKPGQPPKLLIYYANNLQTGVPARFSGSGSGT chain of Mab B v3Attorney Reference No. 2920951-483977 DYSLNIHPMEEDDTAMYYCYQYNSGHTFGGGTK LEIK EIVLTQSPASLAVSLGQRATISCKASHNINKNLEW Caninized variable light YQQKPGQPPKLLIYYANNLQTGVPARFSGSGSGT chain of Mab B v3 and DYSLNIHPMEEDDTAMYYCYQYNSGHTFGGGTK canine K light constant LEIKRNDAQPAVYLFQPSPDQLHTGSASWCLLNS region FYPKDINVKWKVDGVIQDTGIQESVTEQDKDSTY SLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQ(Caninized B LC v3 RSECQRVD K) GPGLVQPSQTLSLTCTVSGFSLSSYHVHWVRQPP Mab E variable HC GKGLEWLGVMWNDGDTSYNLALNSRLSISRDTS KSQVFFKMSSLQTEDTATYYCARPELPGLTYGVW FPYWGQGTLVTVS ASMSISVGDRVTMNCKASQNVDSNVDWYQQKT Mab E variable LC GQSPNLLIYKASNRNTGVPDRFTGSGSGTDFTFTIS NMQAEDLAVYYCMQSTSYPLTFGSGTKLEIKRA GPGLVQPSQTLSLTCTVSGFSLTSYGVSWVRQPPG Mab F variable HC KGLEWIGTMWNDGDTDYHSALRSRLSISRDSSKS QVLLKMNSLQTEDTAMYFCARSQLPGYNLRGWF VYWGQGTLVTVS SLLSASVGDRVTLNCKASHNINKNLEWYQQKLGE Mab F variable LC APKLLIYYANNLQTGISSRFSGSGSGTDYTLTISSL QPEDVATYYCYQYNSGHTFGAGTKLELKRA MWQLVSSTALLLLVSAGTQAADVPKAVWLEPK Exemplary canine CD 16 WNRVLTMDSVTLKCQGDHLLRDNYTWLHNGRPI with linker, and poly-His SNQISTYIIKNASIKNSGEYRCQTDQSKLSDPVQLE VHTGWLLLQVPRLVFQEGELIQLKCHSWKNTPVR NVQYFQNGRGKKFFYNNSEYHIPAATSEHNGSYF CRGIIGKKNESSEAVNIIIQGSSLPSTSLLLSHWPQG 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 PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCVW Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPI ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutantAttorney Reference No. 2920951-483977 DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGK S10E PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWD Exemplary variant canine LDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGT IgG-B Fc YRWSVLPIGHQDWLKGKQFTCKVNNKALPSPDE RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI CD 16 enhancing binding KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED mutant 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 LKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10DI103D PAPEMLGGPDVFIFPPKPKDTLLIARTPEVTCWV Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPE ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10DI103E PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCVW Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPD ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10EI103D PAPEMLGGPEVFIFPPKPKDTLLIARTPEVTCVW Exemplary variant canine DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPE ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTC CD 16 enhancing binding LIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEmutant DGSYFLYSKLSVDKSRWQRGDTFICAVMHEALH NHYTQESLSHSPGKS10EI103EAttorney Reference No. 2920951-483977DESCRIPTION OF CERTAIN EMBODIMENTS

[0098] Compositions comprising antibodies that bind canine parvovirus and / or feline parvovirus are provided. In addition, antibodies, heavy chains, and light chains comprising one or more complementary determining regions (CDRs) are provided. Polynucleotides encoding antibodies to canine parvovirus and / or feline parvovirus are provided. Methods of producing or purifying antibodies to canine parvovirus and / or feline parvovirus 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 canine parvovirus and / or feline parvovirus are provided.

[0099] 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.

[0100] 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. In 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

[0101] Antibodies directed against parvovirus are provided, for example antibodies that bind to canine parvovirus and / or feline parvovirus. Parvovirus antibodies provided herein include, but are not limited to, monoclonal antibodies, chimeric antibodies, caninized antibodies, and felinized antibodies.

[0102] 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 8-11), 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 acidAttorney Reference No. 2920951-483977 sequences of the variable heavy chain and variable light chain of Mab B are provided (SEQ ID NOs: 62 and 64, respectively).

[0103] 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.

[0104] 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, amino 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.

[0105] 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 antigen-binding activity. Canine, feline, and equine species have different varieties (classes) of antibodies that are shared by many mammalians.

[0106] 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 antibodyAttorney Reference No. 2920951-483977 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.

[0107] 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, the 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.

[0108] 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 typicallyAttorney Reference No. 2920951-483977 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.

[0109] In some embodiments, the monoclonal antibody is a Mab A, Mab A v2, Mab B, or Mab B v2.

[0110] “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.

[0111] “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 (panleukopenia virus).

[0112] 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 beAttorney Reference No. 2920951-483977 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 residues involved 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.

[0113] 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.

[0114] 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-Hl, 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.

