biotechnology novelty and nonobviousness 14 sep10

Biotechnology Patent Prosecution – Part 1 Novelty and Nonobviousness

Gary M. Myles, Ph.D.Biotechnology and the LawSeattle University School of LawSeptember 14, 2010

The Statutory Requirements for Patentability

Prior Art– 35 U.S.C. § 102 Novelty

Single reference Discloses every element of claimed invention

– 35 U.S.C. § 103 Non-obviousness Multiple references Predictability Motivation to combine Teach or suggest claimed invention Reasonable expectation of success

The Statutory Requirements for Patentability

Disclosure Requirements– 35 U.S.C. § 101 Patentability/Utility

Statutory subject matter Specific, substantial, and credible utility

– 35 U.S.C. § 112, ¶ 1 Specification Enablement Written Description Best Mode

Novelty and Staturory Bars

35 U.S.C. § 102 -- Conditions for patentability; novelty and loss of right to patent A person shall be entitled to a patent unless - (a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for patent, or (b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of the application for patent in the United States, or …

Novelty (102(a), (e) and (g))

Novelty is keyed to the time the inventor completed the invention – the “invention date”– Only the first inventor can obtain a patent

regardless of whether a later inventor filed an earlier application on the same technology

– Based on the “first to invent” priority system unique to the US

Statutory Bars (102(b) and (d))

Statutory bars are keyed to the day on which the inventor submitted an application to the USPTO – the “filing date”

– The point in time one year prior to the filing date is the “critical date”

– Publications or sales bar an applicant from obtaining a patent if they occur before the “critical date”

– 102(b) provides a one-year “grace period” which allows an inventor to determine whether patent protection is desirable Can publish an article and file a patent application within one

year

The Test for Novelty

For Novelty– A single prior art reference ANTICIPATES if that

reference discloses – either expressly or inherently -- each element of the claimed invention

– To ANTICIPATE, a prior art reference must enable one of ordinary skill in the art to make and use the claimed invention

Inherent Anticipation

A prior art reference cited under §102 may inherently, rather than expressly, anticipate the claimed subject matter


Ex parte Novitski (BPAI 1993)– Claims

Directed to a method of protecting a plant from nematodes comprising inoculating a plant with a strain of Pseudomonas

– Prior art Taught inoculation of plants with the same strain of

Pseudomonas for protecting a plant from fungal disease. Did not expressly disclose the nematodal activity of the strain

or a method of protecting a plant from nematodes.– Held

Board found that the strain inherently possessed nematode-inhibiting activity and thus the reference “inherently and necessarily” constituted the claimed method


Elan v. Mayo (Fed. Cir. 2000)– District Court Held

A patent that prophetically disclosed a method for creating a transgenic mouse that expresses a human protein associated with Alzheimer’s disease inherently anticipated Elan’s claims to a transgenic mouse that expresses the protein in detectable amounts even though the prior art patent specification did not disclose that the resulting mouse expressed the protein

– Federal Circuit Reverses “Invalidation based on inherency is not established by

probabilities” The prior art was viewed as “an invitation to experiment, with

no assurance of success”


Schering v. Geneva (Rader; Fed. Cir. 2003)– Geneva challenged the validity of Schering’s

patent, which claims the antihistamine DCL -- a metabolite of loratadine (ClaritinTM)

– An earlier Schering patent disclosed that loratidine could be used as an antihistamine but did not disclose that loratidine is metabolized to DCL in vivo


Schering v. Geneva, cont.– Geneva alleged that Schering’s prior art teaching

“inherently anticipated” Schering’s claims to DCL– Schering argued that the claims are not inherently

anticipated because Geneva did not identify prior art evidence demonstrating “prior recognition” that loratidine converts to DCL


Schering v. Geneva, cont.– Federal Circuit Upholds Invalidity

A chemical or pharmaceutical composition is inherent in the prior art if it is a “necessary and inevitable” consequence of the disclosure in a prior art reference

“recognition … before the critical date … is not required to show anticipation by inherency”

Impact on Patent Prosecution

General goal is to obtain as broad a claim as possible in view of the prior art

– This means reducing the number of limitations If the only difference between a claim and a prior art

reference is a single claim limitation – Must ensure that claim limitation is missing from the prior

art Expressly Inherently

– Post-filing evidence of that claim limitation in the prior art can invalidate a patent if that limitation is “necessary and inevitable” even though it was not “recognized” as of the critical date

Non-obviousness

35 U.S.C. § 103 - Conditions for patentability; non-obvious subject matter(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.

