KR101453516B1 - Composition for preventing and treating autoimmune diseases comprising anti-VEGF antibody - Google Patents

Abstract

The present invention relates to the use of an anti-VEGF antibody designated F6 for the prevention and treatment of autoimmune diseases. More specifically, the present invention relates to a method for the prevention and treatment of autoimmune diseases, And to the use for preventing and treating an autoimmune disease. Accordingly, the present invention relates to pharmaceutical compositions and methods of treatment for the prevention and treatment of autoimmune diseases comprising said anti-VEGF antibodies.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing and treating autoimmune diseases comprising an anti-VEGF antibody,

The present invention relates to the use of an anti-VEGF antibody designated F6 for the prevention and treatment of autoimmune diseases. More specifically, the present invention relates to a method for the prevention and treatment of autoimmune diseases, And to the use for preventing and treating an autoimmune disease. Accordingly, the present invention relates to pharmaceutical compositions and methods of treatment for the prevention and treatment of autoimmune diseases comprising said anti-VEGF antibodies.

The human immune system protects the body from external antigens that enter the body, but does not attack its own tissues because of its self-tolerance. However, when the self-tolerance of the immune system is destroyed and the protein normally expressed by its own gene is recognized as an object of attack and the antibody is made or the T cell reaction is caused to destroy the normal tissue, this is called autoimmunity. It is called autoimmune disease.

In the mid-1980s, Mosmann et al suggested that helper T lymphocytes (Th) could be divided into two groups of cells, Th1 and Th2, according to the cytokine secretion pattern (Mosmann TR, et al., J Immunol., 136: 2348-2357, 1986). Th1 cells then secrete IFN-γ, activate macrophages and the like, induce cellular immune responses, and Th2 cells secrete IL-4, IL-5, and the like, and are involved in the humoral immune response. In addition, it is known that excessive differentiation into Th1 due to imbalance of Th1 and Th2 cells leads to inflammatory autoimmune disease. However, there has been a question about the Th1 / Th2 paradigm when mice deficient in IFN-? Or IFN receptors have been reported to cause autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (Infante-Duarte C, et al., J In IL-12 and IL-23 studies, IL-23-induced Th17 cells are more important than Th1 cells in causing autoimmune disease (Murphy, J. Immunol., 165: 6107-6115, 2000) Langrish CL, et al., J Exp Med 201 (2002), < RTI ID = 0.0 > 2): 233-40, 2005)

Th17 cells have been so named because they secrete IL-17 cytokines and are independent of Th1 or Th2. Recently, the transcription factor of Th17 cell, RORγt, has been identified and the signaling system and transcription process of Th17 cell have been identified. In addition, Th17 cells, unlike Th1, Th2, and Treg (regulatory T cell) cells, are involved at the forefront of the inflammatory response seen in autoimmune diseases, thereby maximizing the signal of the inflammatory response and accelerating the progress of the disease. Accordingly, the development of a therapeutic agent for an autoimmune disease targeting the inhibition of Th17 cell activity has been greatly emphasized.

