Host cell comprising nucleic acids encoding bispecific antibodies binding to beta-klotho and fibroblast growth factor receptor 1 and antibody production
AssigneeGenentech, Inc.
InventorsYongmei Chen, James Ernst, Hok Seon Kim, Junichiro Sonoda, Christoph Spiess, Scott Stawicki, Yan Wu
Life of this patent
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Abstract
The presently disclosed subject matter provides antibodies that bind KLB and FGFR1, and methods of using the same. In certain embodiments, an antibody of the present disclosure includes a bispecific antibody that binds to an epitope present on FGFR1 and binds to an epitope present on KLB.
Claims21
A host cell comprising a nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
- (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 136;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 137;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 138;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 139;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 140;
- and
- (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 141.
A host cell comprising a nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
- (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 15;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 31;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 47;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 62;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 78;
- and
- (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 93.
A host cell comprising a nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
- a first arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 136;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 137;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 138;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 139;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 140;
- and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 141;
- and
- (ii) a second arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 15;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 31;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 47;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 62;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 78;
- and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 93.
A method of producing an antibody comprising culturing a host cell so that the antibody is produced, wherein the host cell comprises a nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
- (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 136;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 137;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 138;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 139;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 140;
- and
- (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 141.
A method of producing an antibody comprising culturing a host cell so that the antibody is produced, wherein the host cell comprises a nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
- (i) a first arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 136;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 137;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 138;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 139;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 140;
- and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 141;
- and
- (ii) a second arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 15;
- (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 31;
- (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 47;
- (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 62;
- (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 78;
- and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO:
- 93.
Dependencies are inferred from the claim text.