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Thursday, August 10, 2017 9:46:45 AM
U.S. Patent #9,492,518
”Tumor Immunity - Disclosed herein are materials and methods for treating cancer. In particular, compositions for stimulating tumor immunity through modulation of MFG-E8 are provided.”
Inventors: Dranoff, Glenn (Lexington, MA), Jinushi, Masahisa (Tokyo)
Assignee: Dana-Farber Cancer Institute (Boston)
Filed: 10-4-2007, PCT Pub. Date: 4-10-2008, Approved: 11-15-2016
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=9,492,518.PN.&OS=PN/9,492,518&RS=PN/9,492,518
= = = = =CONTINUATION:
U.S. Patent Appl. #20170224793: Filed: 9/26/2016, Pub: 8/10/2017
http://www.freepatentsonline.com/y2017/0224793.html
“This application is a continuation of U.S. patent application #12/444,047, filed Mar. 4, 2010 and issued as U.S. Pat. #9,492,518 on Nov. 15, 2016, which is the U.S. National Phase of Intl. Patent Appl. #PCT/US07/80446, filed Oct. 4, 2007, which claims priority to U.S. Provisional Patent Appl.# 60/828,177, filed Oct. 4, 2006. The contents of each application listed above are incorporated herein by reference in their entireties.”
SUMMARY:
Methods and compositions for cancer therapy are provided. In particular, the methods and compositions described herein stimulate immune-mediated tumor destruction. The present invention is based, in part, on the discovery that conditions that result in the downregulation of MFG-E8 can potentiate GM-CSF stimulated tumor destruction to provoke a clinical anti-tumor response.
. . .
In another embodiment, the MFG-E8 inhibitor is selected from the group consisting of an anti-MFG-E8 antibody, an anti-phosphatidylserine antibody, an MFG-E8 polypeptide that lacks the ability to bind integrins; and an MFG-E8 polypeptide that lacks the ability to bind phosphatidylserine. The antibody can be a monoclonal antibody, a polyclonal antibody, an Fab fragment, a chimeric antibody, a humanized antibody or a single chain antibody. Regardless of the precise molecular form of the antibody, the antibody is a pharmaceutically pure antibody.
ANTIBODIES:
An MFG-E8 inhibitor can be an antibody. In one embodiment, the antibody can be an anti-MFG-E8 antibody. In another embodiment, the antibody can be an anti-PS antibody. Anti-PS antibodies and ligands for binding PS are described in U.S. Pat. Nos. 6,406,693, 6,818,213, 6,312,694, and 6,783,760 and in Beck et al. 2006 Int J Cancer 118:2639-43. Anti-PS antibodies e.g., Bavituximab (Peregrine Pharmaceuticals), are also described on the NCI trials database at http//canger.gov/clinical trials. In another embodiment, the antibody can be an antibody that specifically recognizes and blocks the activity of a molecule that functions in the uptake of PS. Examples of PS-uptake targets include Del-1 (see for example, without limitation, NP_005702, GI:31317224), Gas6 (see for example, without limitation, NP_000811, GI:4557617), Mer (see for example, without limitation, NP_006334, GI:66932918) and members of the Tyro family (see for example, without limitation, NP_006284, GI:27597078.) As used herein, useful antibodies can include: monoclonal and polyclonal antibodies, single chain antibodies, chimeric antibodies, bifunctional/bispecific antibodies, humanized antibodies, human antibodies, and complementary determining region (CDR)-grafted antibodies, that are specific for the target protein or fragments thereof, and also include antibody fragments, including Fab, Fab', F(ab')2, scFv, Fv, camelbodies, or microantibodies.
MFG-E8: https://en.wikipedia.org/wiki/MFGE8
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