KR20130031136A - Composition for preventing and treating autoimmune diseases comprising anti-vegf antibody - Google Patents

Abstract

The present invention relates to the use of preventing and treating autoimmune diseases comprising a specific anti-VEGF antibody designated F6, and more particularly, the present invention is directed to Th17 cells by inhibiting the differentiation of Th17 cells. The present invention relates to the use of preventing and treating induced autoimmune diseases. 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

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

The present invention relates to the use of preventing and treating autoimmune diseases comprising a specific anti-VEGF antibody designated F6, and more particularly, the present invention is directed to Th17 cells by inhibiting the differentiation of Th17 cells. The present invention relates to the use of preventing and treating induced autoimmune diseases. Therefore, the present invention relates to a pharmaceutical composition and a method for preventing and treating autoimmune diseases comprising the anti-VEGF antibody.

The human immune system protects the body from foreign antigens that invade the body, but does not attack its own tissues because of its self tolerance. However, when the immune system's self-tolerance is destroyed and the protein normally expressed by one's genes is recognized by the immune cell as the target of attack, the antibody is made or the T-cell reaction causes the normal tissue to be destroyed. It is called autoimmune disease.

In the mid-1980s, Mosmann et al. Suggested that helper T lymphocytes (Th) could be divided into two cell groups, Th1 and Th2, according to cytokine secretion (Mosmann TR, et al., J Immunol., 136: 2348-2357, 1986). Since Th1 cells secrete IFN-γ and activate macrophages to induce cellular immune responses, Th2 cells secrete IL-4, IL-5, etc. and are involved in humoral immune responses. In addition, it is known that inflammatory autoimmune disease is caused by excessive progression of Th1 due to imbalance between Th1 and Th2 cells. However, reports have been reported that mice deficient in IFN-γ or IFN receptors cause autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (19), which raised questions about the Th1 / Th2 paradigm (Infante-Duarte C, et al., J.). Immunol., 165: 6107-6115, 2000), studies of IL-12 and IL-23 have shown that Th17 cells induced by IL-23 are more important than Th1 cells in causing autoimmune diseases (Murphy KM, et al., Nat Rev Immunol 2 (12): 933-44, 2002; Cua DJ, et al., 421 (6924): 744-8, 2003; Langrish CL, et al., J Exp Med 201 ( 2): 233-40, 2005)

Th17 cells are so named because the T cell population induced by IL-23 secretes IL-17 cytokines, and has been found to be independent of Th1 or Th2. Recently, transcription factors of Th17 cells called RORγt have been revealed, and the signaling system and transcription process of Th17 cells have been identified. In addition, Th17 cells, unlike Th1, Th2 and Treg (regulatory T cell) cells, have been found to be involved in the forefront of the inflammatory response seen in autoimmune diseases, thereby maximizing the signal of the inflammatory response and accelerating disease progression. Accordingly, the development of therapeutic agents for autoimmune diseases that target the inhibition of Th17 cell activity has been greatly highlighted.

Specifically, Th17 is psoriasis (Wilson, NJ, et al., Nat Immunol, 8 (9): 950-957, 2007; Arican, O., et al., Mediators Inflamm, 2005 (5): 273-279, 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), Rheumatoid arthritis (Lee, HS, et al., 13 (9-10): 455-460, 2007; Remmers, EF, et al., N Engl J Med, 357 (10): 977-986, 2007; Mathur , AN, et al., J Immunol, 178 (8): 4901-4907, 2007), systemic sclerosis (Zhou, L., et al., 8 (9): 967-974, 2007; Distler, JH, et. al., 52 (3): 856-864, 2005), systemic lupus erythematosus (Wong, CK, et al., Lupus, 9 (8): 589-593, 2000; Kang, HK, et al., J 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 (Molet) , S., et al., J Allergy Clin Immunol, 108 (3): 430-438, 2001; Barczyk, A., et al., Respir Med, 97 (6): 726-733, 2003; Bullens, D. M., et al., Respir Res, 7: 135, 2006; Wong, CK, et al., Clin Exp Immunol, 125 (2): 177-183, 2001), atopic dermatitis and contact hypersensitivity (van Beelen, AJ, et al., Curr Opin Allergy Clin Immunol, 7 (5) : 374-381, 2007; Nakae, S., et al., 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 , R., et al., World J Gastroenterol, 13 (39): 5238-5244, 2007; Wada, Y., et al., Blood, 109 (3): 1156-1164, 2007) and periodontal disease (Oda) , T., et al., Oral Microbiol Immunol, 18 (1): 30-36, 2003; Johnson, RB, et al., J Periodontol, 75 (1): 37-43. 2004; Takahashi, K., et al., J Clin Periodontol, 32 (4): 369-374, 2005; Vernal, R., et al., J Clin Periodontol, 32 (4): 383-389, 2005). It has been reported as a therapeutic target for the disease.

