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Generated: September 22, 2017

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Title:Combination therapy using anti-EGFR and anti-HER2 antibodies
Abstract: The invention relates to the combined use of anti-EGFR antibodies and anti-Her2 antibodies for the treatment of cancer, especially suitable for cancer expressing high levels of the EGFR type and low levels of HER2. The invention refers in particular monoclonal antibody \"trastuzumab\" (HERCEPTIN.RTM.) directed against the HER2 receptors the efficacy of which can be significantly increased in vivo when combined with monoclonal antibody \"matuzumab\" (hmAB 425, EMD 72000) directed against EGF receptors. The combination treatment is suitable for patients suffering from cancer having said receptor profile, preferably pancreatic cancer.
Inventor(s): Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR)
Assignee: L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR)
Application Number:14/536,854
Patent Claims:1. A method for treating pancreatic cancer in an individual, wherein said pancreatic cancer in said individual overexpresses EGFR and does not or not significantly expresses HER2, the method comprising administering to the individual an anti-HER2 antibody and an anti-EGFR antibody, said anti-HER2 antibody and said anti-EGFR antibody being both part of the same bispecific antibody, wherein said anti-HER2 antibody is murine, chimeric or humanized mAb 4D5 (trastuzumab) or pertuzumab and said anti-EGFR antibody is murine, chimeric or humanized mAb 425 (matuzumab); chimeric mAb 225 (cetuximab); or panitumumab.

2. The method of claim 1, wherein HER2 is not expressed.

3. The method of claim 1, wherein said antibody is fused at its C-terminus to a biologically effective peptide, polypeptide or protein, optionally via a linker peptide, thus forming an immunoconjugate.

4. The method of claim 3, wherein said immunoconjugate is an immunocytokine.

5. The method of claim 1, wherein said pancreatic cancer in said individual has been determined to overexpress EGFR and to not or not significantly express HER2.

6. The method according to claim 1, wherein EGFR are expressed with a higher rate and/or amount than for normal non-tumor cells.

7. A method for improving the efficacy of the treatment of pancreatic cancer with an anti-HER2 antibody, wherein said pancreatic cancer in said individual overexpresses EGFR and does not or not significantly expresses HER2; the method comprising administering to an individual an anti-HER2 antibody and an anti-EGFR antibody, said anti-HER2 antibody and said anti-EGFR antibody being both part of the same bispecific antibody, wherein said anti-HER2 antibody is murine, chimeric or humanized mAb 4D5 (trastuzumab) or pertuzumab and said anti-EGFR antibody is murine, chimeric or humanized mAb 425 (matuzumab); chimeric mAb 225 (cetuximab); or panitumumab.

8. The method of claim 7, wherein HER2 is not expressed.

9. The method of claim 1, wherein said antibody is immunologically effective fragment.

10. The method of claim 1, wherein additionally a cytotoxic agent is administered to the individual.

11. The method of claim 10, wherein the cytotoxic agent is a chemotherapeutic agent.

12. The method of claim 11, wherein the chemotherapeutic agent is selected from the group consisting of cisplatin, doxorubicin, gemcitabine, docetaxel, paclitaxel, bleomycin and irinotecan.

13. The method of claim 10, wherein the cytotoxic agent is a VEGF receptor inhibitor, a small molecule tyrosine kinase inhibitor, an anti-angiogenic agent, or a cytokine.

14. The method of claim 7, wherein said cancer in said individual has been determined to overexpress EGFR and to not or not significantly express HER2.

15. The method according to claim 7, wherein EGFR are expressed with a higher rate and/or amount than for normal non-tumor cells.

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Foriegn Application Priority Data
Foreign Country Foreign Patent Number Foreign Patent Date
06000107Jan 4, 2006

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Inventors Patent Expiration Status Orphan Source
Genentech
HERCEPTIN
trastuzumab
VIAL; INTRAVENOUS1037920011998-09-25► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXOrphansearch
Imclone
ERBITUX
cetuximab
VIAL; INTRAVENOUS1250840012004-06-18► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXOrphansearch
Amgen
VECTIBIX
panitumumab
INJECTABLE; IV (INFUSION)1251470012006-09-27► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXsearch
Amgen
VECTIBIX
panitumumab
INJECTABLE; IV (INFUSION)1251470022006-09-27► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXsearch
Amgen
VECTIBIX
panitumumab
INJECTABLE; IV (INFUSION)1251470032006-09-27► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXsearch
Genentech
PERJETA
pertuzumab
VIAL; SINGLE-USE1254090012012-06-08► Subscribe L\'Institut National de la Sante et de la Recherche Medicale (Paris, FR) Gillies; Stephen D. (Carlisle, MA), Azria; David (Mauguio, FR), Larbouret; Christel (Montpellier, FR), Pelegrin; Andre (Montpellier, FR) ► SubscribeRXsearch
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International Patent Family for Patent: ► Subscribe

Country Document Number Publication Date
Argentina059127Mar 12, 2008
Australia2006332212Jul 12, 2007
Australia2006332212Mar 28, 2013
Australia2006332212May 30, 2013
BrazilPI0620888Nov 29, 2011
Canada2636074Jul 12, 2007
China101365486Feb 11, 2009
China101365486Oct 31, 2012
Eurasian Patent Organization015173Jun 30, 2011
Eurasian Patent Organization200870141Feb 27, 2009
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Moodys
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Chinese Patent Office

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