Patent Docs: DNA Non-obviousness under Ex parte Kubin (It Gets Worse) - Sent Using Google Toolbar

Patent Docs: DNA Non-obviousness under Ex parte Kubin (It Gets Worse)

DNA Non-obviousness under Ex parte Kubin (It Gets Worse)

    By Kevin E. Noonan --

Uspto_seal Last week, the U.S. Patent and Trademark Office promulgated its long-awaited guidelines for Examiners in making obviousness determinations in view of the U.S. Supreme Court's decision in KSR Int'l Co. v. Teleflex Inc. (see "Patent Office Issues Examination Guidelines Regarding Obviousness after KSR").

As part of these guidelines, the Office provided various rationales available to Examiners to fulfill KSR's requirement that the factfinder provide a reasoned basis for an obviousness determination.  One such rationale dealt with the "obvious to try" issue, as discussed by the Supreme Court in KSR:

When there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.

The guidelines with regard to the "obvious to try" standard are set forth in Rationale E:

(E) ''Obvious to try'' - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;

(1) a finding that at the time of the invention, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem;

(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;

(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success; and

(4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness.

Citing KSR, the Notice requires for this rationale that an Examiner articulate facts supporting the conclusion that ''a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."

The issue for biotechnology arises in Example 3 illustrating how an Examiner should apply this rationale; that Examiner relates to the Board's decision in Ex parte Kubin (see Patent Docs post on this case):

Example 3:  The claimed invention in Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), was an isolated nucleic acid molecule.  The claim stated that the nucleic acid encoded a particular polypeptide.  The encoded polypeptide was identified in the claim by its partially specified sequence, and by its ability to bind to a specified protein.

A prior art patent to Valiante taught the polypeptide encoded by the claimed nucleic acid, but did not disclose either the sequence of the polypeptide, or the claimed isolated nucleic acid molecule.  However, Valiante did disclose that by employing conventional methods, such as those disclosed by a prior art laboratory manual by Sambrook, the sequence of the polypeptide could be determined, and the nucleic acid molecule could be isolated.  In view of Valiante's  disclosure of the polypeptide, and of routine prior art methods for sequencing the polypeptide and isolating the nucleic acid molecule, the Board found that a person of ordinary skill in the art would have had a reasonable expectation that a nucleic acid molecule within the claimed scope could have been successfully obtained.

Relying on In re Deuel, Appellant argued that it was improper for the Office to use the polypeptide of the Valiante patent together with the methods described in Sambrook to reject a claim drawn to a specific nucleic acid molecule without providing a reference showing or suggesting a structurally similar nucleic acid molecule.  Citing KSR, the Board stated that ''when there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.''  The Board noted that the problem facing those in the art was to isolate a specific nucleic acid, and there were a limited number of methods available to do so.  The Board concluded that the skilled artisan would have had reason to try these methods with the reasonable expectation that at least one would be successful.  Thus, isolating the specific nucleic acid molecule claimed was ''the product not of innovation but of ordinary skill and common sense.''

This is nothing more, and nothing less, than a per se obviousness standard.  According to the guidelines, the existence of an isolated polypeptide in the prior art, without more, renders obvious a claim to a nucleic acid encoding the polypeptide.  Note that the guidelines do not require that even a partial amino acid sequence of the prior art polypeptide be known, nor does it require that a cell or tissue source of the protein be known, to raise a prima facie obviousness determination against a nucleic acid claim.  To put Factorviiibig_2 this in context, human blood clotting Factor VIII, which causes Hemophilia A, was "isolated" from fractionated blood components many years before the gene encoding the protein was isolated.  During that time, the cells producing the protein were not known; it has since been found to be produced by vascular endothelial cells.  Despite this inherent uncertainty, according to the Patent Office (no doubt having been "constantly advised by the patent examiners, who are highly skilled in this art, that cloning procedures are routine in the art"), the nucleic acid encoding Factor VIII would be prima facie obvious in view of the mere existence of a purified preparation of the protein in the art.  This rationale goes even further than the Board in Deuel, since there, the Board's obviousness decision was based on "the examiners urg[ing] that when the sequence of a protein is placed into the public domain, the gene is also placed into the public domain because of the routine nature of cloning techniques."  Here, even this requirement has been dropped.

This result is not required by KSR, and is in fact contrary to it.  The Court did not abrogate In re Deuel in the KSR decision, and the portion of KSR dealing with the "obvious to try" standard is consistent with Federal Circuit precedent, including Deuel:

It is true that this court and its predecessors have repeatedly emphasized that "obvious to try" is not the standard under §103.  However, the meaning of this maxim is sometimes lost.  Any invention that would in fact have been obvious under §103 would also have been, in a sense, obvious to try.  The question is: when is an invention that was obvious to try nevertheless nonobvious?