Currently, immunosuppressive agents that block signal transduction pathways in T cells are most commonly used as therapeutic agents for autoimmune diseases, but these immunosuppressive agents are toxic, infected, lymphoma, diabetes, tremor, headache, diarrhea, high blood pressure, nausea, There is a problem that side effects such as renal failure occur. Therefore, there is a need for the development of a new immune disease treatment agent that is inexpensive and has excellent therapeutic effect.

On the other hand, the team used 14 recombinant human antibodies that specifically bind to VEGF using recombinant VEGF from a phage library made from human-derived scFv library cells in a previous study (Domestic Patent Publication No. 10-2010-0059374). Screened and structured. In addition, it was confirmed that the anti-VEGF antibodies bind to VEGF in humans and mice with high affinity and inhibit capillary-like tube formation induced by VEGF in vascular endothelial cells, thereby inducing cancer or angiogenesis by VEGF overexpression. It has been provided as a treatment for vascular diseases.

Accordingly, the present inventors further studied the physiological function of the antibody named F6 in the anti-VEGF antibody, and the F6 antibody inhibits the differentiation of Th17 cells, thereby having an excellent effect on the treatment of Th17-related autoimmune diseases. It will be newly identified to complete the present invention.

An object of the present invention is 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 autoimmune disease comprising administering a pharmaceutical composition comprising the antibody.

In one embodiment, the present invention is to provide a pharmaceutical composition for preventing and treating autoimmune diseases comprising an anti-VEGF antibody named F6.

Preferably, the antibody comprises a heavy chain variable region comprising a heavy chain CDR1 having an amino acid sequence of SEQ ID NO: 5, a heavy chain CDR2 having an amino acid sequence of SEQ ID NO: 6, and a heavy chain CDR3 having an amino acid sequence of SEQ ID NO: 7; And a light chain variable region comprising a light chain CDR1 having an amino acid sequence of SEQ ID NO: 8, a light chain CDR2 having an amino acid sequence of SEQ ID NO: 9, and a light chain CDR3 having an amino acid sequence of SEQ ID NO: 10.

Preferably, the antibody is a monoclonal antibody comprising a light chain variable region having an amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region having an 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 is referred to by genetic engineering such as chimeric antibodies, humanized antibodies, human antibodies, and heterologous antibodies (eg, bispecific antibodies). Include the form produced. In addition, the term "antibody" in the present invention includes not only whole antibody forms but also functional fragments of antibody molecules. In general, an antibody has a structure having two full length light chains and two full length heavy chains, and each light chain is linked by a heavy chain and a disulfide bond. In the present invention, the antibody includes a functional fragment of an antibody molecule having an antigen binding function, and the fragment includes Fab, Fab ', F (ab') 2, Fd, Fv, dAb, scFv, bivalent. Or bispecific molecules, diabodies, triabodies, tetrabodies, and the like.

As used herein, the term "variable region" refers to a region that performs a function of specifically binding to an antigen among antibodies, and in the variable region, CDR1, CDR2 and CDR3, which are complementarity determining regions, are present. A framework region (FR) portion exists between the CDRs to support the CDR rings.

The antibody of the present invention is characterized in that it specifically binds to VEGF. In a specific embodiment of the present invention, the binding strength was measured using a Langmuir 1: 1 binding model, it was confirmed that the binding strength of F6 to VEGF is superior to the known anti-VEGF antibody Avastin (FIG. 1). ).

The antibody of the present invention can be prepared by a general method known in the art, for example, by a genetic 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 technology of the invention, the presence of Th17, a cell belonging to secondary T lymphocytes (Th) and independent of Th1 or Th2, has been reported, and Th17 cells induced by IL-23 are more autologous than Th1 cells. It has been found to be more important for causing immune diseases. Th17 cells are involved in the forefront of the inflammatory response seen in autoimmune diseases, thereby maximizing the signal of the inflammatory response, accelerating disease progression, and developing therapeutic agents for autoimmune diseases by targeting the inhibition of Th17 cell activity.

