Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE HENRY A. ERLICH AND LINDA J. NYARI
Appeal No. 624-56
August 18, 1986
Application for Patent filed November 30, 1981, Serial No. 325,969, a continuation-in-part of Serial No. 234,508, filed February 17, 1981, abandoned. Production of Monoclonal Antibodies for Human Fibroblast Interferon.
Albert P. Halluin et al. for appellants
Primary Examiner--Lionel M. Shapiro
Before Serota, Pellman and W. Smith
This is an appeal from the final rejection of claims 1 to 17. Claims 3 and 14 were cancelled in an amendment filed under 37 CFR 1.116. Thus, claims 1, 2, 4 to 13 and 15 to 17 are the claims remaining on appeal.
The present invention involves the use of hybridoma technology to produce monoclonal antibodies specific for human fibroblast interferon. The scope of protection sought for this invention includes claims directed toward the method of making monoclonal antibodies, the hybrid cell lines produced and used in this method, the monoclonal antibodies produced, and the uses of the monoclonal antibodies in isolating and purifying or identifying human fibroblast interferon.
Claims 1 and 4 through 8 are illustrative of the invention and read as follows:
1. Continuous cell lines producing antibodies specific for human fibroblast interferon which comprise fused cell hybrids derived from human fibroblast interferon primed vertebrate antibody producing cells and cancer cells.
5. Continuous cell lines of Claim 1 comprising fused cell hybrids selected from the group consisting of CE/F 11 (HB 8043), CE/F 12 (HB 8044), CE/F 13 (HB 8045), CE/F 14 (HB 8046), CE/F 15 (HB 8047), CE/F 16 (HB 8048) and their progeny.
6. A process for using monoclonal antibodies of Claim 4 to isolate and purify human fibroblast interferon.
7. A process for using monoclonal antibodies of Claim 4 to identify human fibroblast interferon.
8. A method for producing monoclonal antibodies specific for human fibroblast interferon comprising:
(a) immunizing an animal with human fibroblast interferon;
(b) harvesting an antibody producing organ from said immunized animal;
(c) preparing a cellular homogenate from said organ;
(d) fusing said cellular homogenate with cultured cancer cells;
(e) selecting hybrid cells which produce monoclonal antibody specific for human fibroblast interferon;
(f) maintaining said hybrid cells so that they reproduce perpetually; and
(g) harvesting monoclonal antibodies specific for human fibroblast interferon produced by said hybrid cells.
The references relied upon by the examiner are:
Ganfield et al. (Ganfield) 4,311,639 Jan. 19, 1982
Secher et al. (Secher) 4,423,147 Dec. 27, 1983
*2 Nyari et al. (Nyari), Presentation at TNO (Elsevier) THE BIOLOGY OF THE INTERFERON SYSTEM, International Conference, Rotterdam, April 21-24 (1981) p. 67(5).
Stewart, INTERFERONS AND THEIR ACTIONS, CRC Press, Inc., Cleveland, (1977) p. 58.
Kearney et al. (Kearney), J. Immunol. 123:4, 1548 (1979).
Secher et al. (Secher), Nature 285, 446 (1980).
Weissenbach et al. (Weissenbach), Proc. Natl. Acad. Sci. 77:12, 7152 (1980).
Plant et al. (Ed.), Banbury Report 10, PATENTING OF LIFE FORMS, Cold Spring Harbor Laboratory (1982) pp. 188-189.
A new reference cited by the Board is:
Sevier et al. (Sevier), MONOCLONAL ANTIBODIES IN CLINICAL IMMUNOLOGY, Clin. Chem. 27:11, 1797-1806 (1981).
The following rejections are presented in the examiner's answer:
I. Claims 1, 2, 4 to 13 and 15 to 17 are rejected under 35 USC 103 as unpatentable over Ganfield, Stewart or Nyari in view of Kearney, Secher [the patent or the article] or the admitted state of the art at page 7 of the specification.
II. Claim 4 is rejected under 35 USC 102(a) as anticipated by Nyari and claims 1, 2, 5, 8 to 13 and 15 to 17 are rejected under 35 USC 102(a) as anticipated by or under 35 USC 103 as unpatentable over Nyari.
III. Claims 6 and 7 are rejected under 35 USC 112, second paragraph as being incomplete in that they fail to recite a positive method step.
