NOF Corp v. Nektar Therapeutics

1. Case Identification

• Case #: IPR2019-01397
• Patent #: 9,187,569
• Filed: July 25, 2019
• Petitioner(s): NOF Corporation
• Patent Owner(s): Nektar Therapeutics
• Challenged Claims: 1-12

2. Patent Overview

• Title: Branched Reactive Polymers
• Brief Description: The ’569 patent discloses branched, water-soluble polymers, such as poly(ethylene glycol) (PEG), comprising at least two polymer arms attached to a central aliphatic hydrocarbon core through heteroatom linkages. The polymers are designed for conjugation with biologically active molecules like proteins to improve their therapeutic properties.

3. Grounds for Unpatentability

Ground 1: Obviousness over Harris, alone and in view of Bentley, Choi, and/or Dalborg - Claims 1-12

• Prior Art Relied Upon: Harris (Patent 5,932,462), Bentley (Patent 5,990,237), Choi (WO 99/29759), and Dalborg (WO 97/11957).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Harris alone renders most claims obvious. Harris taught branched, monofunctional, and hydrolytically stable polymers with a structure featuring two mPEG arms linked to an aliphatic hydrocarbon core (lysine) via heteroatom linkages (-NH- or -S-). This structure, Petitioner asserted, met the core limitations of claim 1 regarding the polymer arms (POLY), the core (R), the number of arms (q=2), and the heteroatom linkages (X'). Although Harris’s examples used a carboxyl group as the reactive moiety (Y), it explicitly disclosed that this group could be converted to other reactive moieties, including the claimed maleimide. Harris also taught molecular weights well within the claimed range of 500 to 100,000 Da.
  • Motivation to Combine (for §103 grounds): A POSITA would combine the secondary references to arrive at specific dependent claim limitations. Bentley was introduced because it taught a symmetric, 3-carbon glycerol core structure, making claims 4 and 6 obvious. Choi was combined to render claim 9 (no linker) obvious, as Choi taught a core structure (2-amino-1,3-propandiol) that could form a linkerless polymer, and Harris itself motivated avoiding spacer arms to reduce antigenicity. Dalborg was combined to render claim 12 obvious, as it taught the conjugation of PEG-maleimide polymers specifically to Factor VIII fragments.
  • Expectation of Success: A POSITA would have a reasonable expectation of success as all references operate in the predictable field of PEGylation chemistry, using well-known starting materials and reactions to achieve polymers with desired properties.

Ground 2: Obviousness over Bentley in view of Harris, Choi, and/or Dalborg - Claims 1-12

• Prior Art Relied Upon: Bentley (’237 patent), Harris (’462 patent), Choi (WO 99/29759), and Dalborg (WO 97/11957).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Bentley served as a strong primary reference, disclosing branched PEG polymers that meet nearly all structural elements of claim 1. Bentley taught a polymer with two PEG arms attached to a 3-carbon glycerol core via ether linkages (-O-), which Petitioner mapped to the claimed POLY, R, X', and q limitations. The primary difference was that Bentley’s reactive group (Y) was an aldehyde hydrate, not a maleimide. Petitioner argued that Bentley itself cited the Harris application, acknowledging it as relevant prior art for branched PEG polymers.
  • Motivation to Combine (for §103 grounds): A POSITA would combine Bentley with Harris to replace the aldehyde hydrate functional group with a maleimide. Harris explicitly taught that maleimide was a suitable reactive group for conjugating polymers to proteins, particularly at cysteine residues. A POSITA would be motivated to make this substitution to gain the selectivity of maleimide chemistry. The motivations to further combine Choi (for a linkerless structure) and Dalborg (for conjugation to Factor VIII) were the same as in Ground 1.
  • Expectation of Success: The expectation of success was high, as Harris provided the explicit suggestion to use maleimide functional groups in similar branched polymer systems, and converting an aldehyde to a maleimide involved conventional and predictable chemical techniques.

Ground 3: Obviousness over JP-674 in view of Harris, Choi, and/or Dalborg - Claims 1-7 and 9-12

• Prior Art Relied Upon: JP-674 (Japan Patent Application Publication No. JP-A-2000-44674), Harris (’462 patent), Choi (WO 99/29759), and Dalborg (WO 97/11957).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that JP-674 disclosed branched PEG polymers meeting all structural elements of claim 1 except for the maleimide functional group. The exemplified polymer in JP-674 had a structure with multiple PEG arms on a 3-carbon core, symmetric placement, and a molecular weight of 5,042 Da, falling squarely within the claimed ranges. The structure in JP-674 terminated in a primary amine functional group instead of the claimed maleimide.
  • Motivation to Combine (for §103 grounds): A POSITA would combine JP-674 with Harris because both address the preparation of branched PEG polymers for conjugation. A POSITA would have been motivated to replace the amine group of JP-674 with a maleimide group as taught by Harris to create a polymer selective for thiol groups on a target protein. This simple, known modification would result in the claimed invention. The motivations to add Choi (for a linkerless variant) and Dalborg (for Factor VIII conjugation) remained consistent with the prior grounds.
  • Expectation of Success: A POSITA would reasonably expect success in converting the terminal amine of the JP-674 polymer to a maleimide, as this is a standard, well-documented reaction in bioconjugation chemistry.

4. Key Claim Construction Positions

• "Aliphatic Hydrocarbon": Petitioner argued this term should be construed as "a non-aromatic carbon chain analog, which may be linear or branched, and may include one or more heteroatoms in the chain." This construction, supported by the patent specification, is broader than a pure hydrocarbon and was critical for mapping prior art core structures containing oxygen or nitrogen atoms (like glycerol or lysine) to the claimed "R" group.

5. Relief Requested

• Petitioner requested institution of an IPR and cancellation of claims 1-12 of the ’569 patent as unpatentable.