Anti-psma antibodies, conjugates, and methods of use
AssigneeEisai R&D Management Co., Ltd.
InventorsJared SPIDEL, Dae-Shik KIM, Kenzo ARAI, Keiji FURUUCHI, Xin CHENG, Xingfeng BAO, Yoshinobu YAMANE, Yosuke KABURAGI, Kuan-Chun HUANG, Earl F. ALBONE
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Abstract
Antibodies, antigen-binding fragments, and conjugates (e.g., antibody-drug conjugates) thereof that bind PSMA, as well as STING agonist linker-drug conjugates and preparation thereof, are disclosed. The disclosure further relates to methods and compositions for use in the treatment of, e.g., cancer by administering the compositions provided herein.
Claims180
A humanized anti-prostate-specific membrane antigen (PSMA) antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment binds specifically to human PSMA, and wherein the antibody or antigen-binding fragment comprises
- (i) three HCDRs comprising amino acid sequences of SEQ ID NO:
- 21 (HCDR1), SEQ ID NO:
- 22 (HCDR2), and SEQ ID NO:
- 27 (HCDR3);
- and three LCDRs comprising SEQ ID NO:
- 32 (LCDR1), SEQ ID NO:
- 35 (LCDR2), and SEQ ID NO:
- 37 (LCDR3), as defined by the Kabat numbering system;
- or
- (ii) three HCDRs comprising amino acid sequences of SEQ ID NO:
- 21 (HCDR1), SEQ ID NO:
- 22 (HCDR2), and SEQ ID NO:
- 27 (HCDR3);
- and three LCDRs comprising SEQ ID NO:
- 33 (LCDR1), SEQ ID NO:
- 36 (LCDR2), and SEQ ID NO:
- 37 (LCDR3), as defined by the Kabat numbering system;
- or
- (iii) three HCDRs comprising amino acid sequences of SEQ ID NO:
- 28 (HCDR1), SEQ ID NO:
- 29 (HCDR2), and SEQ ID NO:
- 30 (HCDR3);
- and three LCDRs comprising SEQ ID NO:
- 38 (LCDR1), SEQ ID NO:
- 39 (LCDR2), and SEQ ID NO:
- 37 (LCDR3), as defined by the IMGT numbering system.
A linker-payload conjugate comprising L-D, wherein L is a linker that covalently attaches to D, wherein D comprises a compound according to one of the following Formulae:
- an isomer thereof, a deuterated derivative of the compound or isomer;
- or a salt of the compound, isomer, or deuterated derivative;
- wherein, independently for each occurrence,
- each of Pa and Pb, when not racemic, is independently selected from (R)-stereochemistry and (S)-stereochemistry;
- each of Qa and Qb is independently selected from NH and O;
- each of Va and Vb is independently selected from F and OH;
- W is selected from H and NH2;
- each of Xa and Xb is independently selected from OH and SH;
- each of Ya and Yb is independently selected from O and S;
- each Za and Zb is independently selected from CH2, O, and NH;
- and
- means that the bond is selected from a single bond (), a double bond () of (E)- or (Z)-configuration, or a triple bond ();
- provided that at least one of Za and Zb is NH or at least one of Xa and Xb is SH.
Dependencies are inferred from the claim text.