2017 01-25 uwls-apl_biotech 112

transcript

Biotechnology Patents: Disclosure Requirements

under 35 USC § 112University of Washington

School of LawGary M. Myles, Ph.D.

January 25, 2017(425) 466-8262

gary@mylesip.com

Topics Covered35 U.S.C. § 112

Enablement and Written Description• In Re Wright (Fed. Cir. 1993)• U. of California v. Eli Lilly (Fed. Cir. 1997)• Enzo v. Gen-Probe (Fed. Cir. 2002), Rader

Dissent• Chiron v. Genentech (Fed. Cir. 2004)• Rochester v. Searle (Fed. Cir. 2004)• Ariad v. Lilly (Fed. Cir. 2009), (Fed. Cir., en

banc, 2010)

• 35 U.S.C. § 101, Utility– Specific, Substantial, and Credible

• 35 U.S.C. § 112, Specification–Enablement–Written Description–Best Mode

The Statutory Patent Disclosure Requirements

PRE-AIA35 U.S.C. § 112, ¶ 1

The SPECIFICATION shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains … to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

POST-AIA35 U.S.C. § 112(a)

(a) In General.— The SPECIFICATION shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains … to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out [[his]] the invention.

Enablement – Basic ConceptsA patent application must provide

sufficient disclosure to enable a person skilled in the art to make and use the claimed invention

One skilled in the art would be enabled to practice the claimed invention if:• It would NOT require “undue

experimentation” to make and use the claimed invention

• The claims are NOT of “undue breadth” in view of the scope of the disclosure provided by the specification

Enablement – Basic Concepts In re Wands (Fed. Cir. 1988): “The key

word is ‘undue,’ not ‘experimentation’ ” Quoting In re Angstadt (CCPA 1976)• Quantity of experimentation• Amount of direction and guidance

provided• Presence or absence of working

examples• Nature of the invention• State of the prior art• Relative skill of those in the art• Predictability of the art• Breadth of the claims

The Problem of Enablement in Biotechnology

What is the scope of protection afforded by these claims?• A cDNA encoding Protein X, comprising the

nucleotide sequence of SEQ ID NO: 1. (wherein SEQ ID NO: 1 encodes full-length Protein X)

• A cDNA encoding Protein X, comprising a nucleotide sequence that is at least 70% identical to the nucleotide sequence of SEQ ID NO: 1.

How easy would it be for a third-party competitor to escape the literal scope of these claims by “designing around” with insubstantial nucleotide substitutions?

Degeneracy of the Genetic Code

T C A G

TTTT Phe (F)TTC " TTA Leu (L)TTG "

TCT Ser (S)TCC " TCA " TCG "

TAT Tyr (Y)TAC TAA Ter TAG Ter

TGT Cys (C)TGC TGA Ter TGG Trp (W)

CCTT Leu (L)CTC " CTA " CTG "

CCT Pro (P)CCC " CCA " CCG "

CAT His (H)CAC " CAA Gln (Q)CAG "

CGT Arg (R)CGC " CGA " CGG "

AATT Ile (I)ATC " ATA " ATG Met (M)

ACT Thr (T)ACC " ACA " ACG "

AAT Asn (N)AAC " AAA Lys (K)AAG "

AGT Ser (S)AGC " AGA Arg (R)AGG "

GGTT Val (V)GTC " GTA " GTG "

GCT Ala (A)GCC " GCA " GCG "

GAT Asp (D)GAC " GAA Glu (E)GAG "

GGT Gly (G)GGC " GGA " GGG "

Amgen v. Chugai (Fed. Cir. 1991)Teach how to make and use the claimed

invention such that it can be practiced by a person of skill in the art without undue experimentation• Disclosure that is commensurate in

scope with the breadth of the claims• Multiple working examples within the

claim scope• Teaching of how to test additional

undisclosed variants within the claim scope

Amgen v. Chugai (Fed. Cir. 1991)Make and Use Without Undue

Experimentation• Structural Limitations

−Provide algorithms for computing percent identity

−Describe conservative amino acid substitutions

• Functional Limitations−Disclose assay systems and

methodologies for confirming claimed functionality

In Re Wright (Fed. Cir. 1993)

Claim 11A live, non-pathogenic vaccine for a pathogenic RNA virus, comprising an immunologically effective amount of a viral antigenic, genomic expression having an antigenic determinant region of the RNA virus, but no pathogenic properties.