http://www4.law.cornell.edu/uscode/35/102.html

Evolution of Modern Obviousness

Hotchkiss v. Greenwood (S. Ct. 1850)– Invalidated patent because it involved only a

substitution of materials rather than any real innovation

– Added the requirement of nonobviousness, which had been left to the courts by Congress, requiring an examination of the subject matter of the patent and the background skill of the trade involved

Patent Act of 1952– Added 35 U.S.C. § 103, the statutory requirement of

nonobviousness– Compare the subject matter sought to be patented

and the prior art, in order to determine whether or not the subject matter of the patent would have been obvious at the time the invention was made to a person having ordinary skill in the art (PHOSITA)


Graham v. John Deere (S. Ct. 1966)– Thomas Jefferson intended

Limited monopoly granted by a patent was only to be permitted for those inventions which were new, useful, and furthered human knowledge

NOT for small details and obvious improvements

– 4 Factors to Determine Obviousness Scope and content of the prior art Differences between the prior art and the claims Level of ordinary skill in the art Evidence of secondary considerations

– Long-felt but unsolved need– Commercial success– Failure of others


United States v. Adams (S. Ct. 1966)– Nonobviousness found where “operating

characteristics” would have been unexpected and far surpassed prior art

– Even though each of the elements was well known in the prior art, long-accepted factors would have deterred any investigation into such a combination “[K]nown disadvantages in old devices which would

naturally discourage the search for new inventions may be taken into account in determining obviousness”


Anderson’s-Black Rock v. Pavement Salvage (S. Ct. 1969)– Claims reciting a combination of known elements

must “produce a ‘new or different function’.”– A known combination of elements must interact

synergistically– Without invention, long felt need and commercial

success are not enough to demonstrate non-obviousness


Federal Circuit Court of Appeals (CAFC)– Sought more uniformity and consistency in

resolving § 103 obviousness issues – In re Fine (Fed. Cir. 1988)

TSM Test: Obviousness is only established where there is a teaching, suggestion, or motivation in prior art that would have led person of ordinary skill to combine or modify references


CAFC, Cont.– In re O’Farrell (Fed. Cir. 1988)

“Obvious to try” ≠ Obvious when– “Obvious to try" to vary all parameters or try each of

numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful

– Would have been "obvious to try" a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it


KSR invention:– Combination of known elements

old “adjustable” gas pedal with support member; and

pre-existing “electronic control” unit.

– KSR attached sensor to support member of fixed pivot pedal.

– Sensor stays fixed when pedal adjusted.

Adjustable pedal assembly

Electronic throttle control

KSR v. Teleflex (S. Ct. 2007)


District Court – Followed Graham framework

Compared prior art to claim– Applied TSM test– Summary Judgment of Invalidity

Combination of pedal elements was obvious


Federal Circuit Reversed– District Court failed to make “findings” as to specific

understanding/principle that would have motivated skilled worker to attach electric control to fixed support

– “Unless the prior art references address[ed] the precise problem patentee was trying to solve” the inventor would not have been motivated to look at those references


Supreme Court Reverses CAFC– CAFC’s application of TSM was too rigid

“No necessary inconsistency” between the TSM idea and Graham, but TSM cannot become a rigid rule that limits the obviousness inquiry

Flexible approach of prior Supreme Court cases inconsistent with CAFC application of TSM


Prior art disclosure of individual elements, without more, is insufficient for a finding that a combination of those elements is obvious– “… a patent composed of several elements is not

proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.”

– “… important to identify a reason that would have prompted a [PHOSITA] to combine the elements in the way the claimed new invention does.”


Was there a reason to combine known elements?– Must be “articulated reasoning” and “rational

underpinning” (quoting In re Kahn, (Fed. Cir. 2006)) Interrelated teachings of multiple patents Effects of demands known to the design community or

present in the marketplace Background knowledge possessed by a PHOSITA Hindsight with benefit of patentee’s disclosure is

impermissible


Even in the absence of TSM, an invention is obvious if “predictable”– “…a combination of familiar elements…is likely to

be obvious when it does no more than yield predictable results.”

– “…court must ask whether improvement is more than the predictable use of prior art elements according to their established functions.”

– “…structure already known in prior art…altered by the mere substitution of one element for another…combination must do more than yield a predictable result.”