The admonition that "obvious to try" is not the standard under § 103 has been directed mainly at two kinds of error.  In some cases, what would have been "obvious to try" would have been 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.  In others, what was "obvious to try" was to explore 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.

Obviousness does not require absolute predictability of success.  Indeed, for many inventions that seem quite obvious, there is no absolute predictability of success until the invention is reduced to practice.  There is always at least a possibility of unexpected results, that would then provide an objective basis for showing that the invention, although apparently obvious, was in law nonobvious.  For obviousness under § 103, all that is required is a reasonable expectation of success.

In re O'Farrell (Fed. Cir. 1988) (citations omitted).  Neither of these situations apply per se to isolating a nucleic acid that encodes a known protein.

The guidelines are not even consistent with the Board's decision in Kubin.  There, the Board cited several factual distinctions between the obviousness issue presented by Kubin and the facts in Deuel, including:

1.  In Kubin, a cell "unambiguously" (see below) expressing the gene was known; in Deuel, a protein that the prior art taught was expressed in brain was cloned from placenta.

2.  In Kubin, the nucleotide and amino acid sequence of the mouse ortholog of human NAIL was known; in Deuel, the prior art disclosed three different brain-specific proteins and a partial amino-terminal amino acid sequence thereof.

3.  In Kubin, the art provided an isolated preparation of the cognate protein and a monoclonal antibody that binds to the protein; in Deuel, the art disclosed isolated preparations of three different brain-specific proteins but no antibodies.

4.  In Kubin, the art provided a monoclonal antibody specific for the gene product of the desired cDNA and thus providing a specific probe; in Deuel, the probes were a plurality of degenerate oligonucleotides prepared from the partial amino-terminal amino acid sequences.

5.  In Kubin, the art has developed expression cloning technology and provided an antibody probe specific for the gene product of the desired clone; in Deuel, the absence of a specific antibody precluded use of expression cloning technology.

None of these factual issues are mentioned or required to be considered under the guidelines.

On the law, the Board conflated (and the guidelines set in stone) the issues of the obviousness of a composition of matter and the obviousness of producing it.  This is the same mistake that the Board made in Deuel :

The PTO's focus on known methods for potentially isolating the claimed DNA molecules is also misplaced because the claims at issue define compounds, not methods.  See In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993).  In Bell, the PTO asserted a rejection based upon the combination of a primary reference disclosing a protein (and its complete amino acid sequence) with a secondary reference describing a general method of gene cloning.  We reversed the rejection, holding in part that "the PTO's focus on Bell's method is misplaced.  Bell does not claim a method.  Bell claims compositions, and the issue is the obviousness of the claimed compositions, not of the method by which they are made."  Id.

We today reaffirm the principle, stated in Bell, that the existence of a general method of isolating cDNA or DNA molecules is essentially irrelevant to the question whether the specific molecules themselves would have been obvious, in the absence of other prior art that suggests the claimed DNAs.  . . .  There must, however, still be prior art that suggests the claimed compound in order for a prima facie case of obviousness to be made out; as we have already indicated, that prior art was lacking here with respect to claims 5 and 7.  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.  In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1680-81 (Fed. Cir. 1988).  A general incentive does not make obvious a particular result, nor does the existence of techniques by which those efforts can be carried out.  Thus, Maniatis's teachings, even in combination with Bohlen, fail to suggest the claimed invention.

The differences in the underlying technological sophistication in the art noted by the Board in Kubin could, under the appropriate circumstances,  render obvious a nucleic acid encoding, for example, a highly-conserved sequence where the art disclosed closely-related species orthologs, the cell or tissue of  origin was reliably known, and specific reagents, such as monoclonal antibodies to the protein, were readily available.  None of these factors are required under the Office's KSR rationale to permit an Examiner to assert a prima facie case of obviousness against a nucleic acid claim.  Perhaps the Office is merely reflecting the current trend to pass as much of the examination burden as possible onto applicants, and expects that in instances where there are facts contrary to Kubin or the guidelines, applicants will provide sufficient rebuttal evidence to overcome the prima facie case.  This procedural avenue, however, does not address the analytical mistake of equating obviousness of the method of making with the obviousness of the thing made.  And by promulgating a per se rule of obviousness it is the Office, not the Federal Circuit, that runs directly afoul of Supreme Court precedent.

Unless Kubin has filed an appeal with a district court or the Federal Circuit, the only way that this guideline will be overturned will be after it has been improperly applied, appealed, affirmed by the Board, and then sent to the Federal Circuit for review.  Even then, the facts of that case will need to be sufficient for the CAFC to properly consider the issue.  It would be easier, and better for American innovation (in biotechnology, where the U.S. remains a leader) if the Office would be more preoccupied with allowing than rejecting patents.  On recent evidence, at least with regard to nucleic acid claiming, the Patent Office appears more interested in settling scores with the Federal Circuit.

Posted at 10:52 PM in Commentary, Patent