Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE THOMAS F. DEUEL
Appeal No. 92-0649
January 28, 1993
Application for Patent filed May 24, 1989, Serial No. 356,739; which is a continuation-in-part of application Serial No. 815,685, filed January 2, 1986, now abandoned. Prostate-Derived Mitogen.
Scott J. Meyer et al. for Appellant
Elizabeth C. Weimar
Supervisory Patent Examiner
Gail E. Poulos
This is an appeal from the examiner's final rejection of claims 1 and 2, which are all the claims of the application.
Claim 1 is illustrative of the invention and reads as follows:
1. A purified prostate tissue-derived growth factor having the following characteristics:
(a) molecular weight of about 25 kDa as determined by nonreduced sodium dodecylsulfate polyacrylamide gel electrophoresis,
(b) an amino terminal sequence substantially identical to the amino terminal sequence of the 6 kDa mature rat epidermal growth factor;
(d) cross-reacts with antisera against rat epidermal growth factor; and
(e) mitogenic activity is blocked by anti-epidermal growth factor receptor antisera.
The references relied on by the examiner are:
Tackett et al. (Tackett), Journal of Urology, "Mitogenic Factors in Prostatic Tissue and Expressed Prostatic Secretion," Vol. 133, January 1985, pages 45-48.
Maehama et al. (Maehama), Proceedings of the National Academy of Sciences, USA, "Purification and partial characterization of prostate-derived growth factor," Vol. 83, November 1986, pages 8162-8166.
Appellant's invention relates to a purified growth factor isolated from prostate tissue (Claim 1) and to a method of stimulating the growth of fibroblast cells using the growth factor (Claim 2). Claim 1 defines the growth factor as a proteinaceous material having a molecular weight of about 25,000 Daltons (25 kDa) (subparagraph (a)). Claim 1 further defines the growth factor in relation to a second growth factor known as rat epidermal growth factor (EGF) (subparagraphs (b) through (e)). This requires the claimed growth factor to have an amino (NH2) terminal sequence of 6 kDa which is "substantially identical" to the known amino terminal sequence of the 6 kDa mature rat epidermal growth factor. The claimed growth factor has a potent mitogenic [FN1] activity against NRK cells (normal rat kidney cells). This mitogenic activity is said to be demonstrated by the entire protein rather than by the 6 kDa segment alone (subparagraph (c) of claim 1).
This application, Serial No. 356,739, was filed May 24, 1989 as a continuation-in-part of application Serial No. 815,685 filed January 2, 1986. Both the instant application and the '685 application appear to be concerned with the same prostate-derived growth factor. The '685 parent application describes the growth factor as being derived from frozen rat prostate tissue using the same purification protocol identified as "Protocol 1" in the instant continuation-in-part application. The '685 application did not set forth the amino acid sequence for the protein of interest and, importantly, described the protein itself, without reference to any other protein. Specifically, the '685 application described the protein as having mitogenic activity, a molecular weight of about 25 kDa, certain stability properties, and a particular amino acid content. [FN2]
*2 The instant continuation-in-part application includes all of the subject matter of the '685 application but also includes two additional and different protein purification protocols (Protocols 2 and 3). Protocol 2 also started with rat prostate tissue but used a purification technique which combined both anti-rat EGF immunoaffinity column purification and high performance liquid chromatography (HPLC) of the active fractions from the affinity column.
Purified protein from Protocol 2 was evaluated for amino acid sequence and amino acid composition. The sequence analysis results revealed a similarity between the newly discovered prostate tissue derived growth factor and a previously discovered rat epidermal growth factor. Specifically, the amino terminal sequence of the claimed protein was substantially identical to the amino terminal sequence of the 6 kDa mature rat epidermal growth factor. This "substantial identity" along with certain cross reactivity and blocking data related to epidermal growth factor became subparagraphs (b), (d) and (e) of instant claim 1. In other words, the instant application describes and claims the prostate derived protein not only by its specific characteristics set forth in the patent application but also by its relationship to rat epidermal growth factor.
