Anti-tweakr antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2016237160-A1
Application number	US-201414898455-A
Country	US
Kind code	A1
Filing date	Jun 12, 2014
Priority date	Jun 14, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for the TWEAKR (TNFRSF12A, FN14). The antibodies, accordingly, can be used to treat tumors and other disorders and conditions associated with expression of the TWEAKR. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for us.

First claim

1 . An isolated anti-TWEAKR antibody or an antigen-binding fragment thereof, which specifically binds to the D at position 47 (D47) of TWEAKR as depicted in SEQ ID NO:169.

2 . The antibody or an antigen binding fragment thereof according to claim 1 wherein the antibody is an agonistic antibody.

3 . The antibody or an antigen binding fragment thereof according to claim 1 , which comprises:
a variable heavy chain comprising: (a) a heavy chain CDR1 encoded by an amino acid sequence comprising the formula PYPMX (SEQ ID NO: 171), wherein X is I or M; (b) a heavy chain CDR2 encoded by an amino acid sequence comprising the formula YISPSGGXTHYADSVKG (SEQ ID NO: 172), wherein X is S or K; and (c) a heavy chain CDR3 encoded by an amino acid sequence comprising the formula GGDTYFDYFDY (SEQ ID NO: 173); and a variable light chain comprising: (a) a light chain CDR1 encoded by an amino acid sequence comprising the formula RASQSISXYLN (SEQ ID NO: 174), wherein X is G or S; (b) a light chain CDR2 encoded by an amino acid sequence comprising the formula XASSLQS (SEQ ID NO: 175), wherein X is Q, A, or N; and (c) a light chain CDR3 encoded by an amino acid sequence comprising the formula QQSYXXPXIT (SEQ ID NO: 176), wherein X at position 5 is T or S, and X at position 6 is T or S, and X at position 8 is G, or F.

4 . The antibody or an antigen binding fragment thereof according to claim 1 comprising:
a. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 6, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 7, and the variable heavy chain CDR3 sequence as presented by SEQ ID NO: 8, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 3, the variable light chain CDR2 sequence presented by SEQ ID NO: 4, and the variable light chain CDR3 sequence presented by SEQ ID NO: 5, or

b. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 16, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 17, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:18, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 13, the variable light chain CDR2 sequence presented by SEQ ID NO: 14, and the variable light chain CDR3 sequence presented by SEQ ID NO:15, or

c. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 26, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 27, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:28, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 23, the variable light chain CDR2 sequence presented by SEQ ID NO: 24, and the variable light chain CDR3 sequence presented by SEQ ID NO:25, or

d. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 36, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 37, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:38, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 33, the variable light chain CDR2 sequence presented by SEQ ID NO: 34, and the variable light chain CDR3 sequence presented by SEQ ID NO:35, or

e. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 46, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 47, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:48, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 43, the variable light chain CDR2 sequence presented by SEQ ID NO: 44, and the variable light chain CDR3 sequence presented by SEQ ID NO:45, or

f. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 56, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 57, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:58, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 53, the variable light chain CDR2 sequence presented by SEQ ID NO: 54, and the variable light chain CDR3 sequence presented by SEQ ID NO:55, or

g. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 66, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 67, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:68, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 63, the variable light chain CDR2 sequence presented by SEQ ID NO: 64, and the variable light chain CDR3 sequence presented by SEQ ID NO:65, or

h. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 76, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 77, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:78, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 73, the variable light chain CDR2 sequence presented by SEQ ID NO: 74, and the variable light chain CDR3 sequence presented by SEQ ID NO:75, or

i. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 86, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 87, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:88, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 83, the variable light chain CDR2 sequence presented by SEQ ID NO: 84, and the variable light chain CDR3 sequence presented by SEQ ID NO:85, or

j. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 96, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 97, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:98, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 93, the variable light chain CDR2 sequence presented by SEQ ID NO: 94, and the variable light chain CDR3 sequence presented by SEQ ID NO:95, or

k. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 106, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 107, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:108, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 103, the variable light chain CDR2 sequence presented by SEQ ID NO: 104, and the variable light chain CDR3 sequence presented by SEQ ID NO:105 or

l. a variable heavy chain comprising the variable heavy chain CDR1 sequence as presented by SEQ ID NO: 116, the variable heavy chain CDR2 sequence as presented by SEQ ID NO: 117, the variable heavy chain CDR3 sequence as presented by SEQ ID NO:118, and
a variable light chain comprising the variable light chain CDR1 sequence presented by SEQ ID NO: 113, the variable light chain CDR2 sequence presented by SEQ ID NO: 114, and the variable light chain CDR3 sequence presented by SEQ ID NO:115.

5 . The antibody or antigen-binding fragment thereof according to claim 1 comprising:
a. a variable heavy chain sequence as presented by SEQ ID NO:10 and a variable light chain sequences as presented by SEQ ID NO:9, or
b. a variable heavy chain sequence as presented by SEQ ID NO:20 and a variable light chain sequences as presented by SEQ ID NO:19, or
c. a variable heavy chain sequence as presented by SEQ ID NO:30 and a variable light chain sequences as presented by SEQ ID NO:29, or
d. a variable heavy chain seq

Assignees

• Bayer Pharma AG

Inventors

• Votsmeier Christian
• Hammer Stefanie
• Gritzan Uwe
• Berndt Sandra
• Zubov Dmitry
• Linden Lars
• Christian Sven
• Harrenga Axel
• Birkenfeld Jörg
• Freiberg Christoph
• Golfier Sven
• Eicker Andrea
• Greven Simone
• Stelte-Ludwig Beatrix
• Raschke Marian

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title