Amgen Inc. et al. vs Bristol-Myers Squibb Company

Director Discretionary Decision: Deny

Patent Owner's Preliminary Response

Declaration of Peter P. Lee, M.D.

Curriculum Vitae of Peter P. Lee, M.D.

U.S. Food and Drug Administration, The Drug Development Process, Step 3: Clinical Research (Content current as of Jan. 4, 2018), available at https://www.fda.gov/patients/drug-development-process/step-3-clinical-research

Wang, D.D. et al. Fixed Dosing Versus Body Size–Based Dosing of Monoclonal Antibodies in Adult Clinical Trials, J Clin Pharmacol., 2009 Sep; 49(9):1012-24

NCT01024231, “Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma” (Last Update Posted Mar. 22, 2021), available at https://clinicaltrials.gov/study/NCT01024231

Press Release, Bristol-Myers Squibb, Bristol-Myers Squibb Completes Acquisition of Medarex, Inc. (Sept. 1, 2009), available at https://news.bms.com/news/details/2009/Bristol-Myers-Squibb-to-Acquire-Medarex/default.aspx

National Institutes of Health, National Cancer Institute, NCI Dictionary of Cancer Terms, Definition of “complete response” available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/complete-response (last visited July 9, 2025)

National Institutes of Health, National Cancer Institute, NCI Dictionary of Cancer Terms, Definition of “partial response” available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/partial-response (last visited July 9, 2025)

NCT00730639, “A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)” (Last Update Posted Dec. 3, 2021), available at https://clinicaltrials.gov/study/NCT00730639

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OPDIVO FDA Approval label and prescribing information, December 2014

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U.S. Patent No. 8,008,449

Patent Term Extension certificate for U.S. Patent No. 8,008,449

Notice of Final Determination Eligible for U.S. Patent No. 8,008,449

U.S. Patent No. 9,358,289

Bristol-Myers Squibb Company Form 10-K (Dec. 31, 2024)

Opdivo FDA Approval label and prescribing information, May 2025

Keytruda FDA Approval label and prescribing information, June 2025

Biosimilar-Related IPR Petitions, Biologicshq.com

Biosimilar-Related IPRs by Reference Product, Biologicshq.com

Patents Subject to Biosimilar-Related IPRs and Litigations, Biologicshq.com

Biosimilars Council White Paper, Breaking Through on Biosimilars, Delivering More-Affordable, Innovative Medicines to America's Patients,

Biosimilars in the United States 2023-2027, Iqvia.com

Biosimilars Forum Applauds the Trump Administration for Drug Pricing Executive Order, Biosimilarsforum.org

The U.S. Generic & Biosimilar Medicines Savings Report, September 2024

Petitioner's Opposition to Patent Owner's Discretionary Denial Brief

Press Release, Bristol-Myers Squibb, FDA Approves Yervoy™ (ipilimumab) for the Treatment of Patients with Newly Diagnosed or Previously-Treated Unresectable or Metastatic Melanoma, the Deadliest Form of Skin Cancer (Mar. 25, 2011)

Press Release, Bristol-Myers Squibb, Bristol-Myers Squibb Receives Accelerated Approval of Opdivo (nivolumab) from the U.S. Food and Drug Administration (Dec. 22, 2014)

YERVOY, FDA Approved label and prescribing information, Rev. 5/2025

OPDIVO, FDA Approved label and prescribing information, Rev. 5/2025

Amgen Pipeline

NCT05907122, “A Study to Evaluate Similarity of ABP 206 Compared With OPDIVO® (Nivolumab) in Subjects With Resected Melanoma” (Last Update Posted Nov. 27, 2024)

Press Release, Amgen, Amgen Reports First Quarter 2025 Financial Results (May 1, 2025)

Press Release, Amgen, Amgen Reports Fourth Quarter and Full Year 2024 Financial Results (Feb. 4, 2025)

NCT01024231, “Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma” (Last Update Posted Mar. 22, 2022)