Appellant also purified the protein using a third protocol which involved ammonium sulfate (NH@4)@2 SO@4 precipitation and purification using CM-Sephadex. After conducting the three purifications and testing the amino acid sequence of the amine termini of at least the peptides produced from protocols 1 and 2 (compare page 22, lines 32-35 and page 26, lines 22-27 of the instant specification), appellant concluded (specification, page 27, lines 16-26) that it was more likely than not that the three separate purification protocols isolated the same 25-kDa EGF-like mitogen and that the 25-kDa polypeptide isolated was most likely the carboxy-terminal portion of the 130-kDa pre-pro [FN3] epidermal growth factor (EGF) and shared amino terminal amino acid sequences with the 6 kDa mature rate EGF. This similarity is set forth in Figure 5 herein.
The Rejections Over Tackett
Appellant's claims stand rejected under 35 U.S.C. § 102 or 35 U.S.C. § 103 over Tackett. We affirm both rejections. The Tackett reference is directed to the purification of mitogenic proteins from human prostatic tissue and prostatic secretions. Appellant has argued that only one of the mitogenic fractions purified by Tackett has a molecular weight at all close to that claimed by appellant. Appellant has made us aware that the "close" fraction was obtained from secretions expressed by the prostate gland, not tissue. Though not argued by appellant, the fraction was derived from human prostatic secretions whereas appellant worked only with rat prostatic tissues.
*3 Appellant has not based his arguments against the rejections on a probable distinction between the amino acid sequences of a rat growth factor and a human growth factor. Accordingly, we must necessarily assume that the claims of the instant case are drafted to cover prostate tissue-derived growth factor of any species so long as it complies with the particular molecular weight and amino terminal sequences, etc. set forth in subparagraphs (a) through (e) of the claims.
The examiner has noted that appellant's claims describe the molecular weight as being "about 25 kDa" and has posited that those skilled in the art would have recognized that molecular weight analysis results are only approximations. From this viewpoint it is reasonable to state that a molecular weight of 30 kDa is essentially the same as one of "about 25 kDa."
Appellant's argument that Tackett's growth factor is derived from prostate gland secretions as opposed to prostate gland tissues as claimed is not persuasive because both factors have the same activity and many organs of the body are known to produce and/or store hormones and other factors which are then released from the organ. Moreover, the examiner's conclusion that the growth factor extracted by Tackett from prostate gland secretions falls within the scope of appellant's claims is not unreasonable based on the similarity in molecular weight and activity of Tackett's factor and that claimed. Indeed, the Tackett reference itself indicates that the lower molecular weight form of the factor found in prostatic secretions, "may represent a form processed for secretion." [FN4] Because the examiner's position is not unreasonable, the burden of persuasion and proofs was properly shifted to appellant to show a lack of anticipation and obviousness. Appellant has not presented any probative evidence that the hormone extracted by Tackett is different from the hormone claimed herein. Counsel's arguments cannot take the place of evidence.
With regard to evidence, we have reviewed the declaration of inventor Deuel and are unpersuaded by his conclusion that the prostate tissue-derived mitogen claimed in the present application and the prostate-derived mitogenic factors disclosed by Tackett are significantly and substantially different materials. Inventor Deuel's arguments are not directed to differences between human and rat growth factors, but, for the most part, are directed to the lack of purity in the Tackett materials. This is not at issue. Inventor Deuel disparages Tackett's work as being virtually meaningless "so far as ... chemical composition or structure is concerned." We recognize that Tackett did not set forth the amino acid sequence for the mitogen described therein. Neither has appellant for the mitogen described and claimed herein.
In the absence of probative evidence regarding a difference between that protein disclosed by Tackett and the 25 kDa mitogens claimed herein, we must affirm the examiner's rejection under 35 U.S.C. § 102. We also affirm the rejection under 35 U.S.C. § 103 because we are in agreement with the examiner that there is a substantial likelihood that the Tackett factor is a species of the claimed mitogenic factors. Anticipation is the epitome of obviousness.
*4 Claims 1 and 2 stand rejected under 35 U.S.C. § 102 and 35 U.S.C. § 103 over Maehama. The Maehama reference is a literature article by inventor Deuel and others. The information in this article corresponds substantially to that set forth in the specification of appellant's parent application. The article was published ten months subsequent to the filing of the parent application but more than one year prior to the filing date of the instant continuation-in-part application.
