Anti-PTK7 antibody-drug conjugates
Inventors
Damelin, Marc Isaac • Sapra, Puja • BANKOVICH, Alexander John • Dylla, Scott J.
Assignees
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Publication Number
US-9777070-B2
Publication Date
2017-10-03
Expiration Date
Abstract
The present invention provides anti-PTK7 antibody-drug conjugates and methods for preparing and using the same.
Core Innovation
The invention relates to an antibody-drug conjugate of the formula Ab-(L-D) that targets human protein tyrosine kinase 7 (PTK7). The Ab binds PTK7 and includes heavy chain and light chain amino acid sequence sets forth as SEQ ID NO: 37 and SEQ ID NO: 47, or embodiments including SEQ ID NO: 13 and SEQ ID NO: 23. The conjugate further includes a linker-drug moiety L-D in which L is a linker and D is an auristatin.
Linker embodiments include maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc) and maleimidocaproyl (mc). The auristatin payload is provided as auristatin 0101 and auristatin 8261, including auristatin moieties having specified formulas. The antibody-drug conjugate is characterized by drug-to-antibody ratio (DAR) constraints including a DAR of 1 to 8.
The disclosed ADCs are associated with PTK7-overexpressing cancers and PTK7-associated disorders. The therapeutic use includes administering a composition containing the antibody-drug conjugate to a subject in need thereof, with disorder and tumor-type selections including solid tumors and hematologic malignancies.
Claims Coverage
The independent claims cover three core antibody-drug conjugate structures defined by Ab-(L-D) with PTK7-binding antibodies specified by heavy/light sequence identifiers and auristatin linker-drug moieties. Across the independent claims, the coverage includes specific PTK7-binding sequence combinations, auristatin payloads, linker-drug construction, and a DAR range of 1 to 8 in at least one independent claim set.
PTK7-binding antibody-drug conjugate of Ab-(L-D)
An antibody-drug conjugate of the formula Ab-(L-D), wherein Ab binds human PTK7 comprising a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 37 and a light chain comprising an amino acid sequence set forth as SEQ ID NO: 47, and wherein L-D is a linker-drug moiety having L as a linker and D as an auristatin.
PTK7-binding vc-linked auristatin 0101 conjugate with DAR 1 to 8
An antibody-drug conjugate of the formula Ab-(L-D), wherein Ab binds human PTK7 comprising a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 37 and a light chain comprising an amino acid sequence set forth as SEQ ID NO: 47, and wherein L-D is a linker-drug moiety with L as maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc) and D as auristatin 0101, and wherein the antibody-drug conjugate has a drug-to-antibody ratio (DAR) of 1 to 8.
PTK7-binding antibody-drug conjugate of Ab-(L-D) with alternate PTK7-binding chains
An antibody-drug conjugate of the formula Ab-(L-D), wherein Ab binds human PTK7 comprising a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 13 and a light chain comprising an amino acid sequence set forth as SEQ ID NO: 23, and wherein L-D is a linker-drug moiety having L as a linker and D as an auristatin.
Across the independent claims, the central coverage is the Ab-(L-D) ADC format where Ab binds PTK7 using specified heavy/light amino acid sequence identifiers, the drug component D is an auristatin, and embodiments specify a particular linker (vc) and auristatin 0101 with DAR of 1 to 8.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating PTK7-associated disorders by administering to a subject a therapeutically effective amount of a composition containing the antibody-drug conjugate.
Treatment of solid tumors selected from enumerated cancer types, including breast cancer, ovarian cancer, colorectal cancer, esophageal cancer, gastric cancer, melanoma, sarcoma, kidney cancer, pancreatic cancer, prostate cancer, liver cancer, and lung cancer.
Treatment of leukemia limited to adult myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).
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