U.S. Patent No. 8,008,449

U.S. Patent No. 8,779,105

U.S. Patent No. 9,084,776

U.S. Patent No. 9,358,289

U.S. Patent No. 9,387,247

U.S. Patent No. 9,492,539

U.S. Patent No. 9,492,540

U.S. Patent No. 10,441,655

Sharma, P., et al. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps, 11(11) Nat. Rev. Cancer at 805-812 (2011)

U.S. Patent No. 8,728,474

Brittain, B., Bristol Myers sues AstraZeneca over cancer-treatment patents, Reuters (Mar. 18, 2022)

Complaint, Bristol-Myers Squibb Co. and E.R. Squibb & Sons, L.L.C., v. AstraZeneca Pharmaceuticals LP and AstraZeneca UK LTD., Civil Action No. 1:22-cv-00346-UNA (D. Del. filed Mar. 17, 2022)

Amgen Biosimilars, available at https://www.amgen.com/science/biosimilars

PATENT OWNER’S REQUEST FOR DISCRETIONARY DENIAL

Notice: Notice filing date accorded

Notice: Mandatory Notice

Notice: Power of Attorney

U.S. Patent No. 9,856,320

Prosecution History of U.S. Patent No. 9,856,320

Declaration of Paul A. Antony, M.D.

Curriculum Vitae of Dr. Paul A. Antony

NCT01024231 Version 3, ClinicalTrials.gov ("NCT-231")

International Patent Publication No. WO 2006/121168 A1 ("Korman")

Wolchok et al., Lancet Oncol. 2010 Feb; 11(2):155–64.

Bristol Myers Squibb Press Release announcing Ipilimumab FDA Approval

Sznol et al., J Clin Oncology. 2010 May 20; 28(15).

Fife et al., Immunol Rev. 2008 Aug; 224:166– 182.

NCT00323882 Version 1, ClinicalTrials.gov

NCT00729950 Version 1, ClinicalTrials.gov

NCT00441337 Version 1, ClinicalTrials.gov

NCT00730639 Version 1, ClinicalTrials.gov

Parry et al., Mol Cell Biol. 2005 Nov; 25(21):9543-53.

Okazaki et al., Int Immunol. 2007 Jul; 19(7):813-24.

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European Patent Application No. 17189595.6, Amended Claims, 10/18/2018

Curriculum Vitae of Prescott Lassman

European Patent Application No. 17189595.6, Reply to Exam Div Commun

European Patent Application No. 17189595.6, Annex to the Communication

Wolchok et al., N Engl J Med. 2013 Jun 2; 369(2):122-33.

Declaration of Prescott Lassman

ClinicalTrials.gov, Glossary of Common Site Terms

Curran et al., Proc Natl Acad Sci USA. 2010 Mar 2; 107(9):4275–4280.

NCT01024231 Version 58, ClinicalTrials.gov

Humphrey et al., J Natl Cancer Inst. 2011 Aug 17; 103(16):1222–1226.

European Patent Application No. 17189595.6, Notice of Withdrawal

European Patent Application No. 22196038.8 Amended claims after EP SR

European Patent Application No. 22196038.8, Ltr accompanying amendments

Hodi et al., Proc Nat’l Acad Sci USA. 2003 Apr 15; 100(8):4712–4717.

Brahmer et al., J Clin Oncology. 2010 Jul 1; 28(19):3167–3175.

Declaration of Sylvia D. Hall-Ellis, Ph.D.

Wolchok et al., N Engl J Med. 2011 Jun 30; 346(26):2517-1526.

Tourneau et al., J Natl Cancer Inst. 2009 May 20; 101(10):708–720.

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Ascierto et al., Semin Oncol. 2010 Oct; 37(5):508-16.

Korman et al., J Immunology. 2007 Apr; 178(1_Supplement):S82 (abstract).

ClinicalTrials.gov, Clinical Trial Reporting Requirements

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ClinicalTrials.gov, How to Edit Your Study Record

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Affidavit of Nathaniel E. Frank-White (Internet Archive)(“Frank White Aff")

Wolchok et al., Supplementary Appendix. N Engl J Med. 2013 Jul 11; 369(2)

Power of Attorney

Petition for Inter Partes Review