Specifically, Th17 is associated with psoriasis (Wilson, NJ, et al., Nat Immunol, 8 (9): 950-957, 2007; Arican, O., et al., Mediators Inflamm, 2005 (5) 2005; Wolk, K., et al., Eur J Immunol, 36 (5): 1309-1323, 2006; Chan, JR, et al., J Exp Med, 203 (12): 2577-2587, 2006) (10): 977-986, 2007; Mathur et al., ≪ RTI ID = 0.0 > , JH Immunol, 178 (8): 4901-4907, 2007), systemic sclerosis (Zhou, L., et al., 8 (9): 967-974, 2007; Distler, JH, et Lupus, 9 (8): 589-593, 2000; Kang, HK, et al., J et al., 52 (3): 856-864, 2005), systemic lupus erythematosus Immunol, 178 (12): 7849-7858, 2007), multiple sclerosis (Matusevicius, D., et al., Mult Scler, 5 (2): 101-104, 1999; Vaknin-Dembinsky, A., et al. J Immunol, 176 (12): 7768-7774, 2006), autoimmune myocarditis (Rangachari, M., et al., J Exp Med, 203 (8): 2009-2019, 2006; Sonderegger, I., et al., Eur J Immunol, 36 (11): 2849-2856, 2006), asthma Barczyk, A., et al., Respir Med, 97 (6): 726-733, 2003; S. Al et al., Immunol, 108 (3): 430-438, Bullens, D. M., et al., Respir Res, 7: 135, 2006; Ahn, et al., Curr Opin Allergy Clin Immunol, 7 (5) (1998)], atopic dermatitis and contact hypersensitivity (Wong, CK, et al., Clin Exp Immunol, 125 (2): 177-183, Immunity, 17 (3): 375-387, 2002; He, D., et al., J Immunol, 177 (10): 6852-6858, 2006), inflammatory bowel disease (Burakoff, R., et al., Inflamm Bowel Dis, 12 (7): 558-565, 2006; Billich, A., IDrugs, 10 (1): 53-59, 2007; Caviglia , Et al., World J Gastroenterol, 13 (39): 5238-5244, 2007; Wada, Y., et al., Blood, 109 (3): 1156-1164, 2007) J Periodontol, 75 (1): 37-43, 2004; Takahashi, K., et al., J Oral Microbiol Immunol, 18 (1): 30-36, et al., J Clin Periodontol, 32 (4): 383-389, 2005), and these autoimmune It has been reported as a therapeutic target of the disease.

Currently, immunosuppressants that block the signal transduction pathway in T cells are the most commonly used therapeutic agents for autoimmune diseases. However, these immunosuppressants are toxic, infection, lymphoma, diabetes, tremor, headache, diarrhea, hypertension, There is a problem that a side effect such as a renal failure occurs. Therefore, there is a need to develop a new therapeutic agent for immune diseases which has no side effects, is inexpensive, and has excellent therapeutic effect.

In the previous study, 14 strains of human antibodies specifically binding to VEGF were obtained from recombinant VEGF from a phage library prepared from human-derived scFv library cells in the previous study (Korean Patent Publication No. 10-2010-0059374) Screening and identifying its structure. In addition, it was confirmed that the anti-VEGF antibodies bind to VEGF with high affinity to human and mouse, and inhibit VEGF-induced capillary-like tube formation in vascular endothelial cells, and these antibodies are inhibited by VEGF overexpression, As a treatment for vascular diseases.

Accordingly, the inventors of the present invention have further studied the physiological function of the antibody named F6 in the anti-VEGF antibody. As a result, the F6 antibody inhibits the differentiation of Th17 cells, and thus has an excellent effect for the treatment of an autoimmune disease associated with Th17 Thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising an anti-VEGF antibody named F6.

It is another object of the present invention to provide a method for treating an autoimmune disease comprising administering a pharmaceutical composition comprising the antibody.

In one aspect, the present invention provides a pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising an anti-VEGF antibody designated F6.

Preferably, the antibody comprises a heavy chain variable region comprising a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 5, a heavy chain CDR2 having the amino acid sequence SEQ ID NO: 6, and a heavy chain CDR3 having the amino acid sequence SEQ ID NO: 7; And a light chain variable region comprising a light chain CDR1 having the amino acid sequence of SEQ ID NO: 8, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 9, and a light chain CDR3 having the amino acid sequence of SEQ ID NO:

Preferably, the antibody is a monoclonal antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 3.

