Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE ALVIN S. STERN
Appeal No. 86-2919
March 24, 1989
Application for Patent filed September 24, 1984, Serial No. 653,165. This application is a Division of Serial No. 418,927, filed September 16, 1982, now U.S. Patent No. 4,490,290, granted December 25, 1984. Homogeneous Human Interleukin 2.
George M. Gould et al. for appellant
Primary Examiner--Morton Foelak
UPON REQUEST FOR RECONSIDERATION
Appellant requests reconsideration of our decision mailed November 20, 1987, in which we affirmed the examiner's rejection of the appealed claims under 35 U.S.C. 103 as unpatentable over any of Gillis, Frabricius, Welte, Mochizuki, Stadler or either of the two Mier references in view of Pestka. [FN2] Appellant contends that the rationale underpinning our affirmance of the examiner's rejection differed from the rationale employed by the examiner to such an extent that it amounted to a new ground of rejection under 37 CFR 1.196(b). We agree for the reasons expressed by appellant in the Request for Reconsideration.
We hereby designate our affirmance of the examiner's rejection under 35 U.S.C. 103 as a new ground of rejection pursuant to the provisions of 37 CFR 1.196(b) so that appellant may be afforded the procedural safeguards of that rule which include the option of submitting additional evidence and have the new rejection considered by the examiner or having the new rejection reconsidered by the Board of Patent Appeals and Interferences on the existing record. Inasmuch as appellant has submitted new objective evidence in the form of a declaration, we construe appellant's response as an election to proceed before the examiner. Accordingly, this case is forwarded to the examiner.
BOARD OF PATENT APPEALS AND INTERFERENCES
Arthur J. Steiner
William F. Smith
FN1. Milestone, Examiner-in-Chief, retired subsequent to the decision and, therefore, could not participate in responding to this Request for Reconsideration.
Arthur J. Steiner
This is an appeal from the final rejection of claim 1, which is the only claim remaining in the application.
Claim 1 reads as follows:
2. Human interleukin 2 as a homogeneous protein characterized in having a specific activity of about 1.4 x 109 U/mg, a pI of about 5.68 and a composite amino acid composition as follows:
and a partial internal peptide sequence as follows: -Ile-Leu-Asn-Gly-Ile-Asn-Asn-Tyr-Lys-Asn-Pro-Lys-Leu-Thr-.
The references relied upon by the examiner are:
Pestka et al. (Pestka) 4,289,690 Sept. 15, 1981
Frabricius et al. (Frabricius) 4,390,623 June 28, 1983
Gillis et al. (Gillis). "Biochemical Characterization of Lymphocyte Regulatory Molecules. II. Purification of a Class of Rat and Human Lymphokines." The Journal of Immunology. Vol. 124, No. 4., Apr. 1980, pp. 1954-1962.
Welte et al. (Welte). "Purification of Human Interleukin 2 to Apparent Homogeneity and its Molecular Heterogeneity." The Journal of Experimental Medicine, Vol. 156, No. 2, Aug. 1, 1982, pp. 454-464.
Stadler et al. (Stadler). "Monoclonal Antibody Against Human Interleukin 2 (IL 2). I. Purification of IL 2 for the Production of Monoclonal Antibodies." The Journal of Immunology. Vol. 128, No. 4, Apr., 1982, pp. 1620-1624.
Mier et al. (Mier I). "The Purification and Properties of Human T Cell Growth Factor." The Journal of Immunology. Vol. 128, No. 3, March 1982, pp. 1122- 1127.
Mier et al. (Mier II). "Purification and Some Characteristics of Humen T-cell Growth Factor From Phytohemagglutinin-Simulated Lymphocyte-Conditioned Media." Proc. Natl. Acad. Sci. USA, Vol. 77, No. 10, Oct. 1980, pp. 6134-6138.
Claim 1 stands rejected under 35 U.S.C. 102 as anticipated by or, alternatively, under 35 U.S.C. 103 as unpatentable over each of Gillis and Frabricius. Claim 1 also stands rejected under 35 U.S.C. 103 as unpatentable over any of Gillis, Frabricius, Welt, Mochizuki, Stadler or either of the Mier references considered alone or in view of Pestka.
