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Patent Application

App. No. 13/501,430

USE OF IL-17 RECEPTOR A ANTIGEN BINDING PROTEINS

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Patent No.: US None
App. No.: 13/501,430

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Abstract

The present invention relates to IL-17 Receptor A (IL-17RA or IL-17R) antigen binding proteins, such as antibodies, polynucleotide sequences encoding said antigen binding proteins, and compositions and methods for treating diseases, such as various forms of cancer.

Claims (139)

1 . A method of treating cancer in a patient in need thereof, comprising administering to said patient an effective amount of a composition comprising an antibody that specifically binds human IL-17 Receptor A and inhibits the binding of IL-17A, wherein said antibody is selected from the group consisting of:

a. a light chain variable domain sequence that is at least 80% identical to a light chain variable domain sequence of AM L 1-26 (SEQ ID NOs:27-53, respectively);

b. a heavy chain variable domain sequence that is at least 80% identical to a heavy chain variable domain sequence of AM H 1-26 (SEQ ID NOs:1-26, respectively); or

c. the light chain variable domain of (a) and the heavy chain variable domain of (b); and

B. a light chain CDR1, CDR2, CDR3 and a heavy chain CDR1, CDR2, CDR3 that differs by no more than a total of three amino acid additions, substitutions, and/or deletions in each CDR from the following sequences:

a. a light chain CDR1 (SEQ ID NO:185), CDR2 (SEQ ID NO:186), CDR3 (SEQ ID NO:187) and a heavy chain CDR1 (SEQ ID NO:107), CDR2 (SEQ ID NO:108), CDR3 (SEQ ID NO:109) of antibody AM-1;

b. a light chain CDR1 (SEQ ID NO:188), CDR2 (SEQ ID NO:189), CDR3 (SEQ ID NO:190) and a heavy chain CDR1 (SEQ ID NO:110), CDR2 (SEQ ID NO:111), CDR3 (SEQ ID NO:112) of antibody AM-2;

c. a light chain CDR1 (SEQ ID NO:191), CDR2 (SEQ ID NO:192), CDR3 (SEQ ID NO:193) and a heavy chain CDR1 (SEQ ID NO:113), CDR2 (SEQ ID NO:114), CDR3 (SEQ ID NO:115) of antibody AM-3;

d. a light chain CDR1 (SEQ ID NO:194), CDR2 (SEQ ID NO:195), CDR3 (SEQ ID NO:196) and a heavy chain CDR1 (SEQ ID NO:116), CDR2 (SEQ ID NO:117), CDR3 (SEQ ID NO:118) of antibody AM-4;

e. a light chain CDR1 (SEQ ID NO:197), CDR2 (SEQ ID NO:198), CDR3 (SEQ ID NO:199) and a heavy chain CDR1 (SEQ ID NO:119), CDR2 (SEQ ID NO:120), CDR3 (SEQ ID NO:121) of antibody AM-5;

f. a light chain CDR1 (SEQ ID NO:200), CDR2 (SEQ ID NO:201), CDR3 (SEQ ID NO:202) and a heavy chain CDR1 (SEQ ID NO:122), CDR2 (SEQ ID NO:123), CDR3 (SEQ ID NO:124) of antibody AM-6;

g. a light chain CDR1 (SEQ ID NO:203), CDR2 (SEQ ID NO:204), CDR3 (SEQ ID NO:205) and a heavy chain CDR1 (SEQ ID NO:125), CDR2 (SEQ ID NO:126), CDR3 (SEQ ID NO:127) of antibody AM-7;

h. a light chain CDR1 (SEQ ID NO:206), CDR2 (SEQ ID NO:207), CDR3 (SEQ ID NO:208) and a heavy chain CDR1 (SEQ ID NO:128), CDR2 (SEQ ID NO:129), CDR3 (SEQ ID NO:130) of antibody AM-8;

i. a light chain CDR1 (SEQ ID NO:209), CDR2 (SEQ ID NO:210), CDR3 (SEQ ID NO:211) and a heavy chain CDR1 (SEQ ID NO:131), CDR2 (SEQ ID NO:132), CDR3 (SEQ ID NO:133) of antibody AM-9;

j. a light chain CDR1 (SEQ ID NO:212), CDR2 (SEQ ID NO:213), CDR3 (SEQ ID NO:214) and a heavy chain CDR1 (SEQ ID NO:134), CDR2 (SEQ ID NO:135), CDR3 (SEQ ID NO:136) of antibody AM-10;