The inventors have identified for the first time that F6 antibodies can be used as therapeutic agents for autoimmune diseases associated with Th17 cells by inhibiting the differentiation of Th17 cells. In a specific embodiment of the present invention, by injecting collagen type 2 into 7-week-old DBA1 / J mice, an animal model of rheumatoid arthritis, a representative disease induced by Th17, was constructed and treated with IgG or F6 antibody, respectively, and spleen was extracted. , CD4 + T cells were isolated to determine the degree of Th17 differentiation. As a result, it was found that Th17 differentiation was remarkably suppressed in the disease model treated with F6 antibody while high Th17 differentiation rate was shown in the disease model treated with IgG as a control (FIG. 2). In the model, it was confirmed that rheumatoid arthritis improved markedly (FIG. 3). Therefore, it was confirmed that the F6 antibody has a therapeutic effect on Th17-induced autoimmune diseases by inhibiting Th17 cell differentiation.

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

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

In the present invention, autoimmune diseases can be used for all autoimmune diseases induced by Th17, and as a preferred example, psoriasis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, autoimmune myocarditis, atopic dermatitis, contact Hypersensitivity, inflammatory bowel disease and periodontal disease, but is not limited thereto.

Pharmaceutical compositions comprising the F6 antibodies of the invention may be formulated to further include 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 used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, If desired, other conventional additives such as antioxidants, buffers and bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations, 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 fillers, excipients, disintegrants, binders and lubricants. The pharmaceutical compositions of the invention may also be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable drugs, sterile powders.

In another aspect, the present invention relates to a method for treating autoimmune disease comprising administering a pharmaceutical composition comprising an F6 antibody.

As used herein, the term "administration" means introducing a pharmaceutical composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be various oral or parenteral routes as long as it can reach the desired tissue. It can be administered through.

The treatment method of the present invention comprises administering a pharmaceutically effective amount of the 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 used in the range of about 10 mg to about 200 mg per kg, and may be administered one time or divided into several times. However, for the purposes of the present invention, the specific therapeutically effective amount for a particular patient is determined by the specific composition, including the type and extent of the reaction to be achieved, whether or not other agents are used in some cases, the age, weight, general health of the patient, It is desirable to apply differently depending on various factors and similar factors well known in the medicinal art, including sex and diet, time of administration, route of administration and rate of composition, duration of treatment, drugs used with or concurrent with the specific composition.

The pharmaceutical composition comprising the anti-VEGF antibody of the present invention may be useful for the prevention and treatment of autoimmune diseases by inhibiting the differentiation of Th17 cells, thereby protecting the tissues from the development or accelerated progression of autoimmune diseases by Th17 cells. Can be.

Figure 1 shows the results of comparing the VEGF binding capacity of the F6 antibody of the present invention (a), the VEGF binding capacity (b) of Avastin, a known anti-VEGF antibody (b), and each binding capacity by the Kd value (c).
Figure 2 is a diagram showing the degree of differentiation of Th17 in the spleen of Th17-related disease animal model. In FIG. 2 (A), WT is a normal group that does not induce disease, IgG is a disease-induced group treated with IgG, and F6 is treated with an F6 antibody in a disease-induced group, and spleens are extracted from each animal. The results of FACS analysis 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.
3 is a diagram showing the therapeutic effect of the F6 antibody on Th17-related rheumatoid arthritis animal model, where normal is a disease-free group, IgG is a disease-induced group, and F6 is a disease-induced group. The swelling score of the foot is shown when the antibody is treated. ▲ indicates the time of administration in two doses.

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 Publication No. 10-2010-0059374, which is incorporated by reference in its entirety.

Example  2. SPR  ( 표면 plasmon resonance Binding analysis

Kd values were measured using SPR technology ProteOn XPR36 Protein Interaction Array System (bioRad, CA, USA) to measure the binding strength of Avastin and VEGF of the F6 antibody of the present invention. 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 indicated in the figure. Since binding strength was calculated using Proteon Manager ^TM software (ver 2.1), the Langmuir 1: 1 binding model was used in the calculation. Experiments to measure the bond strength of Avastin and F6, how to respond to the VEGF flowed to the physics signal was calculated by converting the results are shown in FIG.

