Combination therapy with antibody-drug conjugates

A technology for coupling compounds and antibodies, applied in the field of combined therapy with antibody-drug conjugates, can solve the unmet medical needs of HL patients and other problems

Active Publication Date: 2011-02-09
SEATTLE GENETICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, the medical ne...

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  • Combination therapy with antibody-drug conjugates
  • Combination therapy with antibody-drug conjugates
  • Combination therapy with antibody-drug conjugates

Examples

Experimental program
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Effect test

Embodiment 1

[0480] Example 1 : Antibody-drug conjugate cAC10-vcMMAE (cAC10-MC-vc-PAB-MMAE) in combination with chemotherapy regimens for the treatment of HL

[0481]The effect of combined cAC10-vcMMAE therapy with gemcitabine or ABVD or other chemotherapy regimens was studied in the L540cy tumor model (Francisco et al., Blood 2003; 102:1458-146). To determine the maximum tolerated dose (MTD) of ABVD and gemcitabine, body weights of SCID mice treated with increasing amounts of drug were assessed daily. MTD was assessed by ≥20% weight loss or other signs of morbidity throughout the treatment period and subsequent 2-week recovery period. The time to tumor quadrupling or tripling was chosen as the time to endpoint (TTE), and nonlinear regression analysis was performed on individual tumor growth data sets for each experimental animal in exponential growth phase to determine this endpoint. Time to tumor quadrupling was calculated based on tumor volume at the start of treatment. The TTE valu...

Embodiment 2

[0505] Example 2: Antibody-drug conjugate cAC10-mcMMAF combined with gemcitabine for the treatment of HL

[0506] The effect of cAC10-mcMMAF treatment in combination with gemcitabine was studied in the same manner as the experiments used for cAC10-vcMMAE. Choose 1 mg / kg, q4dx3 regimen for cAC10-mcMMAF. On Day 51 of the trial, 9 / 10 sustained responses were observed in the combination arm compared with 0 / 10 in the cAC10-mcMMAF monotherapy arm and 0 / 10 in the gemcitabine single arm arm. 10 sustained responses. The experiment is on day 51 and has not yet been completed.

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Abstract

Methods for the treatment of Hodgkin's lymphoma comprising administering both a chemotherapeutic regimen and an antibody-drug conjugate compound to a subject in need thereof are provided.

Description

[0001] continue to apply [0002] This application claims U.S. Provisional Patent Application No. 60 / 979,594, filed December 10, 2007; U.S. Provisional Patent Application No. 60 / 027,668, filed November 2, 2008; and U.S. Provisional Patent Application, filed March 28, 2008 Priority of No. 61,040,641; the entire contents of which are incorporated herein by reference. technical field [0003] The present invention relates to methods of treatment of Hodgkin's lymphoma and the like, said methods comprising administering a chemotherapy regimen and an antibody-drug conjugate compound to a subject in need thereof. Background technique [0004] Hodgkin's lymphoma (HL) is a neoplasm of the lymphoid tissue defined histopathologically by the presence of malignant Hodgkin-Rie-Sch (HRS) cells. A characteristic surface antigen expressed on HRS cells is CD30. In the United States and Canada, an estimated 8,000 new cases of HL are diagnosed each year. Advances in the use of combined chemo...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K31/7064
CPCA61K31/7064A61K47/48561A61K47/48415C07K16/2878A61K39/39533A61K47/6811A61K47/6849A61P35/00A61P43/00A61K2300/00A61K39/395
Inventor E·奥夫拉佐格鲁E·西弗斯H·格伯
Owner SEATTLE GENETICS INC
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