NOF Corp v. Nektar Therapeutics

1. Case Identification

• Patent #: [8,273,833](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1003)
• Filed: July 25, 2019
• Petitioner(s): NOF Corp
• Patent Owner(s): Nektar Therapeutics
• Challenged Claims: 1-10

2. Patent Overview

• Title: Branched Reactive Water-Soluble Polymers
• Brief Description: The [’833](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1003) patent relates to branched reactive water-soluble polymers designed for conjugation to biologically active molecules, a process known as PEGylation. The claimed polymers comprise at least two poly(ethylene glycol) (PEG) arms attached through ether linkages to a central aliphatic hydrocarbon core and include a single reactive functional group for attachment to a target molecule.

3. Grounds for Unpatentability

Ground 1: Claims 1-10 are obvious over Bentley

• Prior Art Relied Upon: [Bentley](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1015) (Patent [5,990,237](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1015)).
• Core Argument: Petitioner asserted that Bentley, which was not considered during prosecution despite sharing a common inventor and assignee with the ’833 patent, renders all challenged claims obvious. Bentley was argued to disclose branched PEG polymers for conjugation that inherently meet all structural limitations of claim 1 and teach a molecular weight (MW) range that makes the claimed ranges an obvious selection.
  • Prior Art Mapping: Petitioner argued that Bentley’s disclosed branched PEG aldehyde hydrate polymers map directly onto the claimed Y-(X)p-R(-X'-POLY)q structure. Specifically, Bentley's two RO-(CH2CH2O)mCH2CH2-O- groups are the POLY arms (terminating in hydroxyl or methoxy); the three-carbon glycerol-derived core is the R group (satisfying the at least three-carbon length); the ether linkages are the X' groups; the -O-(CH2)n- linker is the X group; and the terminal aldehyde hydrate group (-CH(OH)2) is the reactive Y group. Petitioner further asserted that Bentley’s disclosure of a “typical” PEG MW range of 200 to 100,000 Da encompasses the entire claimed range of "about 12,000 Da to about 100,000 Da," establishing a prima facie case of obviousness.

Ground 2: Claims 1-10 are obvious over Bentley in view of Harris

• Prior Art Relied Upon: Bentley (Patent 5,990,237) and [Harris](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1016) (Patent [5,932,462](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1016)).
• Core Argument: Petitioner contended that combining the teachings of Bentley with Harris, another Nektar patent in the same field, renders the claims obvious. Harris was said to provide teachings that confirm the benefits of using branched, ether-linked PEG polymers and supplies a strong motivation to select the specific MW ranges recited in the claims to enhance biological properties.
  • Prior Art Mapping: Harris was argued to teach multi-armed, monofunctional polymers with hydrolytically stable linkages, explicitly including ether linkages, for attaching PEG arms (polya, polyb) to a central core.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would be motivated to combine the teachings of the interrelated Bentley and Harris patents to create improved drug conjugates. Harris teaches that using methoxy-capped (mPEG) arms creates monofunctional polymers that avoid undesirable cross-linking and loss of activity, providing a direct rationale to apply mPEG arms to Bentley's structures. Furthermore, Harris demonstrates that a larger, denser "polymer cloud" from higher MW branched polymers (e.g., 40 kDa) improves properties like circulation half-life, motivating a POSA to optimize the Bentley structure to the MWs claimed in the ’833 patent.
  • Expectation of Success: A POSA would have a reasonable expectation of success, as both references operate on the same fundamental principles of PEG chemistry and Harris provides comparative data showing the superiority of the proposed modifications.

Ground 3: Claims 1-5 and 7-10 are obvious over JP-542

• Prior Art Relied Upon: [JP-542](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1017) (Japanese Application Publication No. P2000-1542A).

• Core Argument: Petitioner argued that JP-542, which was not considered during prosecution, independently renders the claims obvious. JP-542 describes branched, multi-arm PEG polymers with a reactive functional group, disclosing all features of the claims or making their selection obvious.

  • Prior Art Mapping: Petitioner mapped the structure of claim 1 onto polymers disclosed in JP-542, such as formula (14). This formula shows a polymer with a central core (R), four PEG arms (POLYs) attached via ether linkages (X'), a six-atom linker (X), and an N-hydroxysuccinimide active ester group (Y), a well-known reactive group. JP-542 was shown to disclose both three-carbon and nine-carbon cores and a total MW range (500 to 176,000 Da) that broadly overlaps with the claimed ranges. Petitioner argued this overlap makes the claimed MW an obvious selection for a POSA seeking to optimize biological performance.
  • Motivation to Combine: This is a single-reference ground. Petitioner argued a POSA would be motivated to select a MW within the claimed range to achieve the explicitly stated goals in JP-542, such as "prolonging a residence time in the body."
  • Expectation of Success: Routine experimentation to optimize the MW for desired properties was argued to be a predictable and successful path for a POSA, given the overlapping ranges and explicit goals disclosed in JP-542.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 1-10 are obvious over Bentley in view of [MDD](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1029) (a publication on optimizing PEG moiety size); claim 6 is obvious over JP-542 in view of Bentley (combining JP-542's polymer core with Bentley's aldehyde chemistry); and claims 1-10 are obvious over JP-542 in view of [Kohno](https://ai-lab.exparte.com/case/ptab/Not Yet Assigned/doc/1027) (a publication teaching MW optimization to improve pharmacokinetics).

4. Key Claim Construction Positions

• Petitioner argued for broad constructions of key claim terms to encompass disclosures in the prior art.
  • "Aliphatic Hydrocarbon": Petitioner contended 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 was asserted as necessary to read the claim onto prior art core structures derived from glycerol, which contains oxygen heteroatoms and is taught in both Bentley and Harris as a suitable core.
  • "functional group": Petitioner argued this term should be understood to mean "the portions of molecules that perform some function or activity and are reactive with other molecules, including protected functional groups." This broad interpretation was used to argue that precursor moieties and protected groups in the prior art, such as the allyl-protected hydroxyl in JP-542, meet this claim limitation.

5. Relief Requested

• Petitioner requested that the Patent Trial and Appeal Board institute an inter partes review and cancel claims 1-10 of Patent 8,273,833 as unpatentable under 35 U.S.C. §103.