Upon consideration of the entire record and of the arguments advanced on appeal, the examiner's rejection of claim 1 under 35 U.S.C. 102 as anticipated by each of Gillis and Frabricius is reversed; the rejection of claim 1 under 35 U.S.C. 103 as unpatentable over any of Gillis, Frabricius, Welte, Mochizuki, Stadler or either of the Mier references is reversed; however, the rejection of claim 1 under 35 U.S.C. 103 as unpatentable over any of Gillis, Frabricius, Welte, Mochizuki, Stadler or either of the Mier references in view of Pestka is affirmed.
The claimed invention is directed to human interleukin 2 (IL-2) which has been purified to homogeneity. IL-2 is a lymphokine which is produced in minute amounts by appropriate stimulation of lymphocytes along with numerous cogenerated lymphokines. Because of its known biological activity, those skilled in this particular art have made various apparently unsuccessful attempts to purify IL-2 to homogeneity; i.e., to purify IL-2 to the extent of isolating it from cogenerated lymphokines. Appellant has achieved this art-recognized objective by means of a novel process for which he has been awarded patent protection. [FN1] In this application, appellant claims IL-2 purified to homogeneity and defined in terms of heretofore unascertained properties which include specific activity and amino acid composition data.
*3 In rejecting the appealed claims under 35 U.S.C. 102, the examiner relies upon each of Frabricius and Gillis. Frabricius discloses an unpurified mixture containing IL-2 and coproduced proteins. The disclosed concentration step is performed to merely remove matter such as salt, sugar and water. Gillis discloses a method of purifying IL-2 which is said to result in an "apparently homogeneous" composition containing IL-2. The Stern declaration of October 24, 1983, which is supported by subsequent declarations, reports that Gillis' sample contains substantially less than 1% of human IL-2, which evidence is corroborated by Gillis' own declaration.
It would, therefore, appear that neither Frabricius nor Gillis discloses human IL-2 in homogeneous form. This difference between the claimed invention and the applied prior art is apparently recognized by the examiner; however, the examiner, for some reason which is not entirely clear from the Answer, continues to maintain a rejection under 35 U.S.C. 102.
On page 5 of the Answer, the examiner advances the theory that:
"... the degree of purity alone is not sufficient to warrant a patentably distinct protein, and the burden is upon applicant to show such."
We are not familiar with any jurisprudential precedent which supports the examiner's sweeping statement. We agree with appellant's position with respect to the applicability of the decisions cited by the examiner and appellant.
It is clear from the record and appreciated by the examiner that IL-2 is known to enjoy biological activity in the treatment of patients afflicted with tumors. Conventional methods of obtaining IL-2 result in a "soup" containing IL-2 in minute quantities together with various cogenerated proteins. Skilled workers in this particular art have sought to purify IL-2 to homogeneity and apparently have not succeeded. Against this background, the examiner's cavalier disposition of the degree of purity expressed in the appealed claim is completely unrealistic and clearly erroneous. Cf. In re Kratz, 592 F.2d 1169, 201 USPQ 71 (CCPA 1979); In re Bergstrom, 166 F.2d 1394, 166 USPQ 256 (CCPA 1970); In re Cofer, 354 F.2d 664, 148 USPQ 268 (CCPA 1966). We venture to say that the philosophy unpinning the examiner's rejection would, in effect, stifle rather than
"... promote the progress of science and useful arts ..." (ART. 1, SEC. 8, CL. 8, of the Constitution).
Cf. also Diamond v. Chakrabarty, 206 USPQ 193 (CCPA 1980); In re Bergy, 596 F.2d 952, 201 USPQ 352 (CCPA 1979).
Accordingly, the examiner's rejection of the appealed claims under 35 U.S.C. 102 as anticipated by each of Frabricius and Gillis is reversed.
