Merck Sharp & Dohme LLC vs Halozyme, Inc. et al.

Authorized Response to Director Review Request

Patent Owner's Notice of Park Deposition

Patent Owner's Request for Director Review

Patent Owner's Objections to Evidence

Email, Subject_PGR2025-00009 Director Review Request

Petitioner's Objections to Evidence

Notice of Joint Stipulation to Modify Due Dates

Patent Owner's Updated Mandatory Notices

DECISION Granting Institution of Post-Grant Review 35 U.S.C. § 324

SCHEDULING ORDER

Petitioner's Updated Mandatory Notices

Patent Owner's Updated Power of Attorney

Patent Owner's Updated Mandatory Notices

Director Discretionary Decision: Refer

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

News Release, "Halozyme Raises 2025 Financial Guidance Ranges and Reports Strong First Quarter 2025 Results."

News Release, "Merck Breaks Ground on New $1 Billion Biologics Center of Excellence in Wilmington, Delaware."

Halozyme Therapeutics, Inc. Q1 2025 Earnings Call Transcript (May 6, 2025)

Patent Owner's Sur-Reply to Petitioner's Reply to Patent Owner's Preliminary Response

Patent Owner's Updated Power of Attorney

Patent Owner's Updated Mandatory Notices

Reply in Support of Petition for Post Grant Review

Patent Owner's Updated Mandatory Notices

Petitioner's Updates to Mandatory Notices

EX2046 - 2023 Pharma 50

EX2047 - Merck Financial Results

EX2048 - Products List - Merck.com

EX2050 - Merck Market Cap Nasdaq

EX2051 - Halozyme Market Cap Nasdaq

EX2052 - Halozyme News Revenue

EX2053 - Halozyme - Commercial Products

EX2054 - Halozyme - About Us

EX2055 - Triggs-Raine Declaration ISO Patent Owner Discretionary Denial Brief

EX2056 - PGR2025-00042 Petition

EX2057 - PGR2025-00042 EX1003 - Hecht Declaration

EX2058 - District Court Complaint

EX2059 - Alteogen announces amendment to license agreement with MSD

Patent Owner Discretionary Denial Brief

Patent Owner's Updated Mandatory Notices

Petitioner's Updates to Mandatory Notices

Patent Owner's Preliminary Response

EX2002 - Triggs-Raine CV

EX2003 - Disclaimer

EX2004 - Fierce Pharma

EX2005 - LinkedIn Profiles

EX2006 - Sequence Listing

EX2007 - Gifre 2017

EX2008 - Recombinant Drugs - Smithsonian Institution

EX2009 - Naz 2011

EX2010 - Primakoff 1988

EX2011 - Guinea Pig - Merriam-Webster 2010

EX2012 - Nature 2012

EX2013 - Lin 1993

EX2015 - USP7872107 File History (Part 1 of 3)

EX2015 - USP7872107 File History (Part 2 of 3)

EX2015 - USP7872107 File History (Part 3 of 3)

EX2016 - Pils 2005

EX2018 - Duterme 2009

EX2019 - Atmuri 2008

EX2020 - Hemming 2008

EX2021 - Miller 2008

EX2022 - Kaneiwa 2010

EX2023 - PGR2025-00004 Petition

EX2024 - PGR2025-00006 Petition

EX2025 - PGR2025-00003 Petition

EX2026 - PGR2025-00017 Petition

EX2027 - PGR2025-00030 Petition

EX2028 - PGR2025-00024 Petition

EX2029 - PGR2025-00004 EX1003 - Hecht Declaration

EX2030 - PGR2025-00006 EX1003 - Hecht Declaration

EX2031 - PGR2025-00003 EX1003 - Hecht Declaration

EX2032 - PGR2025-00017 EX1003 - Hecht Declaration

EX2033 - PGR2025-00030 EX1003 - Hecht Declaration

EX2034 - PGR2025-00024 EX1003 - Hecht Declaration

EX2035 - Lokeshwar 2002

EX2036 - PGR2025-00033 EX1003 - Hecht Declaration

EX2037 - PGR2025-00033 Petition

EX2038 - PGR2025-00039 EX1003 - Hecht Declaration

EX2039 - PGR2025-00039 Petition

EX2040 - Wilson 2002

EX2041 - Doig 2008

EX2042 - Cochran 2001

EX2043 - elMasry 1994

EX2001 - Triggs-Raine Declaration

Patent Owner's Updated Mandatory Notices

Order: Granting Petitioner's Motions for Pro Hac Vice Admission of Leif E. Peterson, II - 37 CFR 42.10

Petitioner's Motion for Pro Hac Vice Admission of Leif E. Peterson, II

Declaration of Leif E. Peterson

Patent Owner's Updated Mandatory Notices

Patent Owner's Updated Mandatory Notices

Patent Owner's Updated Mandatory Notices

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Patent Owner's Updated Mandatory Notices