It is the examiner's position that the protein described in Maehama is the same as the protein claimed herein and, accordingly, anticipates the instant claims. On this point the examiner notes that appellant's claim language, which describes the protein in terms of its amino acid structure and cross reaction characteristics, does not differentiate the protein from that described in the Maehama article, which does not use the amino terminal sequence and cross-reaction characteristics to identify the protein. The examiner is also of the opinion that the claimed protein is so closely related in structure to that of Maehama, that the claimed protein would have been "structurally obvious."
Appellant proffers two somewhat inconsistent arguments against the examiner's positions. First, appellant urges that the Maehama publication constitutes appellant's own work and cannot be used against him because appellant is entitled to a priority filing date for everything disclosed in the parent application. Appellant urges that it is permissible to add disclosure to a parent application when that disclosure would have been obvious to one skilled in the art. Appellant comments that it would be "rank absurdity" to cite a publication against an applicant's claims when that publication has a filing date subsequent to an applicant's priority filing date.
Appellant has also attempted to "swear behind" the Maehama reference via a declaration filed under 37 CFR § 1.131.
With regard to the § 103 rejection over Maehama, appellant has taken a somewhat different tack. Appellant urges that the claims now contain certain sequencing information and relationships to rat epidermal growth factor, and that this is "new matter" which cannot be found in the Maehama reference. Appellant urges that Maehama does not evidence conception, appreciation or recognition of a substantial and significant part of the presently claimed invention.
Assuming, arguendo, that (1) this Board's analysis of the relationship of the instant and parent applications as set forth in the "Background" is correct, and (2) that the protein purified from prostate tissues as described in Protocol 1 of appellant's specification, which protocol is the same as that set forth in the '685 parent application, is the same protein as the protein purified utilizing Protocols 2 and 3, the Maehama reference, which has a publication date of November 1986, subsequent to the January 1986 filing date of the '685 application, would not ordinarily be available as a reference if the instant claims are directed to the same protein set forth in appellant's ' 685 application which protein is now defined using somewhat different descriptive parameters. This conclusion would be consistent with the examiner's position that the amino acid sequence is "an inherent characteristic of the protein" as is antisera binding (Answer, page 9).
*5 However, the language of the claims before us is such that the instant claims are not limited to the same protein described in the parent application but, rather, are broader in scope than what is disclosed in appellant's parent application. This is because the instant claims are of sufficient breadth to encompass proteins other than that described and enabled by the '685 parent application. There are several reasons for this.
First, parent application Serial No. 815,685 described and enabled preparation of a growth factor obtained from "purified rat prostate tissue." Claim 1 herein is not limited to a growth factor obtained from purified rat prostate tissue but, rather, covers any prostate tissue-derived growth factor regardless of species (human, rat, mouse, etc.) or source (tissue or secretions [FN5]). That this is so is evidenced by appellant's Brief which has never challenged the examiner's "anticipation" rejection over the Tackett reference on the grounds that the Tackett reference was directed to a growth factor derived from human prostate secretions [FN6] whereas the claims were directed to a growth factor derived from rat prostate tissue.
Second, subparagraph (b) of instant claim 1 describes the protein as having an amino terminal sequence "substantially identical" to the amino terminal sequence of the 6 kDa mature rat epidermal growth factor. This "substantially identical" limitation broadens the claim to cover more than just the rat tissue growth factor described and enabled by the parent application. On this point see again Figure 5 of the instant application which sets forth the amino terminal sequences for rat, mouse and human EGF. The N-terminal amino sequences may reasonably be said to be "substantially identical," albeit the sequences represent three similar but different factors derived from rat, mouse and humans respectively. Accordingly, interpreted in the light of appellant's disclosure, the phrase "substantially identical" as set forth in subparagraph (b) must necessarily broaden the scope of the claims to include prostate derived growth factors from species other than the rat species of the parent application so long as the amino terminal sequence is "substantially identical" to the amino terminal sequence of the 6 kDa mature rat epidermal growth factor.
Because the instant claims are broader in scope than the invention described in the '685 parent application, the Maehama literature article is available as a reference against the instant claims as a statutory bar thereto (35 U.S.C. § 102(b)) even though it represents appellant's own work.
