Antibody Patents in the United States Dan Altman Knobbe Martens Olsen & Bear, LLP Dan Altman Knobbe Martens Olsen & Bear, LLP

Issuance of US Antibody Patents by Year Since 1975…  3,720 total antibody patents issued in the US 1  211 for monoclonal antibodies © 2011 Knobbe Martens Olson & Bear LLP2

3 Three types of antibody claims considered 1.Novel or known target defined by function or use 2.Known target 3.Structural definition

© 2011 Knobbe Martens Olson & Bear LLP4 1. Function or use At least three ways to claim antibodies by function or use: (a) Statement of intended use (b) Antibody “capable of”a function (c)“Method of use” claim

© 2011 Knobbe Martens Olson & Bear LLP5 1. Function or use (a) Statement of intended use: 1. A monoclonal antibody for treating a patient suffering from Disease X.

© 2011 Knobbe Martens Olson & Bear LLP6 1. Function or use 1 Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003) Statement Limits ClaimStatement Does Not Limit Claim Preamble that gives life and meaning to the claim Intended use alone Statement of the intentional purpose for which the method must be performed Statement of effect that may or may not be desired or appreciated (a) Statement of intended use:

© 2011 Knobbe Martens Olson & Bear LLP7 1. Function or use (a) Statement of intended use: 1. A monoclonal antibody for treating a patient suffering from Disease X.

© 2011 Knobbe Martens Olson & Bear LLP8 1. Function or use (a) Statement of intended use [as a claim limitation]: 1.A method of treating or preventing macrocytic- megaloblastic anemia in humans which anemia is caused by either folic acid deficiency or by vitamin B12 deficiency which comprises administering [compound] to a human in need thereof. US Patent # 4,945,083, Jansen et al (Feb 1, 1989)

© 2011 Knobbe Martens Olson & Bear LLP9 (b) Antibodies “capable of” a function 1. A monoclonal antibody capable of neutralizing the DISEASE_X protein. 1. Function or use

© 2011 Knobbe Martens Olson & Bear LLP10 (b) Antibodies “capable of” a function  If antibody is in prior art, burden shifts to applicant to show prior art was not capable of that function See In re Fitzgerald, 619 F.2d 67, 70 (CCPA 1980) 1. Function or use

© 2011 Knobbe Martens Olson & Bear LLP11 (b) Antibodies “capable of” a function: Disclosure of structures may be required  [For] “genus claims that use functional language to define the boundaries of a claimed genus… the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally- defined genus. Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349 (Fed. Cir. 2010) 1. Function or use

© 2011 Knobbe Martens Olson & Bear LLP12 1. Function or use (b) Antibodies “capable of” a function [claim allowed]: 1. An isolated monoclonal antibody that specifically binds an epitope within a polyproline region of the huntingtin protein comprising greater than 5 consecutive proline residues; wherein said antibody is capable of inhibiting aggregation of the huntingtin protein; wherein said monoclonal antibody is a single- chain variant fragment encoded by a nucleotide sequence comprising SEQ ID NO: 5. US Patent # Khoshnan et al (Dec 18, 2003)

© 2011 Knobbe Martens Olson & Bear LLP13 1. Function or use (c) “Method of use” claim: 1. A method of treating Disease X, the method comprising administering to the patient a therapeutically effective amount of monoclonal Antibody A

© 2011 Knobbe Martens Olson & Bear LLP14 1. Function or use (c) “Method of use” claim:  Claiming a new use of a known antibody:  Product claim will be anticipated  But possible “method of use” claim See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999).

© 2011 Knobbe Martens Olson & Bear LLP15 1. Function or use (c) “Method of use” claim:  Identifying new properties or results of a known method of using an antibody:  Method claim will be anticipated  Prior art contains “natural and inherent results in that method.” Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005)

© 2011 Knobbe Martens Olson & Bear LLP16 1. Function or use (c) “Method of use” [claim allowed]: 26. A method of treating a patient suffering from arteriosclerosis, comprising administering to the patient an effective amount of an isolated neutralizing monoclonal antibody, or binding fragment thereof, specific for human oxidized low density lipoprotein receptor (LOX-1). US Patent # Kobiyashi et al. August 9, 2011

Disclosure req’s per US Statute (35 USC 112)  Written description: Specification must prove inventor was in possession of the invention  Enablement: Specification must teach a skilled artisan how to make and use the invention  Best mode: Inventor can’t conceal her contemplated best mode of practicing invention 35 U.S.C. 112 © 2011 Knobbe Martens Olson & Bear LLP17

© 2011 Knobbe Martens Olson & Bear LLP18 2. Known target Claim for an antibody directed against a known target: 1. A monoclonal antibody that specifically binds to the DISEASE_X protein

© 2011 Knobbe Martens Olson & Bear LLP Known target “Antibody exception”: Disclosure of a well- characterized protein generally satisfies the written description requirement (possession)  Inject protein into host animal  raise antibodies  Exception may not apply to human antibodies 1  Ethical issues  Efficacy problems 1 Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1352 (Fed. Cir. 2011)