One Working Example• A recombinant vaccine that confers

immunity in chickens against Prague Avian Sarcoma Virus (PrASV), which is an RNA virus that is a member of the Rous Associated Virus (RAV) family

In Re Wright (Fed. Cir. 1993)Federal Circuit

• “… claims are directed to vaccines, and methods of making and using these vaccines, which must by definition trigger an immunoprotective response in the host vaccinated; mere antigenic response is not enough”

Federal Circuit• “Wright has failed to establish by

evidence or arguments that, in February of 1983, a skilled scientist would have believed reasonably that Wright’s success with a particular strain of an avian RNA virus could be extrapolated with a reasonable expectation of success** to other avian RNA viruses.”

**QUERY: Is “reasonable expectation of success” a test for enablement?

Enablement

General Rules• Broad scope requires broad disclosure• Working examples not required• Not required to teach “and preferably

omits” what is well known in the art”(Hybritech v. Monoclonal Antibodies (Fed. Cir. 1986))

EnablementHistorically …

• Enablement was the most onerous disclosure requirement under 35 USC § 112, first paragraph

UCalifornia v. Eli Lilly (Fed. Cir. 1997)UC disclosed:

• Cloned a cDNA encoding rat insulin• Determined the rat cDNA nucleotide

sequence• Amino acid sequence of human insulin

protein• General method for obtaining the human

UC v. Eli Lilly (Fed. Cir. 1997)

UC claimed:1. A recombinant plasmid replicable in procaryotic host containing within its nucleotide sequence a subsequence having the structure of the reverse transcript of an mRNA of a vertebrate, which mRNA encodes insulin.5. A recombinant procaryotic microorganism modified so that it contains a nucleotide sequence having the structure of the reverse transcript of an mRNA of a human, which mRNA encodes insulin.

UC v. Lilly (Fed. Cir. 1997)District Court

• Held claims invalid under § 112, ¶ 1, because “the specification, although it provided an adequate written description of rat cDNA, did not provide an adequate written description of the cDNA required by the asserted claims.”

UC v. Lilly (Fed. Cir. 1997)Federal Circuit Upholds District Court

• Claim 1 invalid−A description of rat insulin cDNA is not a

description of the broad classes [genra] of vertebrate or mammalian insulin cDNA

−A description of a chemical genus ‘requires a precise definition, such as by structure, formula, [or] chemical name.’ Quoting, Fiers v. Revel 984 F.2d at 1171

• Claim 5 invalid−“whether or not [Example 6] provides an

enabling disclosure, it does not provide a written description of the cDNA encoding human insulin.”

UC v. Lilly (Fed. Cir. 1997)Written description becomes a super-

enablement requirement, which is separate and apart from the enablement requirement

Enzo v. Gen-Probe (Fed. Cir. 2002)

Rader dissent• UC v. Lilly (1997) was a “deviation from

30 years of precedent”• Fed. Cir., for the first time, “purported to

apply WD as a general disclosure doctrine in place of enablement, rather than as a priority doctrine.”

Enzo v. Gen-Probe (Fed. Cir. 2002)Rader Dissent

• History of the Written Description Requirement−“Written description” first appears in

Patent Act of 1793−Evans v. Eaton (1822), S. Ct.

construed description requirement to be an enablement requirement

−JEM AG Supply (2001), S. Ct. acknowledged only enablement as the disclosure quid pro quo of Patent Act

The Priority Claim35 U.S.C § 120. Benefit of Earlier Filing

Date in the United States• “An application for patent for an

invention disclosed in the manner provided by the first paragraph of section 112 of this title in an application previously filed in the United States … shall have the same effect, as to such invention, as though filed on the date of the prior application.”

What Does 35 U.S.C. § 120 Mean?