IV. Claims, 1, 2, 4 to 13 and 15 to 17 are rejected under 35 USC 112, first paragraph, as being nonenabled in that the original disclosure does not set forth the amount of human fibroblast interferon used in one of the screening assays used to determine production of monoclonal antibodies by hybrid cell lines.
V. Claims 5 is rejected separately under 35 USC 112, first paragraph, as being nonenabled in that appellants have not assured that the hybrid cell lines set forth in claim 5 have been deposited under such conditions and assurances that these cell lines will be 'permanently' available upon the granting of a patent on the invention.
Effective Filing Date of the Claims on Appeal
This application was filed on November 30, 1981 and is stated to be a continuation-in-part (cip) of Application Serial No. 06/234,508, filed February 17, 1981. Under the applicable administrative guidelines set forth in § 201.08 of the Manual of Patent Examining Procedure (M.P.E.P.), the examiner is to assume that the claims of a cip application are entitled to the filing date of the parent application(s) under the provisions of 35 USC 120 unless there is a need to actually determine such entitlement due to the presence of an intervening reference. Here, we have three intervening references relied upon by the examiner, viz., U.S. Patent No. 4,423,147 to Secher, patented December 27, 1983, while having a date for the purpose of 35 USC 102(e) of December 10, 1981 as defined in 35 USC 363, was published as W081/02899 on October 15, 1981; an abstract of a paper presented at the Proceedings of the International Meeting of the Biology of the Interferon System, held in Rotterdam, The Netherlands, on April 21-24, 1981, by Nyari, Tan and Erlich [FN1] (Nyari) and the actual paper presented at that meeting by Nyari [FN2]. The abstract and paper are directed to the subject matter of the present invention.
*3 Appellants contend at page 1 of the main brief that the claims on appeal are entitled to the filing date of Serial No. 06/234,508 of February 17, 1981 and this contention has not been disputed by the examiner. In reviewing this record, we find that the examiner has not explicitly stated an opinion as to whether the claims on appeal are entitled to the earlier filing date of February 17, 1981 under 35 USC 120 and that the actions taken by the examiner in this application present a somewhat confusing picture as to which filing date the examiner considers the appealed claims are entitled. The examiner withdrew rejections under 35 USC 102 and 103 based upon other intervening references [FN3] view of appellants' assertion that the rejected claims [FN4] were entitled to the earlier filing date of February 17, 1981 while maintaining the rejection IV under 35 USC 112, first paragraph, for nonenablement, the reasons for which would be applicable to the parent application, Serial No. 06/234,508 [FN5]. Thus, it is necessary to consider the nonenablement rejection IV to determine to which filing date the appealed claims are entitled.
As set forth above, the present invention is directed toward the production of monoclonal antibodies specific for human fibroblast interferon. The basic method for producing monoclonal antibodies for a specific antigen was developed by G. Kohler and C. Milstein and was published by them in 1975. Since Kohler and Milstein made public their basic method, there has been a veritable explosion of research applying this basis method to obtain monoclonal antibodies specific to a wide variety and number of antigens. Appellants acknowledge this and set forth a very helpful background of the development and history of monoclonal antibody research on pages 1-9 of the present specification. There is no dispute that the present method of producing monoclonal antibodies specific for human fibroblast interferon as recited in claim 8 parallels step by step the process of Kohler and Milstein.
The part of this process that the examiner considers to be nonenabled involves the screening step in which the hybrid cells (hybridomas) formed in the fusion step are screened for the desired antibody production. Appellants disclose that they have developed a preliminary screening step to identify which hybridomas produce the desired monoclonal antibody. As disclosed in Example I of this application, appellants use a solid phase radioimmunoassay (RIA) for this preliminary screening that uses an amount of partially purified human fibroblast interferon. Example I states that 30 <<MU>> ??Illegible Text?? 1 of the partially purified human fibroblast interferon is used in this assay. The examiner argues that this volumetric amount does not enable one to use this assay in that the artisan needs to know the quantitative amount of the interferon in order to perform this assay. Appellants argue that the actual quantitative amount used does not need to be known in that the assay is designed to simply be a yes/no type assay to detect the presence of monoclonal antibodies specific for human fibroblast interferon. Insofar as the lack of disclosure of the quantitative amount of human fibroblast interferon used in this preliminary assay screening would raise a question of enablement in this application, it would raise a more serious question in the parent application, Serial No. 06/234,508 since that application does not even disclose the volumetric amount of 30 <<MU>> ??Illegible Text??1, only the use of an undisclosed amount of partially purified human fibroblast interferon in the preliminary screening assay.
