1:16-cv-01580
Halozyme Inc v. Lee
I. Executive Summary and Procedural Information
Parties & Counsel:
- Plaintiff: Halozyme, Inc. (California)
- Defendant: Joseph Matal, performing the functions and duties of Under Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark Office (Alexandria, VA)
- Plaintiff’s Counsel: McDermott Will & Emery LLP
Case Identification: 1:16-cv-01580, E.D. Va., 07/03/2017
Venue Allegations: Venue is alleged to be proper in the Eastern District of Virginia pursuant to 35 U.S.C. § 145.
Core Dispute: Plaintiff appeals a final decision by the Patent Trial and Appeal Board that affirmed the rejection of certain claims in its patent application, seeking a judgment that it is entitled to a patent for the rejected claims.
Technical Context: The technology involves modifying a human-derived enzyme, hyaluronidase, with polyethylene glycol (PEG) to improve its therapeutic properties, such as increasing its circulation time in the body.
Key Procedural History: The U.S. Patent and Trademark Office (USPTO) issued a Final Rejection of claims in Plaintiff’s patent application. Plaintiff appealed to the Patent Trial and Appeal Board (PTAB), which affirmed the examiner's rejection on grounds of obviousness. The PTAB subsequently denied a request for rehearing, making its decision final and triggering this civil action under 35 U.S.C. § 145.
Case Timeline
| Date | Event |
|---|---|
| 2005-02-23 | Priority Date for U.S. Patent Application No. 11/238,171 |
| 2012-08-20 | USPTO issues Final Rejection of claims |
| 2012-12-20 | Plaintiff files Notice of Appeal to the PTAB |
| 2016-07-27 | PTAB issues Decision on Appeal affirming rejection |
| 2016-10-20 | PTAB denies Request for Rehearing |
| 2017-07-03 | First Amended Complaint filed |
II. Technology and Application-in-Suit Analysis
Application Identification
- U.S. Patent Application Serial No. 11/238,171, titled "Soluble Glycosaminoglycanases and Methods of Preparing and Using Soluble Glycosaminoglycanases" ('171 Application) (Compl. ¶1, 21).
The Invention Explained
- Problem Addressed: Naturally occurring human-derived hyaluronidase, an enzyme that degrades hyaluronan, is rapidly cleared from systemic circulation. This short duration prevents it from effectively reaching and breaking down hyaluronan barriers associated with tumor masses, limiting its therapeutic potential (Compl. ¶15, 18).
- The Patented Solution: The invention is a pharmaceutical composition in which the human-derived hyaluronidase enzyme is modified by attaching three to six polyethylene glycol (PEG) moieties to its lysine residues. This modification, known as PEGylation, is alleged to make the enzyme soluble and enzymatically active at neutral pH, allowing it to circulate in the body longer and reach tumor masses (Compl. ¶10, 20).
- Technical Importance: This specific modification was intended to increase the enzyme's half-life and overcome clearance by the reticuloendothelial system, thereby improving its ability to aid in drug delivery and cancer treatment (Compl. ¶16, 18).
Key Claims at a Glance
- The complaint identifies the rejected claims at issue as Claims 264, 295-298, 300, and 303 (Compl. ¶1).
- The complaint does not provide the full text of the asserted rejected claims for analysis. It describes the invention generally as a pharmaceutical composition comprising a "human-derived hyaluronidase" that contains "three to six pendant moieties of polyethylene glycol (PEG) per hyaluronidase" (Compl. ¶10).
III. Analysis of Arguments Against Rejection
The central dispute in this case is not patent infringement, but rather an appeal of the PTAB's decision to affirm the rejection of the '171 Application's claims. The complaint sets forth Halozyme's arguments that the PTAB's decision was legally and factually erroneous (Compl. ¶27, 29).
Basis for Rejection
The PTAB affirmed the USPTO examiner's rejection of the pending claims on two grounds:
- Obviousness under 35 U.S.C. § 103(a): The claims were deemed obvious over a combination of three prior art references: Bookbinder et al. (WO 2004/078140), Braxton (U.S. Patent No. 5,766,897), and Thompson et al. (U.S. Patent No. 6,552,170) (Compl. ¶28).
- Obviousness-Type Double Patenting: This rejection was based on several existing U.S. patents in view of the Braxton and Thompson references (Compl. ¶28).
Plaintiff's Arguments on Appeal
The complaint alleges the PTAB erred for several reasons:
- Improper Prior Art: The complaint argues that the "Bookbinder" reference is not prior art under 35 U.S.C. § 102 because the inventors are the same as those on the '171 Application and the application is entitled to a priority date preceding Bookbinder's publication (Compl. ¶30).
- Teaching Away: The complaint alleges that the Braxton and Thompson references teach away from the claimed invention. It asserts these references teach PEG conjugation specifically to cysteine residues with a preference for attaching only a single PEG moiety ("mono-PEGylation"). Halozyme argues this is "inapplicable to the present invention of PEG-hyaluronidase compositions" which are modified on lysine residues with three to six PEG moieties, and that applying the prior art's teachings would have been expected to destroy the enzyme's function (Compl. ¶31, 35.e).
- Lack of Motivation to Combine: The complaint contends that even if a skilled artisan were to consider PEGylating hyaluronidase, there is nothing in Braxton and Thompson that would have motivated them to seek out the specific, narrow range of "three to six PEG moieties attached to the lysine residues" of the enzyme (Compl. ¶32).
- Erroneous Factual Findings: The complaint asserts that the PTAB's finding of obviousness was based on flawed factual findings that "do not withstand scrutiny," such as misinterpreting the teachings of the prior art references regarding the type of enzyme modified and the specific chemistry of PEGylation taught (Compl. ¶35). Specifically, it is alleged that the PTAB failed to appreciate that Braxton and Thompson teach a different type of PEGylation (cysteine-directed) from that claimed (lysine-directed) (Compl. ¶35.e).
- Routine Optimization: The complaint argues that the PTAB's characterization of the invention as "routine optimization" is without evidentiary support, given the unpredictability of PEGylating a large glycoprotein like hyaluronidase (Compl. ¶33, 34.e).
No probative visual evidence provided in complaint.
IV. Analyst’s Conclusion: Key Questions for the Case
This action presents a de novo review of the PTAB's decision, allowing the Plaintiff to introduce new evidence not of record at the USPTO (Compl. ¶34). The case will likely turn on the court's determination of the following open questions:
- A central legal issue will be one of prior art status: Does the Bookbinder reference, which shares inventors with the '171 Application, qualify as prior art under 35 U.S.C. § 102 for the purposes of an obviousness analysis under § 103, or did the PTAB err in considering it?
- A key factual question will be the scope and teachings of the prior art: Do the Braxton and Thompson references, which allegedly teach cysteine-directed mono-PEGylation, provide a motivation for a person of ordinary skill to pursue the claimed invention—lysine-directed PEGylation with three to six moieties—or do they, as the Plaintiff alleges, teach away from it?
- An ultimate question for the court will be one of obviousness versus invention: Was the discovery of the specific 3-6 PEG moiety range for modifying hyaluronidase a matter of "routine optimization" as the PTAB found, or did it solve specific, unpredictable technical challenges in a way that would not have been obvious to a skilled artisan at the time?