Patent Owner's Power of Attorney

Patent Owner's Mandatory Notices

Notice: NOTICE OF FILING DATE ACCORDED TO PETITION AND TIME FOR FILING PATENT OWNER PRELIMINARY RESPONSE

U.S. Patent No. 12,123,035

File History of U.S. Patent No. 12,123,035 Part 1

File History of U.S. Patent No. 12,123,035 Part 2

U.S. Patent No. 7,767,429

Chao, Structure of Human Hyaluronidase-1 (2007)

WO/2010/077297, published July 8, 2010

Stern, The Hyaluronidases: Their Genomics, Structures, & Mechanisms (2006)

Jedzrejas, Structures of Vertebrate Hyaluronidases (2005)

Zhang, Hyaluronidase Activity of Human Hyal1 (2009)

Arming, In vitro Mutagenesis of PH-20 Hyaluronidase from Human Sperm (1997)

Bordoli, Protein Structure Homology Modeling Using SWISSMODEL (2008)

Frost, Recombinant Human Hyaluronidase (rHuPH20) (2007)

Brandon & Tooze, Introduction to Protein Structure (1999) Part 1

Brandon & Tooze, Introduction to Protein Structure (1999) Part 2

Table Associating ’035 Patent to Corresponding ’731 Application

Steipe, Consensus-Based Engineering of Protein Stability (2004)

Green, Computer Graphics, Homology Modeling, and Bioinformatics (2010)

Chica, Semi-rational Approaches to Engineering Enzyme Activity (2005)

Hardy, Assessment of Contraceptive Vaccines Based on Recombinant Mouse Sper

Pomering, Restricted Entry of IgG (2002)

Baba, Mouse Sperm Lacking Cell Surface Hyaluronidase PH-20 (2002)

Primakoff, Reversible Contraceptive Effect of PH-20 Immunization (1997)

Tung, Mechanism of Infertility in Male Guinea Pigs Immunized with Sperm

Rosengren, Recombinant Human PH20 (2018)

U.S. Patent No. 9,447,401

U.S. Patent Application No. 13/694,731

Gmachl, The Human Sperm Protein PH-20 Has Hyaluronidase Activity (1993)

Sills, "Retraction," Science, 319:569 (2008)

Yue, Loss of Protein Structure Stability as a Major Causative Factor (2005)

Wang & Moult, SNPs, Protein Structure, and Disease (2001)

Marković-Housley, Crystal Structure of Hyaluronidase (2000)

"Negative Results," Nature: Editorials, 453:258 (2008)

Lins, Analysis of Accessible Surface of Residues in Proteins (2003)

Hayden, Chemistry: Designer Debacle (2008)

Benkert, Toward the Estimation of the Absolute Quality (2010)

Schwede, SWISS-MODEL: An Automated Protein Homology-Modeling Server (2003)

Alberts, Molecular Biology of the Cell, Chapter 3 (2007)

He, NMR Structures of Two Designed Proteins with High Sequence Identity

Alexander, A Minimal Sequence Code for Switching Protein Structure (2009)

Ruan, Design & Characterization of a Protein Fold Switching Network (2023)

Sievers, Fast, Scalable Generation of High-Quality Protein (2011)

Mihel, PSAIA – Protein Structure and Interaction Analyzer (2008)

Redline Comparison of the ’731 and ’035 Specifications

Beasley & Hecht, Protein Design: The Choice of de Novo Sequences (1997)

Xiong, Periodicity of Polar and Nonpolar Amino Acids (1995)

Hayden, Key Protein-Design Papers Challenged (2009)

KEGG, DRUG: Hyaluronidase (human recombinant)

Pace & Scholtz, A Helix Propensity Scale (1998)

U.S. Patent Application No. 61/631,313

U.S. Patent Application No. 61/796,208

Hom_pre2011

Hom_pre2011_header

Hom_pre2011_header_clean

Hom_pre2011.fasta

Ph20_pre2011.aln-clustal_num

Ph20_pre2011 Alignment html

Leisola & Turunen, Protein Engineering: Opportunities and Challenges (2007)

Hecht, De Novo Proteins from Designed Combinatorial Libraries (2004)

Rosengren, Clinical Immunogenicity of rHuPH20 (2015)

Collection of BLAST Webpages from the Internet Archive

Collection of Clustal Omega Webpages from the Internet Archive

Collection of SWISS-MODEL Webpages from the Internet Archive

Collection of PyMol Webpages from the Internet Archive

Declaration of Jeffrey P. Kushan

Swiss Model Printout of PH20 Model

Swiss Model Printout of PH20 Model with S312T Mutation

Swiss Model Printout of PH20 Model with S312N Mutation

Richardson, Science, 240, 1648-1652 (1988)

Doig et al., Protein Science, 4:1325-1336 (1995)

Keedy, PLoS Computational Biology, 8(8):1-10 (August 2012)

Declaration of Dr. Michael Hecht

Declaration of Dr. Sheldon Park

Petition for Post Grant Review

Petitioner's Power of Attorney