As used herein, the term "antibody" refers to an immunoglobulin molecule that is immunologically reactive with a particular antigen, and may be obtained by genetic engineering, such as chimeric, humanized, human and heterologous binding antibodies Includes produced forms. In addition, the term "antibody" in the present invention includes not only a whole antibody form, but also a functional fragment of an antibody molecule. Generally, an antibody is a structure having two full-length light chains and two full-length heavy chains, and each light chain is linked to a heavy chain by a disulfide bond. In the present invention, the antibody includes a functional fragment of an antibody molecule having an antigen-binding function. Examples of the fragment include Fab, Fab ', F (ab') 2, Fd, Fv, dAb, scFv, Or bispecific molecules, diabodies, triabodies, tetrabodies, and the like.

As used herein, the term "variable region " means a region that specifically binds to an antigen in the antibody, and CDR1, CDR2, and CDR3, which are complementary determining regions, exist in the variable region, respectively. A framework region (FR) portion exists between the CDRs to support the CDR ring.

The antibody of the present invention is characterized by specifically binding to VEGF. In a specific example of the present invention, the binding strength was measured using a Langmuir 1: 1 binding model. As a result, it was confirmed that the binding strength of F6 to VEGF was higher than that of the known anti-VEGF antibody, Avastin ).

The antibody of the present invention can be produced by a general method known in the art, for example, a genetically recombinant method. For example, reference can be made to the production method described in Korean Patent Publication No. 10-2010-0059374. The above patent documents are incorporated herein by reference in their entirety.

As described in the Background of the Invention, the presence of Th17, which belongs to the auxiliary T lymphocyte (Th) and is independent of Th1 or Th2, has been reported, and Th17 cells induced by IL-23 It is more important to cause immune diseases. Th17 cells are involved at the forefront of the inflammatory response seen in autoimmune diseases, thereby maximizing the signal of the inflammatory reaction, accelerating the progression of the disease, and capable of developing a therapeutic agent for autoimmune diseases by targeting the inhibition of Th17 cell activity.

The inventors of the present invention firstly confirmed that F6 antibody can be used as a therapeutic agent for autoimmune diseases associated with Th17 cells by inhibiting the differentiation of Th17 cells. In a specific example of the present invention, type II collagen was injected into DBA1 / J mice at 7 weeks of age to construct an animal model of rheumatoid arthritis, which is a typical disease induced by Th17, to treat IgG or F6 antibody, , And CD4 + T cells were separated and the degree of Th17 differentiation was measured. As a result, Th17 differentiation was observed in a disease model treated with IgG as a control, whereas Th17 differentiation was significantly suppressed in a disease model treated with F6 antibody (FIG. 2) The model showed that rheumatoid arthritis improved significantly (Figure 3). Therefore, it was confirmed that the F6 antibody inhibited the differentiation of Th17 cells and had a therapeutic effect on autoimmune diseases caused by Th17.

Therefore, the pharmaceutical composition comprising the F6 antibody of the present invention as an active ingredient can be usefully used for prevention and treatment of autoimmune diseases.

In the present invention, the term "treatment or prevention" means any action that inhibits, alleviates or advantageously alters a clinical condition associated with an autoimmune disease by using a pharmaceutical composition containing the F6 antibody as an active ingredient. Preferably, a composition comprising an F6 antibody can protect tissue from the development or accelerated progression of autoimmune disease by Th17 cells by inhibiting the differentiation of Th17 cells.

In the present invention, the autoimmune disease can be used for all autoimmune diseases induced by Th17, and preferable examples include psoriasis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, autoimmune myocarditis, atopic dermatitis, contact Hypersensitivity, inflammatory bowel disease, and periodontal disease.

The pharmaceutical composition comprising the F6 antibody of the present invention may be formulated to further comprise a pharmaceutically acceptable carrier.

As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not significantly stimulate the organism and does not interfere with the biological activity and properties of the administered compound. The pharmaceutically acceptable carrier in the present invention may be a mixture of saline, sterilized water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more components of these components, If necessary, other conventional additives such as antioxidants, buffers and bacteriostats may be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulated into injectable solutions, pills, capsules, or tablets such as aqueous solutions, suspensions, emulsions and the like.