A claim in a CON or CIP, which claims priority to a parent application, is valid under 35 U.S.C. § 112, ¶1 if the priority application: • Is enabling (make and use) of the claim• Provides written description

(possession) support for the claimSupports a policy of providing broad

protection for pioneering inventions

Historical Perspective onContinuation Practice

Pre-GATT• Before June 7, 1995, when US patent

term was 17 years from date of issue, continuations (CONs), and continuations-in-part (CIPs) attractive

• Submarine Patents−Inventor Lemelson−Policy/fairness concerns

17 YRS17 YRS

17 YRS

Post-GATT• Since June 8, 1995, US patent term is

20 years from date of first filing, making CONs and CIPs less attractive

20 YRS from 1st filed application

Historical Perspective onContinuation Practice

Chiron v. Genentech (Fed. Cir. 2004)

Feb. 1984 Parent App. Filed Discl. 1 MAbNo ChimericNo Humanized

May 1984First ChimericAntibody Publication

1985 CIP App. FiledDiscl. 6 MAbNo Chimeric No Humanized

1986 CIP App. FiledDiscl. 6 MAbNo ChimericNo Humanized

1995 CIPApp. FiledDiscl. 1 MAbChimeric & Humanized Ab Technology

May 1986First HumanizedAntibody Publication

Intervening Art1977First MonoclonalAntibody Publication

‘561 patent issues with claims directed to monoclonal antibodies that bind to HER-2 (an antigen associated with breast cancer)

Chiron sues Genentech for infringement over sales of Herceptin®, a humanized Ab that binds to HER-2

Claims construed to encompass chimeric and humanized antibodies to HER-2, in addition to the murine antibodies disclosed in the 1984, 1985, 1986, and 1995 applications

Parties stipulate that if Chiron is not entitled to a priority claim under 35 U.S.C § 120, the intervening art anticipates the ‘561 patent claims

Feb. 1984 Parent App. Filed Discl. 1 MAbNo ChimericNo Humanized(HELD: NO WD)

May 1984First ChimericAntibody Publication

1985 CIP App. FiledDiscl. 6 MAbNo Chimeric No Humanized(HELD: NON-ENABLED)

1986 CIP App. FiledDiscl. 6 MAbNo ChimericNo Humanized(HELD: NON-ENABLED)

1995 CIP (‘561 Patent) App. FiledDiscl. 1 MAbChimeric & Humanized Ab Technology(HELD: ANTICIPATED)

May 1986First HumanizedAntibody Publication

Chiron sues GenentechFor Infringement based on sale of Herceptin(Humanized Ab)

Intervening Art1977First MonoclonalAntibody Publication

Chiron v. Genentech (Fed. Cir. 2004)Fed. Cir.’s Reasoning

• The 1985 and 1986 applications do not enable the ‘561 patent claims because:−Chimeric Abs were “nascent technology

requiring a ‘specific and useful teaching.’ ”

−Undue experimentation required to make and use the claimed chimeric antibodies

−Enabling disclosure must be commensurate in scope with claims

◦Claim reads on chimeric and murine Abs, yet applications do not disclose chimeric Abs

Fed. Cir.’s Reasoning, cont.• The 1984 application does not provide

written description support for the ‘561 patent claims because:−No disclosure, hence possession, of chimeric

or humanized Ab technologies−Enablement requirement does not apply to

after-arising technologies

After-Arising Technologies: Lingering Questions Post-Chiron

OriginalApplication

Invalid

After-Arising Technology

Continuation

• Would the outcome in Chiron had been different if:

• The original application had matured into a patent?

• If the subsequent application had been a CON rather than a CIP?

Prior Art

U. of Rochester v. Searle (Fed. Cir. 2004)

Rochester Discloses• COX-2 gene and protein• COX-2 is expressed in response to

inflammatory stimuli and is associated with arthritis

• Screening of compounds to see if they are capable of selectively inhibiting COX-2

• No actual disclosure of any COX-2 inhibitors

Rochester claims• Methods for selectively inhibiting [COX-

2] activity in a human host, comprising administering a non-steroidal compound that selectively inhibits activity of the [COX-2] gene product to a human host in need of such treatment

Searle sued for sale of COX-2 inhibitors Celebrex® and Bextra®, marketed for treatment of inflammation

Fed. Cir. upholds invalidity of claims for lack of written description.• “[T]he ‘850 patent does not disclose

any compounds that can be used in its claimed methods. The claimed methods thus cannot be practiced based on the patent’s specification, even considering the knowledge of one skilled in the art.”