[0115] 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 toAttorney Reference No. 2920951-483977 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 A. The various CDRs within an antibody can be designated by their appropriate number and chain type, including, without limitation as CDR-H1, CDR-H2, CDR-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.

[0116] Table A 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 ALoop 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 atAttorney Reference No. 2920951-483977

[0117] 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 acid sequence 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.

[0118] 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.

[0119] 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.

[0120] 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.

[0121] 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,Attorney Reference No. 2920951-483977 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: 14 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: 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.

[0122] 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.

[0123] 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 mayAttorney Reference No. 2920951-483977 comprise a variable heavy chain having the following structure: (CDR-H1)-(HC-FR2)-(CDR-H2)-(HC-FR3)-(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).

[0124] 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.

[0125] 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.

[0126] 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, SEQ ID NO: 81, or SEQ ID NO: 83.

[0127] 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 chain sequence of SEQ ID NO:Attorney Reference No. 2920951-483977 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.

[0128] 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, CHI, CH2, and CH3. Nonlimiting exemplary heavy chain constant regions include y, 8, a, E, and p. Each heavy chain constant region corresponds to an antibody isotype. For example, an antibody comprising a y constant region is an IgG antibody, an antibody comprising a 8 constant region is an IgD antibody, an antibody comprising an a constant region is an IgA antibody, an antibody comprising a p constant region is an IgM antibody, and an antibody comprising an £ constant region is an IgE antibody. Certain isotypes can be further subdivided into subclasses. For example, IgG antibodies include, but are not limited to, IgGl (comprising a yi constant region), IgG2 (comprising a y2 constant region), IgG3 (comprising a y3 constant region), and IgG4 (comprising a y4 constant region) antibodies; IgA antibodies include, but are not limited to, IgAl (comprising an ai constant region) and IgA2 (comprising an 012 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 X and K. 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.

[0129] 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 chimeric antibody comprises at least one mouse variable region and at least one feline constant region. In some embodiments, all of the variableAttorney Reference No. 2920951-483977 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.

[0130] 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).

[0131] 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 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); (b) (i) a heavy chain amino acid sequence at least 90%, at leastAttorney Reference No. 2920951-483977 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).

[0132] 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 aAttorney Reference No. 2920951-483977 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.

[0133] 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.

[0134] 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.

[0135] In some embodiments, a parvovirus antibody comprises a feline heavy chain constant region selected from an IgGl, IgG2a, and IgG2b constant region.

[0136] 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 y constant region, an a constant region, a 5 constant region, an E constant region, a. 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, Fv framework 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.

[0137] 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 theAttorney Reference No. 2920951-483977 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.

[0138] 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 y constant region, an a constant region, a 5 constant region, an s constant region, a p, constant region, or etc.) or fragment thereof. In some embodiments, a felinized antibody is an antibody fragment, such as Fab, scFv, (Fab’)i, 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.

[0139] 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.

[0140] A “fragment crystallizable polypeptide” or “Fc polypeptide” is the portion of an antibody molecule that interacts with effector molecules and cells. It comprises the C-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 performed in 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).

[0141] 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 bindAttomey Reference No. 2920951-483977 CD16. In some embodiments, a biological activity of an Fc polypeptide is the ability to bind protein A.

[0142] 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 8 chain, “IgE Fc” denotes the Fc region of an £ chain, “IgM Fc” denotes the Fc region of a p, chain, etc. In some embodiments, the IgG Fc region comprises CHI, 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 y heavy chains, such as IgG-A, IgG-B, IgG-C, or IgG-D. In some instances, IgG Fc regions are isolated from feline y 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.

[0143] The terms “IgX Fc” and “IgX Fc polypeptide” include wild-type IgX Fc polypeptides and variant IgX Fc polypeptides, unless indicated otherwise.

[0144] 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 IgGl a 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.

[0145] 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 for acute 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.

[0146] 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-Attorney Reference No. 2920951-483977 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.

[0147] 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 wildtype or variant IgG Fc that binds to CD16. In some embodiments, a parvovirus comprises a variant IgG Fc comprising one or more afucosylated glycan.

[0148] 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.

[0149] 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.

[0150] 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 binding affinity compared to a reference polypeptide. Exemplary variant IgG Fc polypeptides having increased CD16 binding affinity are disclosed in US20220267414Al(e.g., Example 2), which is incorporated by reference herein in its entirety.

[0151] 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; Q an aspartic acid or a glutamic acid at position 10 and / or position 103 of SEQ ID NO: 91. In some embodiments aAttorney Reference No. 2920951-483977 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.

[0152] 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.

[0153] 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, KinEx A, biolayer interferometry (BLI), or surface plasmon resonance devices.

[0154] 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 Kd of 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 binding model 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.

[0155] 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, KinEx A, biolayer interferometry (BLI), surface plasmon resonance devices, or etc.Attorney Reference No. 2920951-483977

[0156] “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)^ / z«. Biol. Clin. 51: 19-26, the contents of which is herein incorporated by reference.

[0157] “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.

