Ex parte Kubin: Obviousness at the USPTO in biotechnology
As mentioned previously, the BPAI designated an opinion as precedential today addressing the issues of obviousness, enablement, and the written description requirement in the context of biotechnology inventions. These issues were addressed in the context of patenting a gene involved in regulating the immune system.
Addressing the obviousness issue, the board determined that the previous knowledge of the protein sequence in other species combined with the limited number of approaches to isolate the gene rendered the invention obvious under the "obvious to try" standard. Citing to KSR, the Board determined that the results obtained were merely the product of ordinary skill and common sense and affirmed the rejection of the examiner.
The enablement and written description issues stemmed from the claim of sequences with at least 80% identity to the isolated sequence. The enablement rejection was reversed because while extensive experimentation may be required, the experimentation would have been routine, not undue. However, the board upheld the written description rejection on the grounds that the two exemplary sequences provided in the specification were not sufficiently different to demonstrate possession of the entire genus claimed (all sequences with 80% similarity).
More detail of Ex parte Kubin after the jump.
This case was the result of an attempt to patent a gene that encodes the NK (natural killer) Cell Activation Inducing Ligand ("NAIL") protein. This protein is displayed on the surface of cells and helps to regulate the activity of the T-cells of a person's immune system. Claim 73 of the application is representative (the claims were not argued separately):
73. An isolated nucleic acid molecule comprising a polynucleotide encoding a polypeptide at least 80% identical to amino acids 22-221 of SEQ ID NO:2, wherein the polypeptide binds CD48.
The claims were rejected as obvious under § 103(a) and not enabled or adequately described under § 112.
Obviousness
The claims were rejected as obvious based on a combination of three pieces of prior art, namely, the Valiante reference (a patent for the analogous protein in mice, called p38), the Sambrook reference (a book that teaches standard gene cloning/isolation techniques), and the Matthew reference (a scientific article that demonstrated that the NAIL gene was present, but was not actually expressed in humans). The Board framed the obviousness issue as:
Would Appellants' claimed nucleotide sequence have been obvious to one of ordinary skill in the art, based on Valiante's disclosure of p38 and his express teachings how to isolate its cDNA by conventional techniques?
In addressing the issue of obviousness the board focused on whether the patenting of the protein in mice (with accompanying descriptions of how to isolate the gene) rendered subsequent attempts to isolate the same gene, using standard techniques, in humans obvious. The applicant first claimed that the references did not provide adequate written description of the claimed sequences. The board rejected this argument, noting that the references need only adequately describe a single member of the claimed genus to be relevant for obviousness, as "a single obvious species within a claimed genus renders the claimed genus unpatentable under § 103."
Turning to the merits of the obviousness rejection, the Board stated that "[u]nder KSR, it's now apparent 'obvious to try' may be an appropriate test in more situations than we previously contemplated." Noting that the applicants relied heavily on the Federal Circuit's Deuel decision, the Board apparently believes that the viability of Deuel may be doubtful post-KSR to the extent it rejects the "obvious to try" standard. Quoting KSR, the Board then held 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. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."
This reasoning is applicable here. The "problem" facing those in the art was to isolate NAIL cDNA, and there were a limited number of methodologies available to do so. The skilled artisan would have had reason to try these methodologies with the reasonable expectation that at least one would be successful. Thus, isolating NAIL cDNA was "the product not of innovation but of ordinary skill and common sense," leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.
The Board also rejected the applicants' argument that the references taught away from the invention (based on Matthews' statement that the relevant gene was not expressed in humans). Specifically, the Board noted that Matthews was important not for its statements regarding expression in humans, but rather that "the cDNA encoding 2B4, the mouse version of Valiante's p38 expressed on all NK cells, can be isolated and sequenced. Thus, the teachings of Mathews, when considered as a whole, support the Examiner's § 103 ground of rejection." As a result, the obviousness rejection was affirmed.
The Board framed the enablement issue as:
Considering the relevant Wands factors, including the prior art teachings cited by the Examiner and Appellants to establish the level of predictability in the relevant art, would undue experimentation have been required to practice the full scope of claim 73?
The application claimed the genus of all sequences with 80% similarity to the identified sequence that maintained functionality. This approach is common in molecular biology applications as minor changes in gene sequences can still have the same function as the unaltered sequence. The Board noted that the application disclosed methods for making the changes and testing the functionality of the resulting modified proteins. The Board further noted that the amount of experimentation required to practice the full scope of the invention was considerable, however, such experimentation was routine in the art. As a result, the experimentation, while extensive, was not "undue," and the Board reversed the enablement rejection.
Written description
The Board framed the written description issue as:
Does Appellants' Specification contain a written description sufficient to show they had possession of the full scope of their claimed invention at the time the application was filed, as required by Federal Circuit precedent?
First, the Board noted that, despite considerable overlap with the enablement requirement, the enablement and written description requirements were distinct and required a separate inquiry. The Board then turned to the two example sequences provided in the application. Noting that the disclosed sequences did not vary amino acid positions 22-221 of the resultant protein as claimed, the board concluded that these examples were not sufficiently representative of the genus of sequences with 80% similarity to the isolated sequence while retaining functionality of the original gene. While the application did disclose how to make and test the other sequences in the genus, the Board stated that "[p]ossession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features." Based on this reasoning from the Eli Lilly line of precedent, the Board upheld the rejection for lack of written description.
In summary, this case indicates an increase in use of the "obvious to try" standard after KSR, and that it will likely become more difficult to overcome obviousness rejections in more than just the mechanical arts post-KSR. Based on the Board's reasoning, rejections appear likely stating that inventions are just applying one of a finite number of known methods to achieve a predictable result. It also demonstrates that patenting gene sequences with a percent similarity to an identified sequence can be allowable, provided that the application provides several sequence variants to represent the genus claimed and discloses methods to create and test the variant sequences.
To read the full decision in Ex parte Kubin, click here.
Patently-O reports on the case here.
The PLI patent blog expresses doubts about the Board's characterization of the vitality of Deuel here.