Also, preferably, the pharmaceutical composition of the present invention may further include a filler, an excipient, a disintegrant, a binder, a lubricant, and the like. The pharmaceutical composition of the present invention may also be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatine capsules, sterile injectable solutions, sterile powders.

In another aspect, the invention is directed to a method of treating an autoimmune disease comprising administering a pharmaceutical composition comprising an F6 antibody.

The term "administering" as used herein means introducing the pharmaceutical composition of the present invention to a patient by any appropriate method, and the administration route of the composition of the present invention may be administered orally or parenterally in various routes ≪ / RTI >

A method of treatment of the present invention comprises administering a pharmaceutically effective amount of an F6 antibody. It will be apparent to those skilled in the art that the appropriate total daily dose may be determined by the practitioner within the scope of sound medical judgment. Preferably, the dosage of the pharmaceutical composition may be in the range of about 10 mg to about 200 mg per kg, and may be administered in single or divided doses. For purposes of the present invention, however, the specific therapeutically effective amount for a particular patient will depend upon the nature and extent of the reaction to be achieved, the particular composition, including whether or not other agents are used, the age, weight, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used or concurrently used with the specific composition, and similar factors well known in the medical arts.

The pharmaceutical composition comprising the anti-VEGF antibody of the present invention inhibits the differentiation of Th17 cells, thereby protecting tissues from the development or accelerated progress of autoimmune diseases caused by Th17 cells, thereby being useful for prevention and treatment of autoimmune diseases .

FIG. 1 shows the results of comparing the VEGF binding capacity of the F6 antibody of the present invention with (a), the known anti-VEGF antibody avastin's VEGF binding ability (b), and the binding potency with the Kd value (c).
FIG. 2 is a graph showing the degree of differentiation of Th17 in the spleen of a Th17-related disease animal model. FIG. In FIG. 2 (A), WT is a normal group that did not induce disease, IgG was treated with IgG in the disease inducing group, F6 was treated with F6 antibody in the disease inducing group, and spleen was extracted from each animal FACS analysis results for one cell are shown. Fig. 2 (B) is a graph showing the ratio of the Th17 cell group on the basis of the FACS data.
FIG. 3 is a graph showing the therapeutic effect of the F6 antibody against an anti-Th17-related rheumatoid arthritis animal model, wherein normal is a normal group in which no disease is induced, IgG is a group treated with IgG, The swelling score of the foot when treated with antibody is shown. And & circ & indicates the time of administration twice.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.

Example  1. Preparation of F6 Antibody

The F6 antibody of the present invention was prepared by the method described in Korean Patent Laid-Open No. 10-2010-0059374, which is incorporated herein by reference in its entirety.

Example  2. SPR  ( 표면 plasmon resonance ) Binding analysis

The Kd value was measured using Proteon XPR36 Protein Interaction Array System (bioRad, CA, USA), an SPR technique, to measure the binding strength of avastin and the F6 antibody of the present invention to VEGF. F6, avastin, and BSA were fixed to a GLC gold chip according to the instructions. VEGF-his was flowed at a rate of 100 mL / min for 120 seconds at various concentrations specified in the figure. The binding strength was then calculated using Proteon Manager ^TM software (ver 2.1) and the Langmuir 1: 1 binding model was used for the calculation. The results are shown in FIG. 1, in which the response to VEGF flowed as an experiment to measure the binding strength of avastin to F6 was converted into a physical signal.

As shown in FIG. 1, the binding intensity was measured using a Langmuir 1: 1 binding model. As a result, it was confirmed that the VEGF binding intensity of F6 was higher than that of Avastin.