[0158] 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, 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 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, 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 10'10M, 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’nM, 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, 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 10'11M, 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 10"8M, 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 IO’10M, between 1 x 10'7M and 5 x 10’11M, between 1 x 10'7M and 1 x 10’11M,Attorney Reference No. 2920951-483977 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 10"8M and 5 x 10"9M, between 5 x IO'8M and 1 x 10'9M, between 5 x 1 O'8M and 5 x 1 O'10M, between 5 x 1 O'8M and 1 x 1 O'10M, between 5 x 1 O'8M and 5 x 10"11M, between 5 x IO'8M and 1 x IO'11M, between 5 x IO'8M and 5 x 10'12M, between 5 x IO'8M and 1 x 10'12M, 1 x IO’8M and 5 x 10’9M, between 1 x 10'8M and 1 x 10'9M, between 1 x 10‘8M and 5 x IO"10M, between 1 x 10‘8M and 1 x IO"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 10"8M and 1 x 10'12M, between 5 x 10'9M and 1 x IO'9M, between 5 x IO'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 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 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, 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 10'12M, or between 1 x IO'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.

[0159] “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.

[0160] 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.

[0161] In some embodiments, a variant has at least 1, 2, 3, 4, or 5 amino acids substituted by a different amino acid.

[0162] 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% sequenceAttorney Reference No. 2920951-483977 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.

[0163] 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.

[0164] 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.

[0165] 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 2. 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 2.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; GinGiy (G) _ AlaAttorney Reference No. 2920951-483977 His (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) Vai; SerTrp (W) Tyr; PheTyr (Y) Trp; Phe; Thr; SerVal (V) Ile; Leu; Met; Phe; Ala; Norleucine

[0166] 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.

[0167] 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.

[0168] Conservative substitutions may be made in accordance with the below. 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.Conservative Amino Acid substitutionAttorney Reference No. 2920951-483977Conservative Amino Acid SubstitutionsAmino Acid Substitutions (others are known in the art)Ala Ser, Gly, CysArg Lys, Gin, HisAsn Gin, His, Glu, AspAsp Glu, Asa, GinCys Ser, Met, ThrGin Asn, Lys, Glu, Asp, ArgGin Asp, Asn, GinGly Pro, Ala, SerHis Asn, Gin, 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

[0169] 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 3, may be introduced and the products screened if needed.Amino Acid substitutionAttorney Reference No. 2920951-483977Amino Acid SubstitutionsOriginal Residue(naturallyoccurring amino Conservativeacid) Substitutions Exemplary Substitutions Ala (A) Val Val; Leu; Ile Arg (R) Lys Lys; Gln; Asn Asn (N) Gln GGln; His; Asp, Lys; Arg Asp (D) Glu Glu; AsnCys (C) Ser Ser: AlaGln (Q) Asn Asn; Glu.Glu (E) Asp Asp; GlnGly (G) Ala Ala.His (H) Arg Asn; Gln; Lys; ArgIle (I) Leu Leu; Val; Met; Ala; Phe;NorleucineLeu (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) T.hr ThrThr (T) Ser SerTrp (W) Tyr Tyr; PheTyr (Y) Phe Trp; Phe; Thr; SerVal (V) Leu Ile; Leu; Met; Phe; Ala;Norleucine

[0170] 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.

[0171] 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; fungal cells, such as yeast; plant cells; and insect cells. Nonlimiting exemplary mammalian cellsAttorney Reference No. 2920951-483977 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.

[0172] 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.

[0173] 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 non-treated 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.

[0174] 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 withinAttorney Reference No. 2920951-483977 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.

[0175] As described herein, stability is measured as no change in material attributes during shelflife while the composition meets specifications. Representative specifications may include potency, content, purity, and / or sterility. Shelf-life stability refers to no impact on efficacy or safety during the shelflife of the product. Also as described herein, robustness is measured as the ability to withstand physical stresses (for examples, agitation and freeze-thaw) that would occur during product processing and handling.

[0176] 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%, between 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%,Attorney Reference No. 2920951-483977 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%.Exemplary Pharmaceutical Compositions

[0177] 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 non-toxic 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.

[0178] 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, cat, or horse. A lyophilized composition can be reconstituted with sterile Water for Injection (WFI). Antibacterial agents (e.g., bacteriostatic reagents, such benzyl alcohol, maybe included. Thus, the invention provides pharmaceutical compositions in solid or liquid form.

[0179] 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,Attorney Reference No. 2920951-483977

[0180] 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.

[0181] 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%.

[0182] 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, the dose volume of a liquid composition of the parvovirus antibody is in a range of about 0.05 ml to about 250 ml.

[0183] In some embodiments, the compositions described herein comprise a liquid solution including a parvovirus antibody, an buffering agent, an isotonic agent, and a surfactant. In some embodiments, the buffering agent is histidine. In some embodiments, the compositions comprises 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,Attorney Reference No. 2920951-483977 polysorbate, polysorbate-20,. In preferred aspects, the surfactant comprises poloxamer-188 or polysorbate-20.

[0184] In other embodiments, the disclosure provides for compositions comprising at least one surfactant. A surfactant (also known as a surface active 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. Polyethylene 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.