© 2011 Knobbe Martens Olson & Bear LLP Known target Disclosure of known target can only support claims if: (1) Applicant fully discloses the novel protein; and (2) Generating the claimed antibody is “so routine that possessing the protein places the applicant in possession of an antibody” 1 1 Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1352 (Fed. Cir. 2011)

© 2011 Knobbe Martens Olson & Bear LLP Known target  Adequate disclosure of target: structure, formula, chemical name, physical properties, or depositing protein in a public depository. 1  Inadequate disclosures: 1 Noelle v. Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004) 2 In re Alonso, 545 F.3d 1015, 1021 (Fed. Cir. 2008) ClaimDisclosure Human CD40CR antibody 1 Mouse antigen only Genus of monoclonal antibodies that bind to neurofibrosarcoma (tumor) cells 2 Molecular weight of a single mouse antigen

© 2011 Knobbe Martens Olson & Bear LLP Known target  Known antigen  Monoclonal antibody is prima facie obvious Ex Parte Erlich, 22 U.S.P.Q.2d 1463 (Bd. Pat. App. & Interf. Jan. 16, 1992)  Prima facie showing of obviousness is rebuttable  Inventive process used to make antibody 1  Antibodies exhibit novel specificity for a particular antigen 2 1 e.g. U.S. Patent No. 5,109,115 2 e.g. U.S. Patent No. 5,134,075

© 2011 Knobbe Martens Olson & Bear LLP23 2. Known target Sample Claim [Allowed]: 1. An isolated antibody or fragment thereof that specifically binds to the polypeptide of SEQ ID NO:144. United States Patent # 7,427,664. Goddard, et al. September 23, 2008

© 2011 Knobbe Martens Olson & Bear LLP24 3. Structural claims Claim directed to the antibody structure: 1. A monoclonal antibody comprising an amino acid sequence as set out in SEQ ID 1.

© 2011 Knobbe Martens Olson & Bear LLP25 3. Structural claims Disclosure must prove that every claimed structural element was in inventor’s possession  “The specification at best describes a plan for making fully-human antibodies and then identifying those that satisfy the claim limitations. But a “mere wish or plan” for obtaining the claimed invention is not sufficient.” 1 1 Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1351 (Fed. Cir. 2011)

© 2011 Knobbe Martens Olson & Bear LLP26 3. Structural claims Example of insufficient disclosure: 1 Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1351 (Fed. Cir. 2011) Claimed StructureDisclosed Structure (1) Human Constant RegionHuman constant region (2) Human variable regionMouse variable region (3) High affinity for human TNF-α,High affinity for human TNF-α, (4) Neutralizing activityNeutralizing activity (5) “A2 specificity”A2 specificity     

© 2011 Knobbe Martens Olson & Bear LLP27 3. Structural claims [Allowed structural claim] : 1. An antibody comprising a specific binding member capable of binding an intracellular antigen, wherein said specific binding member comprises a polypeptide binding domain comprising an amino acid sequence as set out as residues 99 to 106 of SEQ ID NO: 2. United States Patent # 6,827,925 Williams et al. December 7, 2004

© 2011 Knobbe Martens Olson & Bear LLP28 3. Structural claims Claim based on deposit of biological material: 1. An isolated monoclonal Antibody A, deposited at Center C on 1 Jan and accorded accession number 123.

© 2011 Knobbe Martens Olson & Bear LLP29 3. Structural claims Limited circumstances under which deposit may satisfy disclosure requirements of 112:  Biological invention  Invention otherwise meets the requirements for patent protection  Providing a description in written form is not practicable Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 970 (Fed. Cir. 2002)

© 2011 Knobbe Martens Olson & Bear LLP30 3. Structural claims  Deposit may satisfy written description requirement 1  Deposit + accession number in specification = possible proof of possession 1 Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 970 (Fed. Cir. 2002)

© 2011 Knobbe Martens Olson & Bear LLP31 3. Structural claims  Deposit usually sufficient to satisfy enablement requirement 1  Deposit not always necessary to satisfy enablement requirement 2 1 Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 965 (Fed. Cir. 2002) 2 In re Wands, 858 F.2d 731, 736 (Fed. Cir. 1988); See also 37 CFR Part 1

© 2011 Knobbe Martens Olson & Bear LLP32 3. Structural claims  For genus claims, deposit must represent scope of claim Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 (Fed. Cir. 2002)

© 2011 Knobbe Martens Olson & Bear LLP33 3. Structural claims Deposits and best mode  Best mode requirement: Inventor cannot conceal subjective “best mode”  No deposit required when: “[The invention] can be prepared by one skilled in the art from known materials using the description in the specification.” Amgen, Inc. v. Chugai Pharm. Co., Ltd., 927 F.2d 1200, 1211 (Fed. Cir. 1991)

© 2011 Knobbe Martens Olson & Bear LLP34 3. Structural claims Claim based on deposit of biological material [Allowed]: 1. An isolated monoclonal antibody mAb PAB-1, deposited at ATCC on 24 Jan and accorded accession PTA-4005, which binds to a surface antigen on nematode L3. United States Patent # 7,326,774 Harrison, et al. February 5, 2008

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