Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE PETER J. HUDSON, JOHN D. HALEY, HUGH D. NIALL AND JOHN SHINE
Appeal No. 90-1251
September 17, 1990
HEARD: July 24, 1990
Application for Patent filed February 14, 1983, Serial No. 466,191. Molecular Cloning and Characteristics of the Gene Sequence Coding for Procine Relaxin.
Susan J. Mack et al. for appellants
Supervisory Primary Examiner--Thomas G. Wiseman
Examiner--Jayme O. Huleatt
Before Goldstein, Lovell and Tarring
This appeal is from the examiner's final rejection of claims 1, 2, 4 to 11, 15, 16, 18 to 20, 30 and 32 to 34, which are all of the claims remaining in the application. Illustrative claims 1, 6 and 32 are reproduced below.
Claim 1. An isolated gene for the expression of porcine preprorelaxin.
6. An isolated gene for the separate expression of the signal, A, B or C peptide chains of porcine relaxin or any combination of two or more of the said chains.
Claim 32. An isolated gene, double-stranded DNA fragment, or DNA transfer vector as claimed [sic, in] Claims 1, 2, 4, 5, 6, 7, 8, 9, 10, 11 or 15 which has been modified by one or more of the procedures selected from the groups consisting of:
(a) deletion of one or more natural codons;
(b) addition of further codons to a natural sequence;
with the proviso that the thus modified gene, DNA sequence or transfer vector still encodes peptides with porcine relaxin activity.
References relied on by the examiner on appeal are:
Haley et al. (Haley), "Porcine Relaxin: Molecular Cloning and cDNA Structure," DNA, 1(2) 1982, pp. 155-162.
Hudson et al. (Hudson), "Molecular cloning and characterization of cDNA sequences coding for rat relaxin," Nature, 291(14), 1981, pp. 127-131.
Niall et al. (Niall), Annals New York Academy of Sciences, 380, 1982, pp. 13-21.
Schwabe et al. (Schwabe), "Primary Structure of the B-Chain of Porcine Relaxin," Biochemical and Biophysical Research Communications, 75(2), 1977, pp. 503-510.
James et al. (James), "Primary structure of porcine relaxin: homology with insulin and related growth factors," Nature, 267, 1977, pp. 544-546.
Tregear et al. (Tregear), "Porcine Relaxin: Synthesis and Structure Activity Relationships," Peptide: Synthesis, Structure, Function; Proc. American Peptide Symposium, 7th Ed. (Daniel et al., Ed.) 1981, pp. 249-252.
Itakura et al. (Itakura), "Chemical DNA Synthesis and Recombinant DNA Studies," Science, 209, 1980, pp. 1401-1405.
Khorana, "Total Synthesis of a Gene," Science, 203, 1979, pp. 614-625.
Isaacs, Relaxin and its structural relationship to insulin, Nature, 271, pp. 278-281 (1978).
Blundell et al. (Blundell), "Biology of relaxin and its role in the human," Proceedings of the 1st International Conference on Human Relaxin (Princeton, Excerpta Medica, 1983), pp. 14-21,
*2 Dodson et al. (Dodson), "Rat relaxin: insulin-like fold predicts a likely receptor binding region," Int. J. Biol. Macromol., 4, 1982, pp. 399- 405.
Claim 32 has been finally rejected under the first paragraph of 35 U.S.C. 112 as being based on an insufficiently enabling disclosure. We shall affirm this rejection.
We do not agree with the examiner's position that it is necessary for the specification to enable one "to determine all of the modified DNA sequences which would code for peptides with porcine relaxin activity" (answer on appeal, page 5, first full paragraph, emphasis supplied). We do, however, agree with the examiner's holding that "there is a lack of guidance in the specification directing one skilled in the art how to proceed in determining the appropriate ... modifications," with regard to practicing any embodiments within this claim (answer on appeal, page 7, first full paragraph). We agree substantially with the arguments set forth in the answer on appeal in support of this position, and we shall adopt it as our own, adding the following comments only to emphasize the reasons for our agreement with the examiner that the authorities cited by appellants are inadequate to support their position.
The two journal articles (Dodson and Isaacs) and the Conference Proceedings article (Blundell) relied on by appellants as support for the proposition that one of ordinary skill in the relevant art would not be put to undue experimentation in practicing the invention of claim 32 do not support that proposition and to a certain extent contradict it. The Isaacs article has to do with the structural relationship between relaxin and insulin. We find nothing either explicit or implicit in the article from which one would deduce that modification of the relaxin structure with retention of its activity would be readily predicted or practiced. Expression of relaxin activity in the relaxins of different species through a common receptor binding region, a phenomenon which might indicate that the non-common sequences could be relatively freely modified (but which would not unequivocally establish that fact) is a phenomenom "for which there is contradictory evidence," according to the disclosure of Blundell (top of page 20). The final paragraph of the Dodson article is similar in import.
All of the appealed claims have been finally rejected under 35 U.S.C. 102 as being anticipated by Haley. We shall not affirm this rejection.
The authorship of the Haley article overlaps considerably the inventive entity in the present application. There appears to be no controversy that the subject matter disclosed is substantially identical to, or at least that the article would anticipate, the present claims, if its effective date made it available as a reference under 35 U.S.C. 102(b). The weight of the evidence on the present record supports appellants' position that the article is unavailable as a reference.