[0185] 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 compositionAttorney Reference No. 2920951-483977 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%.

[0186] 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.

[0187] 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, thiolyglycolic 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..

[0188] 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),Attorney Reference No. 2920951-483977 0.005% (w / v), 0.01% (w / v), 0.015% (w / v), about 0.017% (w / v), about 0.02% (w / v), about 0.03% (w / v), about 0.04% (w / v), about 0.045% (w / v), about 0.05% (w / v), about 0.052% (w / v), about 0.055% (w / v), about 0.06% (w / v), about 0.07% (w / v), about 0.08% (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).

[0189] 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.

[0190] 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.

[0191] 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.

[0192] 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.

[0193] 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,Attorney Reference No. 2920951-483977 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.

[0194] 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, the 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.

[0195] 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).

[0196] 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%Attorney Reference No. 2920951-483977 (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).

[0197] 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.

[0198] 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.

[0199] 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

[0200] The antibodies or pharmaceutical compositions comprising the antibodies of the invention may be useful for providing passive immunity against infection with parvovirus and / orAttorney Reference No. 2920951-483977 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, dehydration, and / or secondary septicemia.

[0201] 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 more symptoms, 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.

[0202] 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.

[0203] 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 theAttorney Reference No. 2920951-483977 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.

[0204] 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 is administered 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.

[0205] 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.

[0206] 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 beAttorney Reference No. 2920951-483977 administered at least once, more than once, at least twice, at least three times, at least four times, or at least five times.

[0207] 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 five consecutive 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.

[0208] 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.

[0209] 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.

[0210] 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.

[0211] 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 someAttorney Reference No. 2920951-483977 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 determine whether the antibodies or polypeptides described herein are an appropriate treatment for the subject.

[0212] 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, synovial fluid, lymphatic tissue and epithelial cells.

[0213] 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).

[0214] 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.

[0215] 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 areAttorney Reference No. 2920951-483977 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 be employed 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 as11'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.

[0216] 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.

[0217] The following examples illustrate particular aspects of the disclosure and are not intended in any way to limit the disclosure.EXAMPLES

[0218] Example 1. Formulation Preparation

[0219] The composition presented in Table 3 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 variable regions (CDR-H1 comprising SEQ ID NO: 4, CDR-H2 comprising SEQ ID NO: 5, CDRH3 comprising SEQ ID NO: 6, CDR-L1 comprising SEQ ID NO: 13, CDR-L2 comprising SEQ ID NO: 14, and CDRL3 comprising SEQ ID NO: 15) was utilized. The amounts used are set forth in Table 3.

[0220] The composition presented in Table 4 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 CanineAttorney Reference No. 2920951-483977 Mab A v2; SEQ ID NOs: 24 and 25) was added to composition. The amounts used are set forth in Table 4.

[0221] The composition presented in Table 5 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 5.Table 3.Formulation 1Component AmountChimeric Canine Mab A v2; 30 mg / mLSEQ ID NOs: 24 and 25)Histidine 20 mMSucrose 8% w / vPoloxamer-188 0.02% w / vTable 4.Formulation 2Component AmountChimeric Canine Mab A v2; 30 mg / mL(SEQ ID NOs: 24 and 25)Histidine 20 mMMethionine 5 mMSucrose 8% w / vAttorney Reference No. 2920951-483977 Poloxamer-188 0.02% w / vTable 5.Formulation 3Component 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

[0222] Example 2. Buffer Screen

[0223] 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 (acetate, citrate, histidine, phosphate) at 20 mM buffer concentration. In addition to biophysical characterization, the different formulations were stored at 40°C to determine potential degradation pathways.

[0224] As shown in FIG. 1, 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. 2920951-483977

[0225] Example 3. Stability Testing

[0226] 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 p. L aliquot in HPLC max-recovery vials (see Table 6). 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 (see FIGs. 2-4). 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 6.Formulation Buffer Buffer pH Excipient Excipient Chimeric Canine Mab A Concentration Concentration v2; SEQ ID NOs: 24 and 25 (mM) Concentration (mg / mL) H7.2 Control Histidine 20 7.2 None N / A 15 H7.2 Sucrose Histidine 20 7.2 Sucrose 5% w / v 15 H7.2NaCl Histidine 20 7.2 NaCl 100 mM 15 H7.2Arg Histidine 20 7.2 Arginine 100 mM 15H7.2 Gly Histidine 20 7.2 Glycine 100 mM 15 H7.2 Histidine 20 7.2 Methionine 2 mM + 0.5 mM 15 MetEDTA + EDTAH7.2P188 Histidine 20 7.2 Poloxamer 0.02% w / v 15188H7.2 P520 Histidine 20 7.2 Polysorbate 0.02% w / v 1520H6.0 Control Histidine 20 6 None None 15

[0227] Example 4. Agitation Study

[0228] 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 presence of 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 lightAttorney Reference No. 2920951-483977 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 (see FIGs. 19 and 20).

[0229] Example 5. Freeze / Thaw Study

[0230] 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 (see FIGs. 5 and 6).