We empathize with appellant's chagrin at having his own work used against him. However, the law is well settled that the disclosure of a species in a reference is sufficient to prevent a later application from obtaining generic claims unless that reference may be overcome. See § 201.11 of the Manual of Patent Examining Procedure (see page 216, column 2, and the cases cited therein). See also In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) wherein the court stated:
*6 ... the description of a single embodiment of broadly claimed subject matter constitutes a description of the invention for anticipation purposes (see, e.g., In re Ruscetta, 45 CCPA 968, 255 F.2d 687, 118 USPQ 101 (1958), whereas the same information in the specification might not alone be enough to provide a description of that invention for purposes of adequate disclosure. See, e.g., In re Ahlbrecht, supra. There are other apparent anomalies between the requirements for claim-anticipating disclosures and for claim supporting disclosures. See, e.g., In re Hafner, 56 CCPA 1424, 410 F.2d 1403, 161 USPQ 783 (1969). If the law in these situations really produces inequities, the proper remedy is in Congress.
Because we hold the Maehama paper anticipates the subject matter now claimed, we are also of the opinion it would have made the claimed subject matter obvious because anticipation is the epitome of obviousness. [FN7]
Although we have affirmed the examiner's rejection, our reasoning may have changed the basic thrust of the examiner's rejection. Accordingly, we designate this affirmance a new ground of rejection pursuant to 37 CFR 1.196(b).
Our review of this application reveals that appellant's specification has no statement therein regarding the utility of the claimed prostate-derived mitogens. We have also reviewed the references cited by the examiner and find no statement therein regarding the utility of such mitogens. We note that Tackett, pages 47 and 48, indicates that the role of the growth factor in controlling cell division and interactions with other factors was not understood as of 1985. Indeed, editorial comment inserted at the close of the Tackett article indicates that the finding of a growth promoting substance in the prostate and its secretions should not be misconstrued as evidence that it is the agent responsible for prostatic hyperplasia and that the significance of these "factors" was "unclear."
Maehama, page 8166, indicates that the activity of the prostate derived growth factor (PrDGF) is unique and that the mitogen has potential to mediate some of the activities related to prostatic growth, development, and, perhaps hyperplasia and neoplasia. Maehama does not indicate the exact nature of and use for PrDGF's activity. The abstract of the Maehama article indicates that PrDGF differs from other known growth factors in chemical composition and biological properties. We are uncertain regarding whether utility for the claimed mitogenic factors may be arrived at by analogy with other known growth factors.
Because there is no statement of use in the specification, no description in the specification regarding how to use the claimed growth factor, and no exemplification of a use, it would appear that the growth factors claimed herein may lack practical utility and may be unpatentable under ss 101 and 112 of our patent code. Should this application be prosecuted further we strongly urge the examiner to determine whether one skilled in the art would have been able to use the claimed growth factor at the time that either of appellant's parent application or the instant application was filed. This is important because if the parent application did not comply with 35 U.S.C. § 112 from an enablement and "how to use" viewpoint, appellant is not entitled to the benefit of the filing date of the '685 application under 35 U.S.C. § 120 and, accordingly, the Maehama reference would be prior art as to the claimed invention even if the claimed invention were limited to the very same rat prostate-derived protein described in the '685 application. In this regard see
*7 In re Hafner, 410 F.2d 1403, 161 USPQ 783 (CCPA 1969).
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 two months 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.
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.
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
Irving R. Pellman
John T. Goolkasian
FN1. A mitogen is a material which stimulates cell reproduction.
FN2. The amino acid content was set forth in the form of a table listing the amino acids contained in the protein recovered and their relative molar proportion per mole of protein. The amino acid sequence of the protein was not set forth.
FN3. Some hormones (insulin) and growth factors (EGF) are first expressed by the cells as a "pre-pro" protein which contains certain amino acid sequences which are not contained in the hormone or factor as used by the body. These "pre-pro" sequences are normally processed off the protein by the body prior to actual use.
FN4. See footnote 3 herein regarding the body's "processing" of a factor protein.
FN5. A protein secreted from a prostate gland would fall within the category of being "derived" from prostate tissue.
FN6. Clearly human prostate growth factor would not normally be expected to have the same amino acid sequence as rat prostate growth factor. See Figure 5 of the specification which depicts the amino acid sequences of rat, mouse and human EGF as being similar but different.
FN7. We recognize that appellant submitted an affidavit under Rule 131 to overcome the Maehama article as a reference. Such an affidavit is incompetent to overcome the reference because the reference, published November 1986, constitutes a statutory bar under 35 U.S.C. § 102(b). Rule 131 does not apply to overcoming statutory bars.