*4 However, we find that this issue is in fact a nonissue when the claims on appeal are analyzed. As set forth above, the assay in question is a preliminary assay useful in the screening procedure to identify the most probable hybridomas for further investigation. The six hybridomas identified via this preliminary screening in Example I were then further assayed in Examples II and III using such standard techniques as an antiviral assay. Since claim 8, step (e) recites, 'selecting hybrid cells which produce monoclonal antibody specific for human fibroblast interferon,' the claim in issue does not require a preliminary screening step such as that of Example I and, in fact, reads upon performing the selecting step via the use of a conventional antiviral assay. Such an antiviral assay is also disclosed in Example III of the parent application, Serial No. 06/234,508. Thus, whether the preliminary screening step of Example I of this or the parent application is disclosed in sufficient detail to enable one to practice that assay is not an issue that we need to decide since (1) the record is clear that one of ordinary skill in the art may screen the hybridomas produced in the present invention for monoclonal antibody production using other, well-known assays; and (2) the claims on appeal do not require the use of the assay in dispute.
The present disclosure as well as that of the parent application does enable one of ordinary skill in the art to practice the claimed invention. Thus, the claims on appeal are disclosed in the manner provided by 35 USC 112, first paragraph, in Serial No. 06/234,508, and we reverse this rejection of the claims. Accordingly, the claims on appeal are entitled under 35 USC 120 to the benefit of the filing date of the parent application of February 17, 1981.
Based upon this filing date, the Nyari abstract and paper [FN6] and the Secher patent and corresponding PCT document W081/02899, [FN7] as well as the Hochkeppel references previously withdrawn, are not prior art to the appealed claims. Therefore, rejection II, as set forth above, and rejection I, insofar as it relies upon Nyari and the Secher patent, are reversed.
Rejection under 35 USC 103 Using Ganfield, Steward, the Secher Publication
and the Admitted State of the Art
We will affirm this rejection.
At the time this invention was made, the prior art included the teachings of (1) Stewart and Ganfield that human fibroblast interferon and human leukocyte interferon are antigenic; (2) the basic method of Kohler and Milstein, as set forth on page 7 of the specification, of forming and harvesting monoclonal antibodies specific to known antigens comprising:
(b) harvesting an antibody producing organ of the immunized animal (spleen);
(c) preparing a homogenate of the cells of the harvested organ;
*5 (d) fusing these cells with cancer cells;
(e) selecting the hybrid cells producing the monoclonal antibody specific for that antigen;
(f) growing the selected hybrid cells; and
(g) harvesting the monoclonal antibodies produced by the selected growing hybrid cells;
and (3) Secher that the technique of Kohler and Milstein may be applied to human leukocyte interferon and successfully produce monoclonal antibodies specific for human leukocyte interferon while overcoming difficulties in regard to the screening step. Secher also discloses the use of monoclonal antibodies specific for interferon in separating and/or identifying the interferon for which they are specific.
We find that the claims on appeal differ from the above described prior art only in the use of human fibroblast interferon as the starting antigen in immunizing the animal. However, it is our finding that once the antigen of interest is selected, the use of that antigen in the known method of Kohler and Milstein will result in the expected hybrid cell lines and the specific monoclonal antibodies.
The level of skill in this art is adequately represented by the Secher publication which shows that the basic method of Kohler and Milstein may be readily used and adapted for various antigens such as an interferon. If further evidence of the level of ordinary skill in the art is needed, we point to Sevier. This reference was published after the effective filing date of the claims on appeal but does, in Table 2, tabulate research results reported in various publications having dates prior to or just at the time the present invention was made, i.e., February 17, 1981 [FN8]. It is this tabulation at pages 1798 and 1799 that we find of interest in establishing the level of skill of the ordinary person in this art. Table 2 is a listing of monoclonal antibodies made against clinically important antigens. At page 1798, Table 2 is explained as follows:
The list of hybridoma antibodies made against clinically important antigens is growing at a rapid pace (44). Abstracts of biological and immunological meetings reflect the coming avalanche of monoclonal reagents. In Table 2 we list some of the reported monoclonal antibodies made to mainly human antigens, and their references, merely as a starting place for the interested reader. We have not included most of the references to cell-surface antigens found on normal human lymphocytes (for reviews, see 45-51).