[0231] Example 6. Excipient Combination Study

[0232] 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 7). Formulations containing NaCl (5% Sucrose + 50 mM NaCl) have the highest rates of deamidation and fragmentation (see FIGS. 7 and 8). Results also showed that the absence of EDTA leads to significant particulate formation (see FIGs. 9 and 10), and poloxamer-188 reduced subvisible particulate formation compared to polysorbate-20.Formulations with poloxamer-188 showed significantly fewer particulates compared to formulations with polysorbate-20 through 6 months of shelflife (see FIGs. 11-15). 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 (see FIGs. 16-18).Table 7.Attorney Reference No. 2920951-483977ExcipientPoloxamerFormulation 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 for 0.5F3 7.2 8% 2 mM 0.02% oxidative degradation mM0.5 Comparison with #3 F4 7.2 8% 2 mM 0.02%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, support F7 7.2 8% 0.02%inclusion of Methionine or EDTA 0.5 Deamidation backup F8 6.0 8% 2 mM 0.02%mM

[0233] Example 7. Surfactant Study

[0234] 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 20 mM histidine buffer at pH 7.2 (see Table 8). 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 (see FIGs. 19 and 20).Table 8.Agitation Excipient Methionine Surfactant EDTAFormulation Combo Surfactant Type (mM)Level (%w / v) (mM)ID FormulationAttorney Reference No. 2920951-4839770 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 P 212-P188 F3 oloxamer-188 0.02% 0.52 13 13-P188 Poloxamer-188 0.04% 02 14 14-P188 Poloxamer-188 0.04% 0.5

[0235] Example 8. Oxidation Study with Hydrogen Peroxide

[0236] 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 ID NOs: 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 9). Using a quench method, 100µL of 300mM Methionine in 20 mM Histidine + 8%w / v Sucrose pH 7.2 Buffer were added to 500µL 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 50µM of fresh Methionine to halt the oxidative reaction of the remaining H2O2. Controls were formulations prepared without H2O2 and respective volume replaced by additional QS buffer. The control samples were also vialed and "quenched" by addition of excess methionine (100µL of quench solution to 500µL of sample) to standardize theAttorney Reference No. 2920951-483977 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 H2O2 in 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 (see FIGs. 21 and 22).Table 9.HydrogenExcipient ComboPeroxide Surfactant Type Methionine EDTA Spiking Study Formulation1 1 F4 Polysorbate-20 2 0.5 2 2 0.5F6 Polysorbate-20 03 3 Polysorbate-20 5 0 4 4 Polysorbate-20 5 0.5 5 5 F7 Polysorbate-20 0 00.5 6 6 Poloxamer-188 07 7 F3 Poloxamer-188 2 0.5 8 8 F3 No Antioxidant Poloxamer-188 0 00 9 9 Poloxamer-188 510 10 Poloxamer-188 2 0 11 11 Poloxamer-188 5 0.5

[0237] Example 9. Long-Term Stability Study

[0238] Liquid canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 30 mg / mL with 20 mM histidine buffer and various excipient combinations (Formulations 1-3 in Tables 3-5, respectively) were tested for stability at 18 months. Formulations 1-3 were sampled at 18 months at 2 — 8°C by evaluating SEC-HPLC, charge distribution (cIEF), rCE-SDS purity, nrCE-SDS purity, and subvisible particulates.

[0239] SEC-HPLC results indicated SEC monomer, aggregate, and fragment changes of less than 1% over 18 months for Formulations 1-3, indicating that oxidation risk level is low andAttorney Reference No. 2920951-483977 additional antioxidants (for example, methionine) or chelators (for example, EDTA) are not needed (see FIG. 23).

[0240] Charge distribution (cIEF) results showed an increase in acidic species of approximately 13% through 18 months for Formulations 1-3, indicating that additional excipients do not impact or decrease potential deamidation risk. Results also indicate that a change in pH would decrease deamidation over shelf-life but is not suitable to drop pH for overall stability of the antibody in the formulations (see FIG. 24).

[0241] nrCE-SDS purity results show a change in levels of fragmentation over 18 months is less than 3% for Formulations 1-3, indicating a low fragmentation risk for the antibody in these formulations (see FIG. 25).

[0242] rCE-SDS purity results show non-glycosylated heavy chain (NGHC) changes of less than 1% through 18 months for Formulations 1-3, indicating that the glycosylation pattern is stable for these formulations (See FIG. 26).

[0243] Subvisible particulates were evaluated using background membrane imaging. Results show that average subvisible particulate levels are low and do not exceed USP specifications through 18 months (see FIG. 27).

[0244] Overall results of the long-term stability study showed that the Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) was stable in Formulation 1 at 30 mg / mL drug product concentration through 18 months at 2 - 8°C.