“Obvious to try” = Obvious when– There is a design need or market pressure

to solve a problem and – Finite number of identified, predictable

solutions

Lessons from KSR

Combination patents are vulnerable– “[C]ombining prior art elements according to

their established function” is “predictable”

– Nonobviousness requires that a combination yield an unexpected (e.g., synergistic) result

Lessons from KSR

Obvious to Try– Prima facie obviousness based on

“obvious to try” may be overcome by demonstrating that the prior art Disclosed many possible solutions without

pointing to the claimed solution The claimed solution would have been

unpredictable based on the prior art

Obviousness at the USPTO

Post-KSR Examination Guidelines for Obviousness

(1) Combining prior art elements according to known methods to yield predictable results.

(2) Substitution of one known element for another to obtain predictable results.

(3) Applying known technique to known device (method or product) ready for improvement to yield predictable results.

(4) Obvious to Try – choosing from finite number of identified predictable solutions, with a reasonable expectation of success.

Obviousness at the USPTO

Post-KSR Examination Guidelines for Obviousness

(5) Known work in one field may promote variations in same or different field based on design incentives or market forces if variations would have been predictable to skilled artisan.

(6) Use of known techniques to improve similar devices (methods, or products) in same way (“results would have been predictable”).

(7) Some TSM in prior art that would have led skilled artisan to modify prior art reference or combine prior art reference teachings to arrive at claimed invention.

Syngenta Seeds v. Monsanto (Fed. Cir. 2007) (unpublished)

Syngenta patent:– Transgenic corn plant

producing an insecticidal protein (Bt) from bacteria

– Wild-type Bt gene has 40% GC content

– Corn genes have much higher GC content

– Syngenta claimed corn plants containing modified Bt gene with > 60% GC content

Syngenta Seeds v. Monsanto (Fed. Cir. 2007) (unpublished)

Prior art taught that:– Bt gene expression increased in tobacco plants

by increasing GC content– “[E]qually applicable in other plant species”

Federal Circuit affirmed obviousness

Aventis v. Lupin (Fed. Cir. 2007)

Patent– Aventis specifically

claimed the 5(S) stereoisomer of ramipril (an ACE inhibitor for treatment of high blood pressure) in a form substantially free of other isomers

Prior Art– Mixture of isomers

including the 5(S) stereoisomer

Aventis v. Lupin (Fed. Cir. 2007)

Federal Circuit finds obviousness– “Requiring an explicit teaching to purify the 5(S)

stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR.”

– Where “it is known that a desirable property of a mixture derives in whole or in part from a particular one of its components, or if the prior art would provide a person of ordinary skill in the art with reason to believe that this is so, the purified compound is prima facie obvious over the mixture even without an explicit teaching that the ingredient should be concentrated or purified.”

Takeda v. Alphapharm (Fed. Cir. 2007)

Takeda patent– Claimed pioglitazone -- a

thiazolidinedione (TZD) derivative used to treat diabetes

Prior art disclosed– A structurally related TZD

derivative– Weight gain associated w/

that TZD derivative

Takeda v. Alphapharm (Fed. Cir. 2007)

Federal Circuit Affirms Nonobviousness

– To establish prima facie obviousness of a chemical compound, must “identify some reason that would have led a chemist to modify a known compound in a particular manner.”

– Pioglitazone was not “obvious to try” because: Prior art disclosed broad selection of compounds any one of

which could have been selected as a lead compound AND Closest prior art compound exhibited negative properties that

would have directed PHOSITA away from pioglitazone (“teach away”)

In re Deuel (Fed. Cir. 1995)

Claims at issue

4. A purified and isolated DNA sequence consisting of a sequence encoding human heparin binding growth factor of 168 amino acids having the following amino acid sequence: Met Gln Ala ... [remainder of 168 amino acid sequence].

5. The purified and isolated cDNA of human heparin-binding growth factor having the following nucleotide sequence: GTCAAAGGCA ... [remainder of 961 nucleotide sequence].


Prior Art– Maniatis, Molecular Cloning: A Laboratory

Manual General methods for isolating cDNAs

– Bohlen Patent disclosing first 19 amino acids (out of 168 amino acids) of human heparin binding growth factor (HBGF)


Federal Circuit Upholds Validity of Claims

“The genetic code relationship between proteins and nucleic acids does not overcome the deficiencies of the cited references. A prior art disclosure of the amino acid sequence of a protein does not necessarily render particular DNA molecules encoding the protein obvious because the redundancy of the genetic code permits one to hypothesize an enormous number of DNA sequences coding for the protein. No particular one of these DNAs can be obvious unless there is something in the prior art to lead to the particular DNA and indicate that it should be prepared.”