Thus, at the time this invention was made, the level of skill in the art of producing monoclonal antibodies in accordance with the teachings of Kohler and Milstein had rapidly progressed from the publication of their seminal work to the point where the method had been used to produce numerous monoclonal antibodies specific to a variety of antigens.
From our analysis, we find that it would have been obvious to one of ordinary skill in the art at the time the present invention was made to use the basic method of Kohler and Milstein to form monoclonal antibodies specific for human fibroblast interferon since human fibroblast interferon was a known antigen (Ganfield, Stewart) of unquestioned research interest as an antiviral or antitumor agent. One would have approached this project with a reasonable expectation of success in view of the Secher publication in that the Secher publication evidenced that one may successfully adapt the Kohler and Milstein method to produce monoclonal antibodies specific for a human interferon.
*6 Our finding of obviousness extends to all of the claims on appeal since the selection of human fibroblast interferon as the starting antigen will lead to the formation of hybrid cell lines that produce monoclonal antibodies specific for human fibroblast interferon. The specifically identified hybrid cell lines of claim 5 are also included in this finding since they are identified only by the process from which they were made (i.e., fusion of primed antibody producing cells and cancer cells) and by the product they produce (i.e., monoclonal antibodies specific for human fibroblast interferon). The present record does not contain any evidence that these specific cell lines differ in any significant manner or produce monoclonal antibodies that differ in any aspect or degree from the hybrid cell lines that would be expected to be formed in using human fibroblast interferon as the starting antigen in the basic method of Kohler and Milstein.
We note that appellants do not separately argue the dependent claims so they stand or fall based upon the limitations found in the independent claims. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Appellants argue that there is a degree of unpredictability in this art, stating:
There is a degree of unpredictability between different animals in producing antibodies in response to a given antigen, e.g., interferon. For example, it is not obvious that an immune reaction which will result upon injection of interferon into a rabbit for the production of polyclonal antibodies will also work when injected into a mouse. Even if the animal does develop an immune response, there is still the difficult task of growing hybridoma cells in culture which are capable of secreting interferon directed monocolonal antibodies.
Realizing that there is a distinct difference between polyclonal and monoclonal antibodies, it can be further shown that the production of a monoclonal antibody directed to a specific type of interferon does not imply that one can easily produce monoclonal antibodies for each type of interferon.
Applicants respectfully submit that while the Kearney, et al. reference teach the production of mouse monoclonal antibodies, and the Secher et al. reference teach the production of monoclonal antibodies to human leukocyte (alpha) interferon, neither teach the production of monoclonal antibodies to human fibroblast (beta) interferon. The interferons represent a complex family of proteins with a variety of biological activities. Because each interferon ('<<alpha>>' '<<beta>>' '<<gamma>>' ??Illegible Text??) has its own unique set of properties, the production of monoclonal antibodies to one type of interferon would not make it obvious that other interferons would possess the same immunologic traits.
These factors are further supported by the Secher, et al. reference wherein only one monoclonal antibody capable of recognizing leukocyte interferon was produced despite the large number of growing hybridoma cells generated (emphasis in original). Brief, pp. 4-5)
*7 We do not necessarily disagree with the statements made by appellants in that, quite clearly, each type of animal may have a different response to each antigen and each type of interferon may give a different immune response. However, we disagree with the conclusion appellants reach based upon these statements. The level of skill in this art had developed sufficiently since the publication in 1975 of the work of Kohler and Milstein that one having all of the applied references before him at the time the invention was made, would have proceeded to produce monoclonal antibodies specific for human fibroblast interferon with a reasonable expectation of success. We view the teachings of Secher as being opposed to those of appellants. The success of Secher in obtaining monoclonal antibodies specific for one type of human interferon, while overcoming the problems disclosed in the reference, would have led one to produce monoclonal antibodies specific to human fibroblast interferon using the same method with a reasonable expectation of success. The problems disclosed in the present specification encountered in this invention are the same as those encountered and overcome by Secher and no doubt are similar to those encountered and surmounted by the various researchers identified in Table 2 of Sevier. It is true, as argued by appellants, that Secher identified only a single hybridoma that produced the desired antibody. However, we view this as supporting the present case for obviousness since Secher overcame the same problems encountered by appellants and succeeded. We fail to find any significance in the number of hybrid cells produced by Secher at the fusion step since it is expected that a large number will be produced and will be screened for antibody production. The obtention of a large number of hybrid cells at the fusion step and the necessity of screening them for the desired antibody production has been routine in this art since the work of Kohler and Milstein. The screening of the large number of hybrid cells may have been tedious and laborious, but it was a necessary step undertaken by the researchers in this field. The screening step recited in claim 8 does not differ from those of the prior art, including that of Secher.