[0245] Example 10. Liquid Stability Study

[0246] Liquid canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 30 mg / mL with 20 mM histidine buffer and various excipient combinations (Formulations 1-3 in Tables 3-5, respectively) were tested for stability in upright and inverted (upside down) positions for up to 24 months at 2 — 8°C and 6 months at 25°C. West NovaPure and Datwyler OmniFlex 3G were used as vial stoppers. Formulations were further processed by spiking in excipients (Met and or EDTA) and diluted to target antibody concentration of 20 mg / mL (see Table 10). The samples were analyzed by SEC-HPLC, nrCE-SDS, cIEF, A280, AuraPTX, ELISA and pH at 0, 1, 2, 3, 6, and 9 months, respectively.Table 10.FU1 Formulation Histidine Sucrose Methionine EDTA Poloxamer- Vial Stoppers StoragePH Volume Number (mM) (%w / v) (mM) (mM) 188 (%w / v) Size Used Orientation(mL)Attorney Reference No. 2920951-483977WestNovaPure Upright1 7.2 20 8 0.02 2R 1.2 ± 0.1Datwyler Inverted OmniFlex 3GWest Upright2 7.2 20 8 5 0.02 2R 1.2 ± 0.1NovaPure Inverted West Upright3 7.2 20 8 5 0.5 0.02 2R 1.2 ± 0.1NovaPure Inverted

[0247] SEC-HPLC results at 9 months indicated a projected monomer loss at 24 months to be less than 2% for Formulations 1-3, indicating stability in upright and inverted positions with both stoppers (West NovaPure and Datwyler OmniFlex 3G) and significantly higher monomer content and lower aggregation compared to liquid formulations not containing the histidine buffer and listed excipients (see FIG. 28).

[0248] Charge distribution (cIEF) results showed a projected increase in acidic species at 24 months of approximately 35% through 18 months for Formulations 1-3, indicating stability in upright and inverted positions with both stoppers (West NovaPure and Datwyler OmniFlex 3G) and indicating that additional excipients do not impact or decrease potential deamidation risk (see FIG. 29).

[0249] nrCE-SDS purity results show a change in levels of fragmentation over 18 months is less than 3% for Formulations 1-3, indicating stability in upright and inverted positions with both stoppers (West NovaPure and Datwyler OmniFlex 3G) and a low fragmentation risk for the antibody in these formulations (see FIG. 30).

[0250] rCE-SDS purity results show consistent non-glycosylated heavy chain (NGHC) for Formulations 1-3, indicating stability in upright and inverted positions with both stoppers (West NovaPure and Datwyler OmniFlex 3G) and indicating that the glycosylation pattern is stable for these formulations (See FIG. 31).

[0251] Subvisible particulates were evaluated using background membrane imaging. Results show no difference in particulate levels for Formulations 1-3 at 5 or 25°C and indicate stability in upright and inverted positions with both stoppers (West NovaPure and Datwyler OmniFlex 3G). Results also show that average subvisible particulate levels are low and do not exceed USP specifications (see FIG. 32).

[0252] Overall results of the liquid stability study showed that the Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) was stable in Formulation 1 at 20 mg / mL drug product concentration through 9 months at 2 - 8°C.Attorney Reference No. 2920951-483977

[0253] Example 11. Liquid Formulation Robustness / Stress Study

[0254] A robustness study was conducted to determine the quantitative ranges of excipients for liquid canine parvovirus antibody formulations (Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) at 20 mg / mL with 20 mM histidine buffer and various excipient combinations (see Tables 11 and 12). Stress testing was performed (mechanical agitation and freeze-thaw) to evaluate the robustness of the formulation to withstand physical stress (mechanical stress during fill-finish operations, freeze-thaw, agitation and shipping). The formulations were evaluated qualitatively and quantitatively through preformulation and formulation development via agitation, freeze-thaw, and background membrane imaging (see FIG. 33). Risk Impact is assigned based on the likelihood to approach stability or stress failure (see Table 13).Table 11.Formulation Antibody pH(± Histidine Sucrose Methionine EDTA Poloxamer-188 Number (mg / mL) 0.2) (mM) (%w / v) (mM) (mM) (%w / v) 1 20 7.2 20 8 N / A N / A 0.022 20 7.2 20 8 5 N / A 0.023 20 7.2 20 8 5 0.5 0.02Table 12.Storage Fin Formulation Histidine Sucrose Poloxamer- VialPH Stopper Orientation Volume Number (mM) (%w / v) 188 (%w / v) Type(Stability) (mL) WestFR1 7.4 25 9.5 0.01 2R Inverted 1.2NovaPureWestFR2 7.0 25 9.5 0.05 2R Inverted 1.2NovaPureWestFR3 7.4 15 8.0 0.01 2R Inverted 1.2NovaPureWestFR4 7.4 20 6.5 0.05 2R Inverted 1.2NovaPureWestFR5 6.6 15 6.5 0.05 2R Inverted 1.2NovaPureAttorney Reference No. 2920951-483977WestFR6 6.6 25 8.0 0.05 2R Inverted 1.2NovaPureWestFR7 6.6 20 9.5 0.01 2R Inverted 1.2NovaPureWestFR8 7.0 20 8.0 0.03 2R Inverted 1.2NovaPureWestFR9 7.4 15 9.5 0.05 2R Inverted 1.2NovaPureWestFRIO 6.6 25 6.5 0.01 2R Inverted 1.2NovaPureWestFR11 6.6 15 9.5 0.03 2R Inverted 1.2NovaPureWestFR12 7.0 15 6.5 0.01 2R Inverted 1.2NovaPureWestFR13 7.4 25 6.5 0.03 2R Inverted 1.2NovaPureTable 13.Factor Function of Factor Risk Impact Changes Target Low High ChimericCanine MabActive Low Easy 20* 15 25 Av2(mg / mL)Maintain stability andPH High Hard 7.0 6.6 7.4 solubility of activeHistidine Buffer — maintain pH,Mid Hard 20 15 25 (mM) stabilize activeTonicity modifier —Sucrose stabilizer of active,Mid Easy 8 6.5 9.5 (%w / v) protects against freezethaw stressSurfactant — protectsPoloxamer- active from interfacial High Easy 0.03 0.01 0.05 188 (%w / v)stress (agitation,Attorney Reference No. 2920951-483977 shipping, freeze-thaw,etc.)