*4 The examiner has also rejected claim 1 under 35 U.S.C. 103 as unpatentable over Frabricius, Gillis or a plurality of additional references. Of the additional references relied upon, Welte appears to be the most pertinent since IL-2 is reported to have been purified to "apparent homogeneity." However, as recognized by the examiner, the degree of purification achieved by Welte is markedly less than the degree of purification achieved by appellant. This is supported by the Stern declaration of October 24, 1983. The examiner has failed to articulate any recognizable theory to support the rejection of the appealed claim under 35 U.S.C. 103 as unpatentable over any of these references. Simply put, the closest prior art references, i.e., Gillis and Welte, according to appellant's uncontroverted evidence, achieve a degree of purification which is substantially less than two orders of magnitude than the degree of purification set forth in the appealed claim. Recognizing this difference, the examiner states on page 4 of the Answer that
"Although the prior art fails to recite a protein having such a high specific activity, such is deemed obvious relative to advances in technology that evolves [sic, evolve] more sophisticated purification processes that produces [sic, produce] such high degree of purity." (Emphasis supplied).
The examiner should be aware that "deeming" does not discharge him from the burden of providing the requisite factual basis and establishing the requisite motivation to support a conclusion of obviousness. Cf. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed.Cir.1985). The examiner's reference to unidentified phantom prior art techniques falls far short of the mark. In re Warner, 379 F.2d 10111, 154 USPQ 173 (CCPA 1967); In re Freed, 425 F.2d 785, 165 USPQ 570 (CCPA 1970); In re Cofer, supra. Accordingly, the examiner's rejection of the appealed claims under 35 U.S.C. 103 as unpatentable over any of the primary references, considered singly, is reversed.
As discussed above, there is a recognition in the art of the desirability of purifying IL-2 to homogeneity. Pestka discloses a process employing high performance liquid chromatography capable of purifying to homogeneity proteins exhibiting molecular weights in excess of 12,000. Such a protein is IL-2. Although Pestka focuses upon the purification of interferon and does not specifically identify IL-2, it is unmistakenly revealed that the disclosed high performance liquid chromatographic process is capable of purifying proteins other than interferon. See, for example, column 3 of Pestka, lines 6-20, and column 4, line 62 through column 5, line 6. The disclosed method, coincidentally, bears a striking resemblance to the method disclosed by appellant for purifying IL-2 to homogeneity. For example, we refer to column 5 of Stern [FN2] wherein it is disclosed that the high performance liquid chromatographic process can be carried on with one or more repeats. The first step involves the use of silica gel having octyl groups covalently bonded thereto. The method disclosed by Pestka also involves the use of silica having octyl groups bonded thereto. We find the evulgations in column 4 of Pestka, lines 7-10, and in column 5, lines 3-6, particularly illuminating so we have reproduced them below, respectively:
*5 "The decision as to whether to employ both the octyl bonded glyceryl bonded silica matrix columns and if so what order to select depends in large part on the nature of the protein to be purified."
"It is within the skill of the art to select the proper specific conditions to provide the optimum resolution for each different type of protein to be purified."
The conclusion appears inescapable that one having ordinary skill in the art would have found it prima facie obvious to purify IL-2 to homogeneity, an art-recognized objective, employing Pestka's method, with the reasonable expectation of success in view of Pestka's revelation that proteins are capable of being purified to homogeneity with the disclosed process by one having ordinary skill in the art. In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed.Cir.1986); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed.Cir.1985).
We note that on page 20 of the principal Brief, appellant argues that
"The Examiner has not carried the burden showing that there was an obvious way known in the art for bridging the gap between the partially purified preparations of the art and the ultimate homogeneous preparations of the present invention, a step requiring at least two orders of magnitude of purification."