We recognize that a previous panel of this Board has considered issues related to monoclonal antibodies. See Ex parte Old, 229 USPQ 196 (PTO Bd. App. and Inter. 1985). On the facts of record in the earlier case, that panel reversed the rejection before it, finding a degree of unpredictability in the use of malignant human renal cells as the antigenic determinant. Here, we have no doubt that, in view of the facts of record in this case at the time this invention was made, one of ordinary skill in the art would have been motivated to produce monoclonal antibodies specific for human fibroblast interferon using the method of Kohler and Milstein with a reasonable expectation of success. Obviousness under 35 USC 103 does not require absolute predictability. In re Kronig, 539 F.2d 1300, 190 USPQ 425 (CCPA 1976); In re Farnham, 52 CCA 1118, 342 F.2d 455, 144 USPQ 746 (1965); In re Moreton, 48 CCPA 875, 288 F.2d 708, 129 USPQ 227 (1961).
*8 Appellants also argue that the Patent and Trademark Office allegedly recognizes the inventive uniqueness of each type of monoclonal antibody by pointing to the Secher patent. This argument is without merit in that each case is determined on its own merits. In re Gyurik, 596 F.2d 1012, 201 USPQ 552 (CCPA 1979; In re Atwood, 46 CCPA 901, 904, 267 F.2d 954, 956, 122 USPQ 378, 380 (1959); In re Freedlander, 30 CCPA 1179, 1181, 136 F.2d 759, 760, 58 USPQ 402, 403 (1943). This rejection is affirmed.
Rejection of Claims 6 and 7 under 35 USC 112, Second Paragraph
The examiner has alleged that these claims are incomplete since they do not recite any steps. Appellants argue in the supplemental appeal brief that these claims need not specifically outline any process steps, citing Ex parte Bull, 117 USPQ 302 (PTO Bd. App., 1957). We agree with the examiner that appellants' reliance upon Bull is misplaced because the claims under consideration in the prior appeal did recite active, positive steps such as 'bringing together . . .,' 'providing,' and 'maintaining.' .Here, claims 6 and 7 merely recite a use without any active, positive steps delimiting how this use is actually practiced. While we agree with appellants that the claims need not recite all of the operating details, we do find that a method claim should at least recite a positive, active step(s) so that the claim will 'set out and circumscribe a particular area with a reasonable degree of precision and particularity,' In re Moore, 58 CCPA 1042, 439 F.2d 1232, 169 USPQ 236 (1971); and make it clear what subject matter these claims encompass, In re Hammack, 57 CCPA 1225, 1230, 427 F.2d 1378, 1382, 166 USPQ 204, 208 (1970), as well as making clear the subject matter from which others would be precluded, In re Hammack, supra, 57 CCPA at 1231, 427 F.2d at 1382, 166 USPQ at 208. Without reciting any active, positive steps, claims 6 and 7 fail to achieve these purposes. This rejection is affirmed.
Rejection of Claim 5 under 35 USC 112, First Paragraph
At issue in this rejection is whether appellants have sufficiently satisfed the requirement that certain biological material that is determined to be needed under 35 USC 112, first paragraph, to practice inventions in the biotechnology field, such as the present invention, be deposited in a depository so that the public will have access to the biological material needed to practice the invention if a patent is issued on the invention.
This specific rejection was newly made in the examiner's answer. The examiner does not question that the six hybrid cell lines in issue were in fact deposited in an appropriate depository, but, rather, the examiner asserts that appellants have not assured permanent availability of these hybrid cell lines to the public should a patent issue.
*9 The Court of Appeals for the Federal Circuit has recently spoken toward this deposit requirement in In re Lundak, 773 F.2d 1216, 227 USPQ 90 (Fed. Cir. 1985). The issue decided by the Court was whether a required deposit of biological material must be made prior to filing the subject application. The Court concluded on the record before it that the deposit of the biological material that was made after the application was filed but before the patent issued would meet the requirements of 35 USC 112, first paragraph.