[0255] Subvisible particulates results from agitation indicated that all formulations tested pass USP criteria after 72 hours of horizontal shaking (see FIG. 34). Subvisible particulates results from freeze-thaw indicated that subvisible particulates increase with successive freezethaw cycles and all formulations tested pass USP criteria through 5 freeze-thaw cycles (see FIG.35).

[0256] Overall results of the liquid formulation robustness / stress study showed that the Chimeric Canine Mab A v2; SEQ ID NOs: 24 and 25) was stable in the formulations tested and can withstand physical stresses (agitation and freeze-thaw) that would occur during drug product processing and handling (see Table 14).Table 14.Suitable Range to Withstand Agitation Factor Function of Factor Targetand Freeze-Thaw Stress ChimericCanine Mab A Active 20 N / Av2Maintain stability and solubilityPH 7.0 6.6 - 7.4of activeBuffer - maintain pH, stabilizeHistidine (mM) 20 15 -25activeTonicity modifier — stabilizer ofSucrose (%w / v) active, protects against freeze8 6.5 - 9.5thaw stressSurfactant — protects active fromPoloxamer-188interfacial stress (agitation, 0.03 0.01 - 0.05(%w / v)shipping, freeze-thaw, etc.)

[0257] Example 12: Preparation of Chimeric canine antibodies Mab A and Mab B

[0258] Structural analysis of canine parvovirus and feline parvovirus complexed with antibody fragments from eight different neutralizing monoclonal antibodies were reported inAttorney Reference No. 2920951-483977 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.

[0259] 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).

[0260] 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 K 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).

[0261] 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.

Claims

1. Attorney Reference No. 2920951-483977WHAT IS CLAIMED:

1. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus; b) a buffering agent;c) an isotonic agent; andd) a surfactant.

2. The composition of claim 1, wherein said 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.

3. The composition of any one of claims 1 or 2, wherein said antibody comprises a heavy chain sequence at least 95% identical to SEQ ID NO: 24 and a light chain sequence at least 95% identical to SEQ ID NO: 25.

4. The composition of any one of claims 1 - 3, wherein said antibody comprises a heavy chain sequence at least 98% identical to SEQ ID NO: 24 and a light chain sequence at least 98% identical to SEQ ID NO: 25.

5. The composition of any one of claims 1 -4, wherein said antibody comprises a heavy chain sequence at least 99% identical to SEQ ID NO: 24 and a light chain sequence at least 99% identical to SEQ ID NO: 25.

6. The composition of any one of claims 1 - 5, wherein said antibody comprises a heavy chain sequence is 100% identical to SEQ ID NO: 24 and a light chain sequence 100% identical to SEQ ID NO: 25.

7. The composition of any one of claims 1 - 6, wherein the antibody provides passive immunity against infection with canine or feline parvovirus and / or treating parvoviral infection in a companion animal.Attorney Reference No. 2920951-483977 8. The composition of claim 7, wherein the companion animal is a canine or feline.

9. The composition of any one of claims 1 - 8, wherein the buffering agent comprises histidine.

10. The composition of any one of claims 1 - 8, wherein the buffering agent comprises citrate.

11. The composition of any one of claims 1 - 10, 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.

12. The composition of claim 11, wherein the isotonic agent comprises sucrose.

13. The composition of any one of claims 1 - 12, wherein the surfactant comprises poloxamer-188 and / or polysorbate-20.

14. The composition of claim 13, wherein the surfactant comprises poloxamer-188.

15. The composition of any one of claims 1 - 14, wherein the composition comprises at least one additional antioxidant.

16. The composition of claim 15, wherein the at least one additional antioxidant is methionine.

17. The composition of any one of claims 1 - 16, wherein the composition further comprises a chelating agent.

18. The composition of claim 17, wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA).

19. The composition of any one of claims 1 - 18, wherein the composition does not comprise sodium chloride (NaCl).

20. The composition of any one of claims 1 - 19, wherein the composition is suitable for administration by a subcutaneous route.

21. The composition of any one of claims 1 - 20, 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), aboutAttorney Reference No. 2920951-483977 0.5% to about 5% (w / v), or about 0.1% to about 10% (w / v) relative to the total weight of the composition.

