Bell, In re

• Citation: 991 F.2d 781,26 USPQ2d 1529
• Decision Date: 20 April 1993
• Docket Number: No. 92-1375,92-1375
• Parties: , 26 U.S.P.Q.2d 1529 In re Graeme I. BELL, Leslie B. Rall and James P. Merryweather.
• Court: United States Courts of Appeals. United States Court of Appeals for the Federal Circuit

Page 781

991 F.2d 781

61 USLW 2692, 26 U.S.P.Q.2d 1529

In re Graeme I. BELL, Leslie B. Rall and James P. Merryweather.

No. 92-1375.

United States Court of Appeals,

Federal Circuit.

April 20, 1993.

Robert P. Blackburn, Chiron Corp., Emeryville, CA, argued for appellant. With him on the brief were Debra A. Shetka and Thomas E. Ciotti, Morrison & Foerster, Palo Alto, CA, and Donald S. Chisum, Morrison & Foerster, Seattle, WA.

Teddy S. Gron, Associate Sol., Office of the Sol., Arlington, VA, argued for appellee. With him on the brief was Fred E. McKelvey, Sol. Of counsel were John W. Dewhirst, Lee E. Barrett, Richard E. Schafer and Albin F. Drost.

Before RICH, LOURIE, and SCHALL, Circuit Judges.

LOURIE, Circuit Judge.

Applicants Graeme I. Bell, Leslie B. Rall, and James P. Merryweather (Bell) appeal from the March 10, 1992 decision of the U.S. Patent and Trademark Office (PTO) Board of Patent Appeals and Interferences, Appeal No. 91-1124, affirming the examiner's final rejection of claims 25-46 of application Serial No. 065,673, entitled "Preproinsulin-Like Growth Factors I and II," as unpatentable on the ground of obviousness under 35 U.S.C. § 103 (1988). Because the Board erred in concluding that the claimed nucleic acid molecules would have been obvious in light of the cited prior art, we reverse.

BACKGROUND

The claims of the application at issue are directed to nucleic acid molecules (DNA and RNA) ¹ containing human sequences ² which code for human insulin-like growth factors I and II(IGF), single chain serum proteins that play a role in the mediation of somatic cell growth following the administration of growth hormones. ³

The relevant prior art consists of two publications by Rinderknecht ⁴ disclosing amino acid sequences for IGF-I and -II and U.S. Patent 4,394,443 to Weissman et al., entitled "Method for Cloning Genes." Weissman describes a general method for isolating a gene for which at least a short amino acid sequence of the encoded protein is known. The method involves preparing a nucleotide probe corresponding to the known amino acid sequence and using that probe to isolate the gene of interest. It teaches that it is advantageous to design a probe based on amino acids specified by unique codons. ⁵ The Weissman patent specifically describes the isolation of a gene which codes for human histocompatibility antigen, a protein unrelated to IGF. It describes the design of the probe employed, stating that it was based on amino acids specified by unique codons.

The examiner rejected the claims as obvious over the combined teachings of Rinderknecht and Weissman. She determined that it would have been obvious, "albeit tedious," from the teachings of Weissman to prepare probes based on the Rinderknecht amino acid sequences to obtain the claimed nucleic acid molecules. According to the examiner, "it is clear from [Weissman] that the ordinary artisan knows how to find the nucleic acid when the amino acid sequence is known" and that "the claimed sequences and hosts would have been readily determinable by and obvious to those of ordinary skill in the art at the time the invention was made."

The Board affirmed the examiner's rejection, holding that the examiner had established a prima facie case of obviousness for the claimed sequences "despite the lack of conventional indicia of obviousness, e.g., structural similarity between the DNA which codes for IGF-I and the amino acid sequence of the polypeptide which constitues [sic] IGF-I." Slip op. at 6. The Board reasoned that "although a protein and its DNA are not structurally similar, they are correspondently linked via the genetic code." Id. at 4 n. 1. In view of Weissman, the Board concluded that there was no evidence "that one skilled in the art, knowing the amino acid sequences of the desired proteins, would not have been able to predictably clone the desired DNA sequences without undue experimentation." Id. at 8.

The issue before us is whether the Board correctly determined that the amino acid sequence of a protein in conjunction with a reference indicating a general method of cloning renders the gene prima facie obvious.

DISCUSSION

We review an obviousness determination by the Board de novo. In re Vaeck, 947 F.2d 488, 493, 20 USPQ2d 1438, 1442 (Fed.Cir.1991). Bell argues that the PTO has not shown how the prior art references, either alone or in combination, teach or suggest the claimed invention, and thus that it has failed to establish a prima facie case of obviousness.

We agree. The PTO bears the burden of establishing a case of prima facie obviousness. In re Fine, 837 F.2d 1071, 1074, 5 USPQ2d 1596, 1598 (Fed.Cir.1988). "A prima facie case of obviousness is established when the teachings from the prior art itself would appear to have suggested the claimed subject matter to a person of ordinary skill in the art." In re Rinehart, 531 F.2d 1048, 1051, 189 USPQ 143, 147 (CCPA 1976).

The Board supported the examiner's view that the "correspondent link" between We do not accept this proposition. It may be true that, knowing the structure of the protein, one can use the genetic code to hypothesize possible structures for the corresponding gene and that one thus has the potential for obtaining that gene. However, because of the degeneracy of the genetic code, there are a vast number of nucleotide sequences that might code for a specific protein. In the case of IGF, Bell has argued without contradiction that the Rinderknecht amino acid sequences could be coded for by more than 10 ³⁶ different nucleotide sequences, only a few of which are the human sequences that Bell now claims. Therefore, given the nearly infinite number of possibilities suggested by the prior art, and the failure of the cited prior art to suggest which of those possibilities is the human sequence, the claimed sequences would not have been obvious.

                a gene and its encoded protein via the genetic code renders the gene obvious when the amino acid sequence is known.   In effect, this amounts to a rejection based on the Rinderknecht references alone.   Implicit in that conclusion is the proposition that, just as closely related homologs, analogs, and isomers in chemistry may create a prima facie case, see In re Dillon, 919 F.2d 688, 696, 16 USPQ2d 1897, 1904 (Fed.Cir.1990) (in banc ), cert. denied, --- U.S. ----, 111 S.Ct. 1682, 114 L.Ed.2d 77 (1991), the established relationship in the genetic code between a nucleic acid and the protein it encodes also makes a gene prima facie obvious over its correspondent protein
                

Bell does not claim all of the 10 ³⁶ nucleic acids that might potentially code for IGF. Neither does Bell claim all nucleic acids coding for a protein having the biological activity of IGF. Rather, Bell claims only the human nucleic acid sequences coding for IGF. Absent anything in the cited prior art suggesting which of the 10 ³⁶ possible sequences suggested by Rinderknecht corresponds to the IGF gene, the PTO has not met its burden of establishing that the prior art would have suggested the claimed sequences.

This is not to say that a gene is never rendered obvious when the amino acid sequence of its coded protein is known. Bell concedes that in a case in which a known amino acid sequence is specified exclusively by unique codons, the gene might have been obvious. Such a case is not before us. ⁶ Here, where Rinderknecht suggests a vast number of possible nucleic acid sequences, we conclude that the claimed human sequences would not have been obvious.

Combining Rinderknecht with Weissman does not fill the gap. Obviousness " 'cannot be established by combining the teachings of the prior art to produce the claimed...