In considering that holding and the present facts, we find that we need not decide this issue at this time as (1) it is not fully developed by the examiner and appellants; and (2) the claim in issue has not been indicated to be allowable.
As stated above, the examiner made this rejection as a new ground of rejection in the examiner's answer. The examiner's statement of the rejection is essentially his conclusion that the proper assurances in regard to permanent availability had not been made of record. The examiner's statement of the rejection did not take into account the declaration by Linda J. Nyari, filed June 16, 1983, Paper No. 3, which addressed previous problems raised by the examiner in regard to the deposit requirement, as to why the statements in that declaration did not satisfy the 'permanency' requirement. Nor did the examiner's statement of this rejection include any guidance as to what the examiner would consider an appropriate assurance of 'permanent' availability. Appellants responded to this new ground of rejection in the reply brief, asserting that the Nyari declaration does assure permanent availability of the deposited cell line. The examiner 'noted' this reply brief but did not enter a supplemental examiner's answer in response to appellants' assertions. Thus, we may assume that the examiner did not find said assertions to be convincing but we, as well as appellants, are without the benefit of the examiner's opinion as to why they are not convincing. Thus, we find that it would be premature to decide this issue, especially because the rejected claim has not been indicated to be allowable. If further prosecution is had on the subject matter herein, we trust that the parties will better define this issue with at least the examiner explaining his position as to 'permanently' available and/or stating why the assurance by appellant Nyari in her declaration as argued in the reply brief is not adequate.
To summarize, we find:
(1) The claims on appeal are entitled under 35 USC 120 to the earlier effective filing date of parent application, Serial No. 06/234,508 of February 17, 1981; (2) Based upon this earlier effective filing date, the Nyari abstract, the Nyari paper, the Secher patent and the Secher PCT publication are not prior art to the claims on appeal; (3) The appealed claims would have been obvious under 35 USC 103 in view of the teachings of Ganfield, Stewart, the Secher publication and the admitted state of the prior art on page 7 of the specification; (4) Claims 6 and 7 are indefinite under 35 USC 112, second paragraph; (5) The issue raised in regard to the deposit requirement of the six hybrid cell lines of claim 5, as well as the corresponding rejection under 35 USC 112, first paragraph, is not ripe for decision; and (6) The claims on appeal are enabled under 35 USC 112 since they do not require the disputed preliminary screening assay of Example 1.
*10 The decision of the examiner is affirmed.
BOARD OF PATENT APPEALS AND INTERFERENCES
Saul I. Serota
Irving R. Pellman
William F. Smith
FN1. Nyari and Erlich are the named inventors of this application.
FN2. The examiner has expressed a concern that this abstract may have been published before the meeting on April 21-24, 1981. Appellants stated in the supplemental brief and reply brief that the abstract was not published prior to this meeting. The examiner has not presented any evidence that places this assertion in question. On the record before us, we find the publication date of the abstract and paper to be April 21-24, 1981.
FN3. Hochkeppel et al., Nature, Vol. 291, 500 (June 11, 1981); Hochkeppel et al., Eur. J. Biochem, Vol. 118, 437-442 (September 1981).
FN4. The claims now on appeal are essentially the same as those rejected at that time.
FN5. For the present claims to be entitled to the filing date of Serial No. 06/234,508, 35 USC 120 requires, inter alia, that they be supported in that application in the manner provided by 35 USC 112, first paragraph. Thus, maintenance of this nonenablement rejection is inconsistent with withdrawing the Hochkeppel references as a basis for rejection for the reason given by appellants, viz., that the rejected claims are entitled to the benefit of the earlier filing date.
FN6. The examiner raised an issue concerning the appearance of Tan as a coauthor of the Nyari paper and abstract in regard to authorship and inventorship. In view of our finding that the Nyari paper and abstract are not prior art to the appealed claims, we need not consider this issue.
FN7. The examiner also relies upon a publication of the work of Secher published in June 1980 as a reference. This publication is prior art to the appealed claims under 35 USC 102(a) and is discussed below.
FN8. We note that some of the articles referenced in Table 2 are not technically prior art to the appealed claims. However, the underlying work of even those articles was at or about the same time this invention was made. Contrast this to the Banbury article relied upon by the examiner which was not published until 1982. No evidence has been presented to indicate that the remarks attributed to Dr. Watson in that article are reflective of the skill in the art at the time this invention was made.