Example  3. Th17  Inhibitory effect on cell differentiation

To a 24 well plate was added 2 [mu] g / ml of anti-CD3 antibody (BD pharmingen 553058) and incubated overnight at 4 [deg.] C. Spleen was extracted from mice treated with IgG and F6 antibody of Example 1 in a disease model in which type II collagen was injected into 7-week-old DBA1 / J rats to induce rheumatoid arthritis, and MACS CD4 + CD4 + T cells were isolated using a T cell isolation kit (MACS 130-090-860). All anti-CD3 antibodies were removed from the 24-well plate that was prepared the day before and 5 × 10 ⁵ cells were added per well. IL-4 antibody (10 占 퐂 / ml, R & D system MAB404), anti-IL-4 antibody (10 占 퐂 / -6 (50 ng / ml, R & D system 406-ML) and TGF-beta (1 ng / ml, R & D system 240-B). After 5 days, ionomycin (500 ng / ml, Sigma-aldrich I0638), PMA (5 ng / Lt; / RTI > Mouse anti-mouse IL-17A (eBioscience, 11-7177) with PE-conjugated anti-mouse / human RoRy (t) (eBioscience 12-6988-80) and anti- mouse CD4 APC (eBioscience 17-0041) -81) were treated for 1 hour, and the degree of Th17 differentiation was confirmed by BD FACSCalibur ™ flow cytometry (BD science).

The results are shown in Fig. In Fig. 2 (A), the cell group that is positive for CD4 and expressing IL-17A is Th17. FIG. 2 (B) is a graph showing the ratio of the Th17 cell group based on the FACS data. These results indicate that the disease-inducing group (IgG) has a higher Th17 differentiation rate than the non-disease inducing group (WT). However, in the group treated with F6 antibody after inducing the disease, it was found that Th17 differentiation was remarkably inhibited and recovered similar to the normal level.

Example  4. Rheumatism  Therapeutic effect in arthritis animal model

An animal model of rheumatoid arthritis was constructed by using mouse monoclonal anti-type II collagen 5 clone antibody cocktail kit (chondrex 53010) in 7-week-old DBA1 / J rats as manual. Briefly, 6 mg of 5-clone cocktail was intraperitoneally administered and 25-50 μg of LPS was intraperitoneally administered after 3 days. After LPS administration, F6 was administered at a dose of 12.5 mg / kg twice at two days intervals, and IgG was administered intraperitoneally as a negative control.

The degree of paw swelling of each animal was measured and shown in Fig. The degree of swelling of the feet means that the disease is very serious when the total score of 20 points reaches 5 points for each leg. In the case of IgG treatment group, induction of swelling of the foot was found to be increased when the rats were treated with the IgG treatment group, but the swelling score of the F6 antibody treated group was lower than that of the normal group, Indicating that it has an improving effect of arthritis.