k. a light chain CDR1 (SEQ ID NO:215), CDR2 (SEQ ID NO:216), CDR3 (SEQ ID NO:217) and a heavy chain CDR1 (SEQ ID NO:137), CDR2 (SEQ ID NO:138), CDR3 (SEQ ID NO:139) of antibody AM-11;

l. a light chain CDR1 (SEQ ID NO:218), CDR2 (SEQ ID NO:219), CDR3 (SEQ ID NO:220) and a heavy chain CDR1 (SEQ ID NO:140), CDR2 (SEQ ID NO:141), CDR3 (SEQ ID NO:142) of antibody AM-12;

m. a light chain CDR1 (SEQ ID NO:221), CDR2 (SEQ ID NO:222), CDR3 (SEQ ID NO:223) and a heavy chain CDR1 (SEQ ID NO:143), CDR2 (SEQ ID NO:144), CDR3 (SEQ ID NO:145) of antibody AM-13;

n. a light chain CDR1 (SEQ ID NO:224), CDR2 (SEQ ID NO:225), CDR3 (SEQ ID NO:226) and a heavy chain CDR1 (SEQ ID NO:146), CDR2 (SEQ ID NO:147), CDR3 (SEQ ID NO:148) of antibody AM-14;

o. a light chain CDR1 (SEQ ID NO:227), CDR2 (SEQ ID NO:228), CDR3 (SEQ ID NO:229) and a heavy chain CDR1 (SEQ ID NO:149), CDR2 (SEQ ID NO:150), CDR3 (SEQ ID NO:151) of antibody AM-15;

p. a light chain CDR1 (SEQ ID NO:230), CDR2 (SEQ ID NO:231), CDR3 (SEQ ID NO:232) and a heavy chain CDR1 (SEQ ID NO:152), CDR2 (SEQ ID NO:153), CDR3 (SEQ ID NO:154) of antibody AM-16;

q. a light chain CDR1 (SEQ ID NO:233), CDR2 (SEQ ID NO:234), CDR3 (SEQ ID NO:235) and a heavy chain CDR1 (SEQ ID NO:155), CDR2 (SEQ ID NO:156), CDR3 (SEQ ID NO:157) of antibody AM-17;

r. a light chain CDR1 (SEQ ID NO:236), CDR2 (SEQ ID NO:237), CDR3 (SEQ ID NO:238) and a heavy chain CDR1 (SEQ ID NO:158), CDR2 (SEQ ID NO:159), CDR3 (SEQ ID NO:160) of antibody AM-18;

s. a light chain CDR1 (SEQ ID NO:239), CDR2 (SEQ ID NO:240), CDR3 (SEQ ID NO:241) and a heavy chain CDR1 (SEQ ID NO:161), CDR2 (SEQ ID NO:162), CDR3 (SEQ ID NO:163) of antibody AM-19;

t. a light chain CDR1 (SEQ ID NO:242), CDR2 (SEQ ID NO:243), CDR3 (SEQ ID NO:244) and a heavy chain CDR1 (SEQ ID NO:164), CDR2 (SEQ ID NO:165), CDR3 (SEQ ID NO:166) of antibody AM-20;

u. a light chain CDR1 (SEQ ID NO:245), CDR2 (SEQ ID NO:246), CDR3 (SEQ ID NO:247) and a heavy chain CDR1 (SEQ ID NO:167), CDR2 (SEQ ID NO:168), CDR3 (SEQ ID NO:169) of antibody AM-21;

v. a light chain CDR1 (SEQ ID NO:248), CDR2 (SEQ ID NO:249), CDR3 (SEQ ID NO:250) and a heavy chain CDR1 (SEQ ID NO:170), CDR2 (SEQ ID NO:171), CDR3 (SEQ ID NO:172) of antibody AM-22;

w. a light chain CDR1 (SEQ ID NO:251), CDR2 (SEQ ID NO:252), CDR3 (SEQ ID NO:253) and a heavy chain CDR1 (SEQ ID NO:173), CDR2 (SEQ ID NO:174), CDR3 (SEQ ID NO:175) of antibody AM-23;

x. a light chain CDR1 (SEQ ID NO:254), CDR2 (SEQ ID NO:255), CDR3 (SEQ ID NO:256) and a heavy chain CDR1 (SEQ ID NO:173), CDR2 (SEQ ID NO:174), CDR3 (SEQ ID NO:175) of antibody AM-23;