22. The composition of any one of claims 1 - 20, wherein the antibody is present in an amount of about 1 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.

23. The composition of any one of claims 1 - 22, 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.

24. The composition of any one of claims 1 - 23, 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.

25. The composition of any one of claims 1 - 24, 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.

26. The composition of any one of claims 1 - 25, 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.

27. The composition of any one of claims 1 - 25, 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.

28. The composition of any one of claims 1 - 27, wherein the composition is stable or shelfstable for about twelve months at an antibody concentration of about 10 mg / ml to aboutAttorney Reference No. 2920951-483977 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.

29. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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 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 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 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.

30. The composition of claim 29 comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus wherein the antibody is present in an amount of about 0.01% to about 0.5 relative to the total weight of the composition;b) a buffering agent present in an amount of about 0.10% (w / v) to about 1.0% (w / v) relative to the total weight of the composition;c) an isotonic agent present in an amount of about 7.5% to about 8.5% (w / v) relative to the total weight of the composition; andd) a surfactant present in an amount of about 0.01% to about 0.2% (w / v) relative to the total weight of the composition.

31. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus wherein the antibody is present in an amount of about 10 mg / ml to about 50 mg / ml, 15 mg / ml to aboutAttorney Reference No. 2920951-483977 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 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 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; andd) a 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.

32. The composition of any one of claims 29 - 31, wherein the antioxidant comprises methionine.

33. The composition of claim 32, wherein the buffering agent comprises histidine.

34. The composition of any one of claims 29 - 33, 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.

35. The composition of claim 34, wherein the isotonic agent comprises sucrose.

36. The composition of any one of claims 29 - 35, wherein the surfactant comprises poloxamer-188 or polysorbate-20,.

37. The composition of claim 36, wherein the surfactant comprises poloxamer-188.

38. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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;Attorney Reference No. 2920951-483977 c) sucrose in an amount of about 1% to about 20% (w / v) relative to the total weight of the composition; andd) poloxamer-188 in an amount of about 0.01% to about 0.1% (w / v) relative to the total weight of the composition.

39. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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.

40. A composition comprising:a) an antibody that binds to canine parvovirus and / or feline parvovirus 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 0.001% to about.1% (w / v) relative to the total weight of the composition.

41. The composition of any one of claims 29 - 40, wherein said antibody comprisesAttorney Reference No. 2920951-483977 (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.

42. The composition of any one of claims 29 -41, wherein said antibody comprises a heavy chain sequence at least 95% identical to SEQ ID NO: 24 and a light chain sequence at least 95% identical to SEQ ID NO: 25.

43. The composition of any one of claims 29 - 42, wherein said antibody comprises a heavy chain sequence at least 98% identical to SEQ ID NO: 24 and a light chain sequence at least 98% identical to SEQ ID NO: 25.

44. The composition of any one of claims 29 - 43, wherein said antibody comprises a heavy chain sequence at least 99% identical to SEQ ID NO: 24 and a light chain sequence at least 99% identical to SEQ ID NO: 25.

45. The composition of any one of claims 29 - 44, wherein said antibody comprises a heavy chain sequence is 100% identical to SEQ ID NO: 24 and a light chain sequence 100% identical to SEQ ID NO: 25.

46. The composition of any one of claims 1 - 45, wherein said composition is a pharmaceutical composition.

47. The composition of any one of claims 29 - 46, 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.

48. The composition of any one of claims 29 - 46, 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 2 - 8° C.

49. The composition of any one of claims 1 - 48, wherein the composition provides for reduced particulate formation 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. 2920951-483977 months, eleven months, twelve months, two years, three years, or four years or more relative to a composition that comprises an antibody that binds to canine parvovirus and / or feline parvovirus and does not comprise one or more of histidine, sucrose, and poloxamer-188.

50. The composition of any one of claims 1 - 48, wherein the composition reduces particulate formation and / or subvisible particulate formation, where the particulates are smaller than about 1 µm, 10 µm, or 25 µm.

51. The composition of any one of claims 1 -48, 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.

52. The composition of claim 51, wherein the storage temperature is at about 2 - 8° C.

53. The composition of any one of claims 51 or 52, wherein the particles have a size from about 1 µm to 10 µm.

54. The composition of any one of claims 51 or 52, wherein the particles have a size from about 10 µm to 25 µm.

55. The composition of any one of claims 29 - 54, wherein the composition provides passive immunity against infection with canine or feline parvovirus and / or treating parvoviral infection in a companion animal.

56. A method for treatment of a parvoviral infection in a companion animal, the method comprising administering to the companion animal a therapeutically effective amount of a composition of anyone of claims 1 - 55.

57. The method of claim 56, wherein said companion animal is a canine.

58. The method of claim 56, wherein said companion animal is a feline.

59. Use of a composition for treatment of a parvoviral infection in a companion animal, the method comprising administering to the companion animal a therapeutically effective amount of a composition of anyone of claims 1 - 55.

60. Use of claim 58, wherein said companion animal is a canine or feline.

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