PD-L1-specific antibodies and methods of using the same
AssigneeCheckpoint Therapeutics, Inc.
InventorsJonathan Belk, Nathan J. Sharkey, Leonid Gorelik
Life of this patent
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Abstract
The present disclosure relates generally to antibodies and functional binding fragments thereof that bind to programmed death-ligand 1 (PD-L1). In particular, the disclosed antibodies and fragments bind to human PD-L1 and comprise novel complementary determining regions (CDRs) also disclosed herein. Finally, the present disclosure relates to administering the disclosed antibodies and fragments to subjects with cancer, thereby treating or slowing the progression or proliferation of the cancer.
Claims31
An antibody or a fragment thereof that binds to human programmed death-ligand 1 (PD-L1), wherein the antibody or fragment thereof comprises:
- a heavy chain comprising:
- CDRH1 comprising amino acids 1-3 and 7-9 of SEQ ID NO:
- 1, wherein amino acids 4-6 are not SSY;
- CDRH2 comprising amino acids 9-17 of SEQ ID NO:
- 8;
- and CDRH3 comprising SEQ ID NO:
- 15;
- and
- a light chain comprising CDRL1 comprising SEQ ID NO:
- 20;
- CDRL2 comprising SEQ ID NO:
- 21;
- and CDRL3 comprising SEQ ID NO:
- 22, SEQ ID NO:
- 75, or SEQ ID NO:
- 76.
An antibody or a fragment thereof that binds to human programmed death-ligand 1 (PD-L1), wherein the antibody or fragment thereof comprises a heavy chain comprising SEQ ID NO:
- 35.
A method of inhibiting cancer cell proliferation in a subject, comprising administering an antibody or fragment that binds human PD-L1 with a KD of at least 8.30×10−9;
- a CDRH2 comprising SEQ ID NO:
- 9, 10, 11, 12, 13, or 14;
- and CDRH3 comprising SEQ ID NO:
- 15 to a subject with cancer.
A method of inhibiting tumor cell proliferation in a subject, comprising administering an antibody or fragment thereof that binds human PD-L1 with a KD of at least 2.50×10−8 and CDRH3 comprising amino acids 6-13 of SEQ ID NO:
- 18 to a subject with cancer.
A method of treatment, comprising administering to a subject with cancer an anti-PD-L1 antibody comprising:
- (i) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 2, a CDRH2 comprising SEQ ID NO:
- 9, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (ii) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 3, a CDRH2 comprising SEQ ID NO:
- 10, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (iii) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 4, a CDRH2 comprising SEQ ID NO:
- 11, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (iv) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 5, a CDRH2 comprising SEQ ID NO:
- 12, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (v) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 6, a CDRH2 comprising SEQ ID NO:
- 13, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (vi) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 7, a CDRH2 comprising SEQ ID NO:
- 14, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 22;
- (vii) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 2, a CDRH2 comprising SEQ ID NO:
- 9, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 75;
- or
- (viii) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 2, a CDRH2 comprising SEQ ID NO:
- 9, and a CDRH3 comprising SEQ ID NO:
- 15;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 20, a CDRL2 comprising SEQ ID NO:
- 21, and a CDRL3 comprising SEQ ID NO:
- 76.
A method of treatment, comprising administering to a subject with cancer an anti-PD-L1 antibody comprising:
- (i) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 16, a CDRH2 comprising SEQ ID NO:
- 17, and a CDRH3 comprising SEQ ID NO:
- 18;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 23, a CDRL2 comprising SEQ ID NO:
- 24, and a CDRL3 comprising SEQ ID NO:
- 25;
- or
- (ii) a heavy chain comprising a CDRH1 comprising SEQ ID NO:
- 16, a CDRH2 comprising SEQ ID NO:
- 17, and a CDRH3 comprising SEQ ID NO:
- 19;
- and a light chain comprising a CDRL1 comprising SEQ ID NO:
- 23, a CDRL2 comprising SEQ ID NO:
- 24, and a CDRL3 comprising SEQ ID NO:
- 25.
Dependencies are inferred from the claim text.