y. a light chain CDR1 (SEQ ID NO:257), CDR2 (SEQ ID NO:258), CDR3 (SEQ ID NO:259) and a heavy chain CDR1 (SEQ ID NO:176), CDR2 (SEQ ID NO:177), CDR3 (SEQ ID NO:178) of antibody AM-24;

z. a light chain CDR1 (SEQ ID NO:260), CDR2 (SEQ ID NO:261), CDR3 (SEQ ID NO:262) and a heavy chain CDR1 (SEQ ID NO:179), CDR2 (SEQ ID NO:180), CDR3 (SEQ ID NO:181) of antibody AM-25; or

z.2. a light chain CDR1 (SEQ ID NO:263), CDR2 (SEQ ID NO:264), CDR3 (SEQ ID NO:265) and a heavy chain CDR1 (SEQ ID NO:182), CDR2 (SEQ ID NO:183), CDR3 (SEQ ID NO:184) of antibody AM-26;

wherein said polypeptide specifically binds IL-17 receptor A.

2 . The method of claim 1 , wherein said antibody comprises:

a. a heavy chain CDR1 comprising an amino acid sequence selected from the group consisting of:

i. X 1 YGIS, wherein X 1 is selected from the group consisting of R, S and G;

b. a heavy chain CDR2 comprising an amino acid sequence selected from the group consisting of:

i. WISX 1 YX 2 GNTX 3 YAQX 4 X 5 QG, wherein X 1 is selected from the group consisting of A, X 2 is selected from the group consisting of N, S and K, X 3 is selected from the group consisting of N and K, X 4 is selected from the group consisting of K and N, and X 5 is selected from the group consisting of L and F;

c. a heavy chain CDR3 comprising an amino acid sequence selected from the group consisting of:

i. X 1 QLX 2 X 3 DY, wherein X 1 is selected from the group consisting of R and K, X 2 is selected from the group consisting of Y, V, and A, and X 3 is selected from the group consisting of F and L;

ii. X 1 QLX 2 FDY, wherein X 1 is selected from the group consisting of R and K, and X 2 is selected from the group consisting of Y and V;

d. a light chain CDR1 comprising an amino acid sequence selected from the group consisting of:

i. RASQSX 1 X 2 X 3 X 4 LA, wherein X 1 is selected from the group consisting of V and I, X 2 is selected from the group consisting of I and S, X 3 is selected from the group consisting of S and T, X 4 is selected from the group consisting of N and S, and X 5 is selected from the group consisting of A and N, and

ii. RASQSX 1 SSNLA, wherein X 1 is selected from the group consisting of V and I;

e. a light chain CDR2 comprising an amino acid sequence selected from the group consisting of:

i. X 1 X 2 STRAX 3 , wherein X 1 is selected from the group consisting of G and D, X 2 is selected from the group consisting of A and T, and X 3 is selected from the group consisting of T and A, and

ii. X 1 ASTRAX 2 , wherein X 1 is selected from the group consisting of G and D, and X 2 is selected from the group consisting of A and T; and

f. a light chain CDR3 comprising an amino acid sequence selected from the group consisting of:

i. QQYDX 1 WPLT, wherein X 1 is selected from the group consisting of N, T, and I; wherein said antibody specifically binds IL-17 receptor A.

3 . The method of claim 2 , wherein said antibody comprises:

a. a heavy chain CDR1 amino acid sequence comprising X 1 YGIS, wherein X 1 is selected from the group consisting of R, S and G;

b. a heavy chain CDR2 amino acid sequence comprising WISX 1 YX 2 GNTX 3 YAQX 4 X 5 QG, wherein X 1 is selected from the group consisting of A, X 2 is selected from the group consisting of N, S and K, X 3 is selected from the group consisting of N and K, X 4 is selected from the group consisting of K and N, and X 5 is selected from the group consisting of L and F;

c. a heavy chain CDR3 amino acid sequence comprising X 1 QLX 2 FDY, wherein X 1 is selected from the group consisting of R and K, and X 2 is selected from the group consisting of Y and V;

d. a light chain CDR1 amino acid sequence comprising RASQSX 1 SSNLA, wherein X 1 is selected from the group consisting of V and I;

e. a light chain CDR2 amino acid sequence comprising X 1 ASTRAX 2 , wherein X 1 is selected from the group consisting of G and D, and X 2 is selected from the group consisting of A and T; and

f. a light chain CDR3 amino acid sequence comprising QQYDX 1 WPLT, wherein X 1 is selected from the group consisting of N, T, and I; wherein said antibody specifically binds IL-17 receptor A.