As shown in FIG. 1, binding strength was measured using the Langmuir 1: 1 binding model, and it was confirmed that VEGF binding strength of F6 was superior to Avastin.

Example  3. Th17  Cell differentiation inhibitory effect

2 μg / ml of anti-CD3 antibody (BD pharmingen 553058) was added to a 24 well plate and incubated at 4 ° C. overnight. Spleen was extracted from mice treated with IgG and the F6 antibody prepared in Example 1 in a disease model induced by rheumatoid arthritis by injecting collagen type 2 into 7-week-old DBA1 / J mice, which were then treated with MACS CD4 +. CD4 + T cells were isolated using T cell separation kit (MACS 130-090-860). All anti-CD3 antibodies were removed from the 24 well plates prepared the day before and 5 × 10 ⁵ cells were added per well. Anti-CD28 antibody (5 μg / ml, BD pharmigen 553295), anti-IFNγ antibody (10 μg / ml, R & D system MAB485), anti-IL-4 antibody (10 μg / ml, R & D system MAB404), IL -6 (50 ng / ml, R & D system 406-ML), TGF-β (1 ng / ml, R & D system 240-B) were added. Five days later, ionomycin (500 ng / ml, sigma-aldrich I0638), PMA (5 ng / ml, sigma P8139), golgi plug (1 ug / ml, BD bioscience 555029) were added, and 37 ° C. for 4 hours. Incubated at. PE-coupled anti-mouse / human RoRγ (t) with anti-mouse CD4 APC (eBioscience 17-0041) (eBioscience 12-6988-80) and FITC-coupled anti-mouse IL-17A (eBioscience, 11-7177 The cells differentiated with -81) were treated for 1 hour and then the degree of Th17 differentiation was confirmed by BD FACSCalibur ™ flow cytometry (BD science).

The results are shown in FIG. In FIG. 2 (A), a cell group positive for CD4 and expressing IL-17A is Th17. The graph which computed the ratio of Th17 cell group based on this FACS data is shown to FIG. 2 (B). Looking at this, it can be seen that the disease-induced group (IgG) has a higher Th17 differentiation rate than the disease-induced group (WT). However, in the group treated with F6 antibody after induction of disease, Th17 differentiation was remarkably suppressed and recovered similarly to normal levels.

Example  4. Rheumatism  Therapeutic Effects in Arthritis Animal Models

Rheumatoid arthritis animal model was constructed in 7-week-old DBA1 / J mice using a mouse monoclonal anti-type II collagen 5 clone antibody cocktail kit (chondrex 53010) as a manual. Briefly, 6 mg of 5-clone cocktail was administered intraperitoneally, and after 3 days, 25-50 μg of LPS was intraperitoneally administered. F6 and IgG were administered intraperitoneally, respectively, at a concentration of 12.5 mg / kg twice daily at two days after LPS administration.

The degree of swelling of the paw was measured for each animal and is shown in FIG. 3. The degree of swelling of the foot means that the disease is very serious when the total reaches 20 points out of 5 points for each leg. Compared to the normal group, the IgG treated group increased the swelling of the foot when inducing rheumatoid arthritis, but the swelling score was lowered in the F6 antibody treated group. Has an improvement in 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 Pro 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 an amino acid sequence of SEQ ID NO: 5, a heavy chain CDR2 having an amino acid sequence of SEQ ID NO: 6, and a heavy chain CDR3 having an amino acid sequence of SEQ ID NO: 7; And a monoclonal antibody comprising a light chain variable region comprising a light chain CDR1 having an amino acid sequence of SEQ ID NO: 8, a light chain CDR2 having an amino acid sequence of SEQ ID NO: 9, and a light chain CDR3 having an amino acid sequence of SEQ ID NO: 10 Prophylactic and therapeutic compositions.
The composition of claim 1, wherein the monoclonal antibody comprises a light chain variable region having an amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region having an amino acid sequence of SEQ ID NO: 3.
The composition of claim 1, wherein the monoclonal antibody specifically binds VEGF.
The composition of claim 1, wherein the autoimmune disease is a disease induced by Th17 cells.
The composition of claim 1, wherein the autoimmune disease is 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. .

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