<110> CATHOLIC UNIVERSITY INDUSTRY ACADEMIC COOPERATION FOUNDATION          A & R therapeutics co., Ltd. <120> Composition for preventing and treating autoimmune diseases          comprising anti-VEGF antibody <130> DPP20114343KR <160> 10 <170> Kopatentin 1.71 <210> 1 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> a light chain variable region of F6 antibody <400> 1 Gln Leu Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln   1 5 10 15 Arg Val Thr Ile Ser Cys Thr Gly Ser Asn Ser Asn Ile Gly Ala Gly              20 25 30 His Asp Val His Trp Tyr Gln Gln Leu Pro Gly Ala Ala Pro Lys Val          35 40 45 Val Ile Tyr Gly Asn Thr Asn Arg Ala Ser Gly Val Pro Glu Arg Phe      50 55 60 Ser Gly Ser Lys Ser Ala Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu  65 70 75 80 Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Asn Ser                  85 90 95 Leu Ser Gly Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu             100 105 110 <210> 2 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> a light chain variable region of F6 antibody <400> 2 cagctcgtgc tgactcagcc gccctcagtc tctggggccc cagggcagag ggtcaccatc 60 tcctgcaccg gaagcaactc caacatcggg gcaggtcatg atgtccattg gtaccagcaa 120 cttccaggag cagcccccaa agtcgtcatc tatggtaaca ctaatcgggc ctctggggtt 180 cctgagcgat tctctggctc caagtctgcc acctcagcct ccctggccat cactgggctc 240 caggctgagg atgaggctga ttattactgc cagtcctatg acaacagcct gagtggttat 300 gtcttcggaa ctgggaccaa ggtcaccgtc cta 333 <210> 3 <211> 118 <212> PRT <213> Artificial Sequence <220> <223> a heavy chain variable region of F6 antibody <400> 3 Gln Val Thr Leu Arg Glu Ser Gly Pro Thr Met Val Lys Pro Thr Gln   1 5 10 15 Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Ser              20 25 30 Gly Val Ala Val Gly Trp Ile Arg Gln Pro Pro Gly Gln Ala Leu Glu          35 40 45 Trp Leu Ala Leu Ile Tyr Trp Asp Asn Asp Lys Arg Tyr Ser Ser Ser      50 55 60 Leu Lys Asn Arg Leu Thr Val Ala Lys Asp Thr Ser Lys Ser Gln Val  65 70 75 80 Val Leu Thr Met Thr Asn Met Asp Pro Met Asp Thr Ala Thr Tyr Tyr                  85 90 95 Cys Ala His Gly Asp Gly Trp Leu Phe Asp Phe Trp Gly Gln Gly Thr             100 105 110 Leu Val Thr Val Ser Ser         115 <210> 4 <211> 354 <212> DNA <213> Artificial Sequence <220> <223> a heavy chain variable region of F6 antibody <400> 4 caggtcacct tgagggagtc tggtcctacg atggtgaaac ccacacagac cctcacgctg 60 acctgcacct tctctgggtt ctcactcagc actagtggag tggctgtggg ctggatccgt 120 cagcccccgg gacaggccct ggagtggctt gcactcattt attgggataa tgataagcgc 180 tacagcccat ctctaaaaaa cagactcacc gtcgccaagg acacctccaa aagccaggtg 240 gtccttacca tgaccaacat ggaccctatg gacacagcca catattactg tgcacacggc 300 gatggctggt tatttgactt ctggggccag ggcaccctgg tcaccgtctc ctca 354 <210> 5 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> CDR1 of a heavy chain variable region <400> 5 Thr Ser Gly Val Ala Val Gly   1 5 <210> 6 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> CDR2 of a heavy chain variable region <400> 6 Leu Ile Tyr Trp Asp Asn Asp Lys Arg Tyr Ser Pro Ser Leu Lys Asn   1 5 10 15 <210> 7 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> CDR3 of a heavy chain variable region <400> 7 Gly Asp Gly Trp Leu Phe Asp Phe   1 5 <210> 8 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> CDR1 of a light chain variable region <400> 8 Thr Gly Ser Asn Ser Asn Ile Gly Ala Gly His Asp Val His   1 5 10 <210> 9 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> CDR2 of a light chain variable region <400> 9 Gly Asn Thr Asn Arg Ala Ser   1 5 <210> 10 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> CDR3 of a light chain variable region <400> 10 Gln Ser Tyr Asp Asn Ser Leu Ser Gly Tyr Val   1 5 10

Claims (5)

A heavy chain variable region comprising a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 5, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 6, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 7; And a light chain variable region comprising a light chain CDR1 having the amino acid sequence of SEQ ID NO: 8, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 9, and a light chain CDR3 having the amino acid sequence of SEQ ID NO:
For the prevention or treatment of autoimmune diseases induced by Th17 cells selected from the group consisting of asthma, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, autoimmune myocarditis, atopic dermatitis, contact hypersensitivity, inflammatory bowel disease and periodontal disease Composition.
The composition of claim 1, wherein the monoclonal antibody comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 3.
2. The composition of claim 1, wherein said monoclonal antibody specifically binds to VEGF.
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