Apparently accepting the gauntlet cast down by appellant, the examiner imposed a new ground of rejection in his Answer relying upon the previously discussed primary references in view of Pestka. In his responsive Reply Brief, appellant appears to retreat from the issue of whether one having ordinary skill in the art would have found it prima facie obvious to employ Pestka's method to purify IL-2 to homogeneity with a reasonable expectation of success. [FN3] The arguments advanced with respect to Pestka appear on page 2 of the Reply Brief, first full paragraph. Unfortunately, such arguments are directed to the differences between Pestka's process and the process appearing in Stern. However, as noted above, the process employed by appellant appears strikingly similar to that disclosed by Pestka. In addition, Pestka expressly discloses that one having ordinary skill in the art would have been capable of tailoring the disclosed high performance liquid chromatographic process to obtain purification of a desired protein. At any rate, the issue before us is the patentability of IL-2 purified to homogeneity, not the process disclosed in Stern. The examiner has presented a factual basis upon which to logically conclude that one having ordinary skill in the art would have found it prima facie obvious to employ Pestka's process to purify IL-2 with the reasonable expectation of acheiving homogeneity. In re Merck & Co., Inc., supra; In re Longi, supra. We, therefore, agree with the examiner's conclusion that one having ordinary skill in the art would have found the claimed invention prima facie obvious based upon the combined disclosures of any of the applied primary references in view of Pestka.
*6 The evidence of record relied upon by appellant, while relevant to the previously discussed rejections, does not speak to the critical issue generated by the rejection based upon any of the primary references in view of Pestka. In re Longi, supra; In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). We have, of course, considered the long-felt need established by the Stern declaration of October 24, 1983. However, it is our opinion that such evidence is not sufficient to outweigh the evidence of obviousness of record, particularly Pestka. In arriving at this conclusion, we find it significant that Pestka expressly states that the disclosed high performance liquid chromatographic technique is capable of purifying proteins having molecular weights in excess of 12,000 to homogeneity, and expressly discloses that one having ordinary skill in the art would have been capable of tailoring the disclosed process for a particular protein. In addition, we find the similarity between the process disclosed by Pestka and that employed by appellant relevant. The established long-felt need existed prior to the issue date of Pestka, the critical reference, or so close to the issue date of Pestka that it cannot be said with reasonable certainty that those skilled in this art, presumed to be aware of Pestka, were unable to purify IL-2 to homogeneity. Accordingly, based upon the entire record before us, it is our opinion that one having ordinary skill in the art would have found the claimed invention as a whole obvious within the meaning of 35 U.S.C. 103. The examiner's rejection of the appealed claims under 35 U.S.C. 103 as unpatentable over any of Gillis, Frabricius, Welte, Mochizuki, Stadler or either Mier reference in view of Pestka is affirmed.
Pursuant to the provisions of 37 CFR 1.196(b), we impose a new ground of rejection of claim 1 on the doctrine of double patenting of the obviousness type over the claims of Stern. The claimed product apparently results from Stern's claimed process.
Pursuant to the provisions of 37 CFR 1.196(c), appellant is advised that this new ground of rejection can be overcome by an appropriate terminal disclaimer.
Any request for reconsideration or modification of this decision by the Board of Patent Appeals and Interferences based upon the same record must be filed within one month from the date hereof (37 CFR 1.197).
With respect to the new rejection under 37 CFR 1.196(b), should appellant elect the alternate option under that rule to prosecute further before the Primary Examiner by way of amendment or showing of facts, or both, not previously of record, a shortened statutory period for making such response is hereby set to expire one month from the date of this decision. In the event appellant elects this alternate option, in order to preserve the right to seek review under 35 U.S.C. 141 or 145 with respect to the affirmed rejection, the effective date of the affirmance is deferred until conclusion of the prosecution before the examiner unless, as a mere incident to the limited prosecution, the affirmed rejection is overcome.
*7 If the appellant elects prosecution before the examiner and this does not result in allowance of the application, abandonment or a second appeal, this case should be returned to us for final action on the affirmed rejection, including any timely request for reconsideration thereof.
Should appellent elect to adopt the recommendation under 37 CFR 1.196(c), the time within which he may file an amendment for that purpose is hereby set to expire one month from the date of this decision.
37 CFR 1.136(a) does not apply.
AFFIRMED 37 CFR 1.196(b) and (c)
Gordon K. Milestone
Arthur J. Steiner
William F. Smith
FN1. U.S. Patent No. 4,490,298 which issued on December 25, 1984 on appellant's pa rent application.
FN2. See footnote 1.
FN3. It is of interest to note that Pestka and the present application share a common assignee.