Non-enablement of Functional Antibody Claims

• Publication year: 2021
• Author: D. Benjamin Borson

NON-ENABLEMENT OF FUNCTIONAL ANTIBODY CLAIMS

D. Benjamin Borson

Borson Law Group P.C.

Amgen et al. v. Sanofi et al, Slip. Op. 2020-1074 (2021).

INTRODUCTION

Amgen owns U.S. Patent No. 8,829,165 (the "'165 patent") and No. 8,859,741 (the "'741 patent"). These patents describe antibodies that purportedly bind to PCSK9 and lower LDL levels by blocking PCSK9 from binding to LDL receptors. This article describes the Federal Circuit's decision in Amgen Inc., Amgen Manufacturing, Limited, and Amgen USA, Inc. v. Sanofi, Aventisub LLC, FKA Aventis Pharmaceuticals Inc., Regeneron Pharmaceuticals Inc., and Sanofi-Aventis U.S. LLC, Slip Op 2020-1074 (11 February 2021) (herein after, "Amgen").

In a decision by Chief Judge Prost, and Circuit Judges Lourie and Hughes, Judge Lourie provided the background of the invention and claims.

Subsequently, amici filed a brief in favor of en banc review of the panel's decision.

BACKGROUND

Elevated low-density lipoprotein ("LDL") cholesterol is linked to heart disease. LDL receptors remove LDL cholesterol from the blood stream, thus regulating the amount of circulating LDL cholesterol. The proprotein convertase subtilisin/kexin type 9 ("PCSK9") enzyme regulates LDL receptor degradation. PCSK9 binds to LDL receptors and mediates their degradation, thus decreasing the number of LDL receptors (LDLR) on a cell's surface. Antibodies may bind to and block PCSK9, allowing LDL receptors to continue regulating the amount of circulating LDL cholesterol. Antibodies of this invention are sold under the generic name, evolocumab, marketed as Repatha.® Slip Op. at page 3 bridging to 4.

The relevant '165 patent claims are:

1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

19. The isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO:3.

29. A pharmaceutical composition comprising an isolated monoclonal antibody, wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3 and blocks the binding of PCSK9 to LDLR by at least 80%.

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The relevant '741 patent claims are:

1. An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

2. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is a neutralizing antibody.

7. The isolated monoclonal antibody of claim 2, wherein the epitope is a functional epitope.

Importantly for this decision, the claimed antibodies of the '741 patent are defined by their function: binding to combinations of sites (residues) on the PCSK9 protein, in a range from one residue to all of them; and blocking the PCSK9/LDLR interaction.

DISTRICT COURT OPINION

Amgen sued Sanofi for infringement of claims of the '165 and '741 patents in the district court in Delaware. At the close of the trial, the jury determined that the patents were not shown to be invalid for lack of enablement and written description under 35 U.S.C. § 112, first paragraph. Sanofi timely appealed to the Court of Appeals for the Federal Circuit (Fed. Cir.) who remanded the case to the district court on the issues of enablement and written description. The jury on remand found that Sanofi failed to prove that the asserted claims were invalid for lack of written description and enablement. Slip Op. at 5.

Sanofi appealed.

The Fed. Cir. remanded the case to review the holdings and Sanofi's defenses. The district court granted Sanofi's Motion for JMOL for lack of enablement and denied the motion for lack of written description. The court also conditionally denied Sanofi's motion for a new trial. Amgen timely appealed.

FEDERAL CIRCUIT OPINION

Writing for the panel, (Chief Judge Prost, and Circuit Judges Lourie and Hughes), Judge Lourie explained the requirement for enablement under 35 U.S.C. § 112, first paragraph:

Whether a claim

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