*3 The publication date of the journal in which the Haley article appeared was two days before appellants' effective filing date under 35 U.S.C. 119. Appellants and the examiner appear to agree that the date the publication bears is inferentially the effective date under 35 U.S.C. 102 but that, if it is shown that the printed publication was not received by the public by the critical date, that inference may be rebutted. Compare Cannon, Inc. v. Plasser American Corp., 203 USPQ 440 (E.D.Va.1978), with Protein Foundation, Inc. v. Brenner, Comr. Pats., 151 USPQ 561 (D.D.C., 1966).
In the declaration of Susan Jovanovich, originally filed March 17, 1986 (Paper No. 15), and attached to the brief on appeal as Exhibit D, evidence is set forth that the journal in question was not mailed to subscribers until February 11, 1982, which is just one day prior to appellants' effective filing date. The examiner has not directed any specific comment to this particular evidence in the answer on appeal. Specifically, the examiner has not suggested how the journal could have been expected to be delivered on the same day it was mailed. Thus, we find that the weight of the evidence of record leads to a conclusion that the journal article in question was not available to the public prior to the critical date.
All the appealed claims have been finally rejected under 35 U.S.C. 103 as being unpatentable over Hudson or Niall taken together with any one of Schwabe, James and Tregear. We shall affirm this rejection.
Although we have carefully considered all of appellants' arguments, we find them to be unpersuasive of error on the part of the examiner. We consider the examiner's explanation of the initial conclusion of obviousness to be reasonable, and we find that all of appellants' arguments to the contrary have been convincingly rebutted in the answer on appeal. We shall, however, add the following comments for emphasis and completeness.
We agree with the examiner's conclusion that, once the amino acid sequence of a known useful protein is known, there is motivation for one of ordinary skill in the relevant art to construct a synthetic gene for biosynthesis of that protein. Whether or not the specific biosynthesis involved would have been obvious under 35 U.S.C. 103 depends on the specific facts in each case, but the critical inquiry is would there have been a reasonable expectation of success in achieving the desired goal, applying only the knowledge evidenced as being part of the prior art. In re O'Farrell, 853 F.2d 894, 7 USPQ2d 1673 (Fed.Cir.1988); Ex parte Erlich, 3 USPQ2d 1011 (BPAI 1986). The weight of the evidence of record here is that there would have been such a reasonable expectation of success.
*4 In addition to the fact that the amino acid sequences of the A and B chains of porcine relaxin were known (Schwabe, James and Tregear), the prior art evidence of record teaches that there was a preprorelaxin in rats, which contained, in addition to the A and B chain, a C chain which connected them (these three chains together constituting prorelaxin), and a signal peptide (the four chains together constituting preprorelaxin) (Hudson and Niall). It was also at least suggested that porcine relaxin would have a similar precursor: see the first paragraph of the Niall article and the second and third paragraphs of the Hudson article. Thus appellants' argument that one of ordinary skill in the relevant art would not have expected the existence of a preprorelaxin in the pig is not persuasive.
Quite apart from the foregoing discussion, the examiner's rejection appears to be based as well on the proposition that one following the procedures of Niall and Hudson would have discovered the existence of, and would have arrived at the proper structure for, porcine preprorelaxin in the same manner that Niall and Hudson did with regard to rat preprorelaxin. This proposition is not rebutted by appellants' arguments concerning the redundancy of the genetic code since the references themselves discuss this complicating factor and present methods to deal with it, as the examiner has indicated in the answer on appeal.
To summarize, from the record before us, it does not appear that appellants have had to resort to any significantly different biosynthetic techniques than those set forth by Hudson and Niall with regard to rat relaxin, prorelaxin and preprorelaxin to arrive at the claimed subject matter relating to porcine relaxin, prorelaxin and preprorelaxin and that the existence and at least partial structural identity of these various porcine relaxins was either explicitly set forth or strongly suggested in the prior art, so that the claimed subject matter would have been obvious under 35 U.S.C. 103.
Claims 6, 8, 9, 11, 16, 32 and 34 have been finally rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Itakura or Khorhana taken with any one of Schwabe, James and Tregear. We shall affirm this rejection.
In the brief on appeal, appellants have not directed their arguments against obviousness separately to the two separate rejections. The argument for patentability based on the assertedly unpredictable existence of a preprorelaxin, i.e., the composite of the signal, A, B and C chains, appears to have been recognized by the examiner as being particularly relevant to this rejection. Accordingly, the rejection has been limited to the claims enumerated, which require only the preparation of a gene for the A and/or B peptide chain.
The techniques disclosed by Khorhana and Itakura appear to involve the total chemical synthesis of genes of interest unlike the techniques disclosed by Hudson and Niall, which utilize synthesized probes and naturally occurring RNA, which latter process is also disclosed as being used in appellants' specification. Although the total synthesis is clearly a time consuming procedure, we agree with the examiner's conclusion that, in view of the specific reference teachings of record, including the known nature of the amino acid sequence of porcine relaxin, the A and B chains of which are not particularly long, carrying out the arduous synthetic processes disclosed by Khorhana and Itakura to produce the required polynucleotides would have required only experimentation within ordinary skill in the art.
*5 The decision of the examiner is affirmed.
No time period for taking any subsequent action in connection with this appeal may be extended under 37 CFR 1.136(a). See the final rule notice, 54 F.R. 29548 (July 13, 1989), 1105 O.G. 5 (August 1, 1989).
BOARD OF PATENT APPEALS AND INTERFERENCES
Charles N. Lovell
Henry W. Tarring, II