Ariad v. Lilly (Fed. Cir. 2009)Ariad Claims:

95. [A method for reducing, in eukaryotic cells, the level of expression of genes which are activated by extracellular influences which induce NF-κB-mediated intracellular signaling, the method comprising reducing NF-κB activity in the cells such that expression of said genes is reduced], carried out on human cells.

Ariad v. Lilly (Fed. Cir. 2009)Ariad Disclosed:

• Three classes of molecules (by function, not structure)−Specific Inhibitors−Dominantly interfering molecules−Decoy molecules

Ariad v. Lilly (Fed. Cir. 2009)District Court

• Held claims infringed and not invalid for anticipation, lack of enablement, and lack of written description

Ariad v. Lilly (Fed. Cir. 2009)Federal Circuit

• “Regardless of whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods. … the specification suggests only the use of the three classes of molecules*** to achieve NF-κB reduction.”

*** The three classes of molecules include−Specific Inhibitors−Dominantly interfering molecules−Decoy molecules

“Thus, to satisfy the written description requirement for the asserted claims, the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-κB activity.” Citing, Capon v. Eshhar (Fed. Cir. 2005)

“A vague functional description and an invitation for further research does not constitute written disclosure of a specific inhibitor.

* * *written description requires more than a ‘mere wish or plan for obtaining the claimed chemical invention.’ ” UC v. Eli Lilly

Ariad v. Lilly (Fed. Cir. 2009) Federal Circuit

• Judge Linn’s Concurrance“I write separately to emphasize … my

belief that our engrafting of a separate written description requirement onto 35 USC 112, paragraph 1 is misguided.

* * *[S]ection 112, paragraph 1 requires no more of the specification than a disclosure that is sufficient to enable a person having ordinary skill in the art to make and use the invention.”

Ariad v. Lilly (Fed. Cir. 2009)Ariad appeals to Federal Circuit for en banc

review• Whether 35 U.S.C. § 112, ¶ 1, contains a

written description requirement separate from an enablement requirement

• If a separate written description requirement is set forth in the statute, what is the scope and purpose of the requirement?

On August 21, 2009, Federal Circuit grants en banc review, vacating the court’s April 3, 2009 opinion

Ariad v. Lilly (Fed. Cir. 2010) (en banc)

Federal Circuit• Opinion joined by every member of the

Court except Linn and Rader• Reaffirms that there is a separate

written description and enablement requirement under 35 USC § 112, first paragraph

A separate written description requirement “plays a vital role in curtailing claims that do not require undue experimentation to make and use, and thus satisfy enablement, but that have not been invented**, and thus cannot be described.”

And “particularly for the biological arts,” having a separate written description requirement “ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function.”

“Generic claim language appearing in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus clamed.”

“A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But 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.”

In Summary … 35 U.S.C. § 112 (a) -- Specification

• Enablement−Teach one skilled in the art−Make and use the claimed invention−Without undue experimentation−Disclose nascent technology

• Written Description−Demonstrate Applicant’s possession of the

claimed invention−Provide disclosure of structure, formula,

chemical name, or physical properties

Practice TipDisclosure of Single Embodiments is

Claim Construction

35 U.S.C. § 112 (a)

OK if construed reads on:· Your commercial product· Competitor’s commercial product

“Invalid”

Practice TipDisclose Multiple Embodiments

Claim Construction

35 U.S.C. § 112 (a)

“Not Invalid”

Practice TipDraft Nested Claims from Broad to

Narrow

1. Broad Independent Claim

2. Narrow Dependent Claim

3. Still Narrower Dependent Claim

4. Narrowest “Picture” Claim

Stay Tuned …

Thank You!Gary M. Myles, Ph.D.gary@mylesip.com

(425) 466-8262