“Thus, even if, as the examiner stated, the existence of general cloning techniques, coupled with knowledge of a protein's structure, might have provided motivation to prepare a cDNA or made it obvious to prepare a cDNA, that does not necessarily make obvious a particular claimed cDNA. "Obvious to try" has long been held not to constitute obviousness.” citing In re O'Farrell

Ex parte Kubin (B.P.A.I. 2007)

Patent– Claimed nucleic acid sequence encoding human NAIL, an

NK (natural killer) cell-surface marker– NAIL modulates the activity of NK cells (cytotoxic

lymphocytes) and thus plays a role in their immune response

Prior art disclosed– NAIL protein and a monoclonal antibody against NAIL– How to use the antibody to clone and sequence NAIL cDNA– Conventional methodologies of protein and DNA

sequencing– Cloned and sequenced mouse NAIL cDNA

Ex parte Kubin (B.P.A.I. 2007)

BPAI affirms obviousness– KSR’s “obvious to try” test applied because “[t]he ‘problem’

facing those in the art was to isolate NAIL cDNA, and there were a limited number of methodologies of doing so” PHOSITA would have reasonably expected one of the

conventional methodologies for cDNA isolation and sequencing to be successful

– Motivation to combine references “may be found in implicit factors, such as ‘knowledge of one of ordinary skill in the art, and [what] the nature of the problem to be solved as a whole would have suggested to those of ordinary skill in the art’” (quoting Alza v. Mylan (Fed. Cir. 2006)). PHOSITA would have been motivated to isolate human NAIL

cDNA based on the protein’s biological function

In re Kubin (Fed. Cir. 2009)

Federal Circuit affirms BPAI upholding invalidity of claims as obvious– Finds that the Supreme Court’s KSR decision

overturned In re Deuel and its admonition against an “obvious to try” test for obviousness

In re Kubin (Fed. Cir. 2009)

Rader Applies KSR to Unpredictable Arts“This court cannot deem irrelevant the ease and

predictability of cloning the gene that codes for that protein. This court cannot, in the face of KSR, cling to formalistic rules for obviousness, customize its legal tests for specific scientific fields in ways that deem entire classes of prior art teachings irrelevant, or discount the significant abilities of artisans of ordinary skill in an advanced area of art.”

Overcoming Obviousness Post-KSR

Overcoming prima facie obviousness will require– Demonstrable unpredictability of the art and claimed

invention– Unexpected/surprising results

Synergistic results New activity

– Prior art discloses numerous possible choices and/or only general guidance Best where prior art “teaches away” from claimed invention

– Failure to provide an “articulated reasoning” or “rational underpinning”

Scenario 1: Structural Similarity

Claim to compound A rejected as obvious over structurally similar prior art compound

How to overcome obviousness rejection – Compound A is unexpectedly potent compared to prior art compound– Compound A possesses an unexpected activity compared to prior art

compound Ex: Prior art compound is an anti-cancer drug, compound A shown to

(also) protect against Alzheimer’s disease– Prior art discloses a large number of compounds and provides no

guidance as to which should be chosen for further investigation– The prior art “teaches away” from compound A

Ex: Prior art compound possessed undesirable properties that would have led a PHOSITA away from similar compounds

– Synthesis/purification of compound A involved unexpected challenges or protocol had to be developed. Thus, no “reasonable expectation of success” in achieving compound A.

Scenario 2: Purification

Claim to compound A rejected as obvious over mixture containing compound A

How to overcome obviousness rejection – Not previously known that compound A is present in the prior art

mixture – Not previously known that compound A is the active ingredient in the

prior art mixture– Compound A is unexpectedly potent as compared to the prior art

mixture– Compound A possesses an unexpected property as compared to the

prior art mixture Prior art mixture is an anti-cancer drug, compound A shown to (also)

protect against Alzheimer’s disease– Synthesis / purification of compound A involved unexpected

challenges or protocol had to be developed

Scenario 3: Combination

Claim to composition comprising compound A + compound B rejected as obvious over compounds A and B individually disclosed by the prior art

How to overcome obviousness rejection– Composition comprising compound A and B has unexpected activity

not known for compound A and compound B– Compounds A and B act synergistically, not just additively, against

disease treated with compounds A and B separately– Prior art taught away from the combination of compounds A and B

(e.g., toxicity associated with individual compounds)– Prior art disclosed a large number of compounds and provided no

guidance as to which should be combined for further investigation– Combining compounds A and B was uniquely challenging or difficult

biotechnology novelty and nonobviousness 14 sep10

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