Bioactive Laboratories v. BTG International Inc.

1. Case Identification

• Patent #: 8,048,414
• Filed: May 29, 2015
• Petitioner(s): Bioactive Laboratories
• Patent Owner(s): BTG International Inc.
• Challenged Claims: 1-22

2. Patent Overview

• Title: Antivenom Composition Containing Fab Fragments
• Brief Description: The ’414 patent is directed to antivenom pharmaceutical compositions comprising antibody Fab fragments for treating snake bites from snakes of the Crotalus genus (rattlesnakes), and methods of using the same. The invention also relates to purifying these Fab fragments for therapeutic use.

3. Grounds for Unpatentability

Ground 1: Anticipation over the ’352 Patent - Claims 1-7, 9-18, 21, and 22 are unpatentable under 35 U.S.C. §102 as anticipated by the ’352 Patent.

• Prior Art Relied Upon: Patent 4,849,352 ("the ’352 patent").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner’s primary argument was that the ’414 patent was not entitled to its claimed priority date. Petitioner contended that the priority applications failed to meet the written description and enablement requirements of §112 for the full scope of the challenged claims. As a result, the ’352 patent, which issued in 1989 and was part of the invalid priority chain, qualified as prior art under §102(b) against the ’414 patent’s effective filing date of March 15, 1995. Petitioner argued that the disclosure of the ’352 patent, which is identical to the specification of the ’414 patent, explicitly described every element of the challenged claims. For example, for claim 1, the ’352 patent allegedly disclosed an antivenom composition with Fab fragments that bind specifically to Crotalus venom, is essentially free of contaminating Fc, includes a carrier, and neutralizes the venom’s lethality.
  • Key Aspects: The central thrust of this ground was not a direct comparison of disclosures but a legal argument to invalidate the ’414 patent’s priority claim, thereby re-classifying the ’352 patent as anticipating prior art.

Ground 2: Obviousness over Chang and WHO Report - Claims 1-7, 9-18, and 20-22 are obvious over Chang in view of the WHO Report.

• Prior Art Relied Upon: Chang, C.C. and Yang, C.C. "Immunochemical Studies on Cobrotoxin," 102 J. Immunology 1437-1444 (1969) (“Chang”); and "WHO Progress in the Characterization and Standardization of Antivenoms" WHO Offset Publication 3-44 (1981) (“WHO Report”).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Chang taught all key elements of the invention except for its application to Crotalus venom. Specifically, Chang disclosed an effective antivenom composition comprising papain-produced Fab fragments that were essentially free of contaminating Fc fragments and neutralized the lethality of cobra venom. The WHO Report, a comprehensive review of antivenoms, identified snakes of the Crotalus genus as "Medically Important Snake Species," establishing them as a known and important target for antivenom development. The combination of Chang and the WHO Report allegedly taught every limitation of the independent claims.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine these references to apply the known benefits of Chang's Fab-based antivenom (e.g., reduced risk of serum sickness) to the well-recognized clinical need for treating bites from Crotalus snakes, as highlighted by the WHO Report. This was presented as a straightforward application of a known, advantageous technique to a known problem.
  • Expectation of Success: A POSA would have a reasonable expectation of success because applying the established biochemical methods for creating Fab antivenom from one snake species (cobra) to another (rattlesnake) was a predictable extension of the technology.

Ground 3: Obviousness over Chang, WHO Report, and Smith - Claims 8 and 19 are obvious over Chang in view of the WHO Report and Smith.

• Prior Art Relied Upon: Chang (1969); WHO Report (1981); and Smith, T.W., et al., "Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments..." 36 Clin. Exp. Immunology 384-396 (1979) (“Smith”).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground specifically addressed claims 8 and 19, which require a composition comprising both Fab and F(ab’)2 fragments. Building on the Chang/WHO combination, Petitioner introduced Smith to provide the rationale for combining different antibody fragments. Smith disclosed the distinct pharmacokinetic properties of Fab fragments (rapid onset, rapid clearance) and F(ab’)2 fragments (longer half-life, more sustained effect).
  • Motivation to Combine: A POSA would be motivated to combine Fab fragments with F(ab’)2 fragments to create an improved antivenom. The combination would leverage the rapid neutralization and distribution of Fab fragments for an immediate effect, while the longer half-life of F(ab’)2 fragments would provide sustained control over the venom's toxic effects, potentially reducing the need for frequent redosing.
  • Expectation of Success: Success was expected because the fragments were known to have distinct, non-interfering pharmacokinetic profiles. A POSA would anticipate that they would exert their respective therapeutic effects when co-administered.

4. Key Claim Construction Positions

• "Essentially free from contaminating Fc": Petitioner argued this term should be construed to mean "not more than small, detectable levels of Fc," and critically, that "contaminating Fc" includes both free Fc fragments and the Fc portions of intact IgG molecules. Petitioner contended this construction was necessary because the invention’s goal was to create a safer antivenom by removing the Fc region, which causes serum sickness, regardless of whether it is a separate fragment or part of a whole antibody.
• "Binds to" and "bind specifically to": Petitioner argued for a distinction based on claim differentiation. The term "bind specifically to" (e.g., in claim 1) was argued to be narrower, meaning the fragments only bind to Crotalus venom and not other antigens. In contrast, "binds to" (in claim 19) was argued to be broader, referring to the basic ability to interact with the venom. This distinction was central to Petitioner's argument that the priority applications lacked written description for the broader, non-specific binding of claim 19.
• "neutralizes the lethality of the venom...": Petitioner argued this phrase means the entire claimed composition, when administered, must have a significant effect on patient mortality. This was contrasted with the Patent Owner’s alleged position that the Fab fragments themselves must be the component responsible for neutralization. Petitioner used this broader construction to argue that the claims lacked written description and enablement in the priority applications, as those documents only described compositions where the antibody fragments were the active neutralizing agent.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-22 of the ’414 patent as unpatentable.