4 . The method of claim 1 , wherein said antibody comprises:

a. a light chain variable domain and a heavy chain variable domain of AM L 1/AM H 1 (SEQ ID NO:27/SEQ ID NO:1);

b. a light chain variable domain and a heavy chain variable domain of AM L 2/AM H 2 (SEQ ID NO:28/SEQ ID NO:2);

c. a light chain variable domain and a heavy chain variable domain of AM L 3/AM H 3 (SEQ ID NO:29/SEQ ID NO:3);

d. a light chain variable domain and a heavy chain variable domain of AM L 4/AM H 4 (SEQ ID NO: 30/SEQ ID NO:4);

e. a light chain variable domain and a heavy chain variable domain of AM L 5/AM H 5 (SEQ ID NO:31/SEQ ID NO:5);

f. a light chain variable domain and a heavy chain variable domain of AM L 6/AM H 6 (SEQ ID NO: 32/SEQ ID NO:6)

g. a light chain variable domain and a heavy chain variable domain of AM L 7/AM H 7 (SEQ ID NO:33/SEQ ID NO:7);

h. a light chain variable domain and a heavy chain variable domain of AM L 8/AM H 8 (SEQ ID NO: 34/SEQ ID NO:8);

i. a light chain variable domain and a heavy chain variable domain of AM L 9/AM H 9 (SEQ ID NO: 35/SEQ ID NO:9);

j. a light chain variable domain and a heavy chain variable domain of AM L 10/AM H 10 (SEQ ID NO:36/SEQ ID NO:10);

k. a light chain variable domain and a heavy chain variable domain of AM L 11/AM H 11 (SEQ ID NO:37/SEQ ID NO:11);

l. a light chain variable domain and a heavy chain variable domain of AM L 12/AM H 12 (SEQ ID NO:38/SEQ ID NO:12);

m. a light chain variable domain and a heavy chain variable domain of AM L 13/AM H 13 (SEQ ID NO:39/SEQ ID NO:13);

n. a light chain variable domain and a heavy chain variable domain of AM L 14/AM H 14 (SEQ ID NO:40/SEQ ID NO:14);

o. a light chain variable domain and a heavy chain variable domain of AM L 15/AM H 15 (SEQ ID NO:41/SEQ ID NO:15);

p. a light chain variable domain and a heavy chain variable domain of AM L 16/AM H 16 (SEQ ID NO:42/SEQ ID NO:16);

q. a light chain variable domain and a heavy chain variable domain of AM L 17/AM H 17 (SEQ ID NO:43/SEQ ID NO:17);

r. a light chain variable domain and a heavy chain variable domain of AM L 18/AM H 18 (SEQ ID NO:44/SEQ ID NO:18);

s. a light chain variable domain and a heavy chain variable domain of AM L 19/AM H 19 (SEQ ID NO:45/SEQ ID NO:19);

t. a light chain variable domain and a heavy chain variable domain of AM L 20/AM H 20 (SEQ ID NO:46/SEQ ID NO:20);

u. a light chain variable domain and a heavy chain variable domain of AM L 21/AM H 21 (SEQ ID NO:47/SEQ ID NO:21);

v. a light chain variable domain and a heavy chain variable domain of AM L 22/AM H 22 (SEQ ID NO:48/SEQ ID NO:22);

w. a light chain variable domain and a heavy chain variable domain of AM L 23/AM H 23 (SEQ ID NO: 49 or SEQ ID NO:50/SEQ ID NO:23);

x. a light chain variable domain and a heavy chain variable domain of AM L 24/AM H 24 (SEQ ID NO:51/SEQ ID NO:24);

y. a light chain variable domain and a heavy chain variable domain of AM L 25/AM H 25 (SEQ ID NO:52/SEQ ID NO:25); and

z. a light chain variable domain and a heavy chain variable domain of AM L 26/AM H 26 (SEQ ID NO:53/SEQ ID NO:26);

wherein said polypeptide specifically binds IL-17 receptor A.

5 . The method of claim 1 , wherein said antibody comprises: