DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to papers filed 1/16/2026.
Applicant’s election of Group II, nucleic acids, and the combination of S100A2, GCNT3, CXCL6, MMP10 in the reply filed on 7/31/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). This restriction requirement has been made final.
Claims 5,8-9,11,13-15, 26-33 are pending. Claims 1-4,6-7,10,12,23,16-25 have been cancelled.
Claims 26-33 are withdrawn as being drawn to a nonelected invention.
The following rejections are maintained (35 USC 112a) or newly applied as necessitated by amendment (35 USC 112b) with response to arguetmsn following.
This action is FINAL.
Withdrawn Rejections
The 35 USC 112b, 35 USC 112d, 35 USC 102 rejection made in the previous office action is withdrawn based upon amendments to the claims.
Modified Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5,8-9,11,13-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting a decreased expression of S100A2, GCNT3, CXCL6, and MMP10 and DDR2 knockdown , does not reasonably provide enablement for treating any subject comprising administering an effective amount of PD-1 or anti PD-1 ligand antibody for treating bladder, lung or a combination of cancers wherein expression levels of a plurality of marker genes having at least 95% sequence identity, homologs, or variants of S100A2, GCNT3, CXCL6, MMP10 below a reference value. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
Breadth of the claims
The claims therefore are drawn to effective amounts of any immune checkpoint inhibitor in any type of subject based upon any expression of S100A2, GCNT3, CXCL6, MMP10, homologs, 95% identity or variants thereof. The specification does not provide guidance of the breath of these claims which would include effectiveness of the recited inhibitors in any subjects based upon expression of a large number of diverse genes fragments which may or may not have variants that effect expression of the recited genes.
Nature of the Invention
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Teachings in the Specification and working examples
The specification asserts that there is an inverse relationship of DDR2 mRNA expression and enriched cellular processes in TCGA bladder cancer patients (para 18). The specification provides associes of DDR expression with immune checkpoint therapy response in human bladder cancer in figures 13A-13J and Figure 17 (para 30 and 34). The specification asserts that there are differentially expressed genes in response to DDR1 and DDR2 expression changes (para 31).
Table 5 disclose that S100A2, GCNT3, CXCL6, and MMP10 are considered DDR2 knockdown related genes. Table 7 discloses that these genes are correlated with high overall survival.
Example 1 discloses that anti PD-1/PDL1 based immune checkpoint therapy provides responses with DDR2 gene signatures in bladder cancer (para 118-122), however, the specification states that DDR2 gene expression did not correlate with response (p. 55).
As such the specification provides a correlation in a particular species and expression of the recited genes expression and anti PD1 therapy, however, the specification does not provide guidance of any immune checkpoint inhibitors in any subject and expression of the recited genes. Further, the specification has not provide any guidance that any variants or homologs of these genes would provide the same phenotypic associations. The specification has not provided which variants and homologs would retain the same association with DDR2 expression. As variant and homologs can encompass changes in the association with biochemical pathways, there is no guidance as to which would have the same correlation to treatments.
The predictability or unpredictability in the Art
Enard et al. (Science 2002 Vol 296 p. 340) teaches that even between closely related species gene expression patterns differ (abstract). Enard et al. teaches that mRNA expression levels are different between humans, chimpanzees, orangutans and rhesus marcques (p. 340 1st column last sentence-2nd column 1st paragraph). Enard et al. teaches that there are a large number of quantitative differences in gene expression in closely related mammals (p. 342 2nd column last paragraph). Therefore the art teaches that even between very closely related mammals there is a divergence of gene expression.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied prior to being able to practice the claimed invention as broadly as written. The skilled artisan would have to determine associations not only with the recited genes and any immune checkpoint inhibitor, but also any homolog or variant thereof. There is no guarantee that these associations in one particular gene set and a specific treatment would provide guidance for any homolog, variant, subject or treatment. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Case law has established that '(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that '(t)he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art". The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genetech Inc. v Novo Nordisk 42 USPQ2d 1001 held that '(I)t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement".
The claims as broadly claim encompass unpredictability wherein the skilled artisan would not be able to make or use the invention as claimed as neither the specificaoin or art provides guidance to the breadth of the claims. .
Accordingly, in view of the unpredictability in the art, and the lack of disclosure in the specification, it would require undue experimentation for one of skill in the art to make and use the claimed invention.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to argument followings. The reply asserts that the specification discloses that the gene signature was a prognostic tool for lung cancer cohorts and therapy citing para 118 (p. 9-10),. The specification discloses that the artisan would expect that members having 95% sequence identify would have the same properties to the respective gene because of the high degree of structural identity (p. 9-10). These arguments have been reviewed but have not been found persuasive.
It is noted that in paragraph 118 the specification states “DDRE showed mutually exclusive expression pattern in human tumor tissue” however, the claims are not limited to this sample type. Furthermore the paragraph states that DDR1 was able to stratify response in lung cancers but does not provide support for the elected DDR2 gene combination. The reply asserts that there would be the same properties in the genes based upon the high degree of structural identity, however, the reply does not address the embodiments of variants and homologous which would produce fragments that would have structures which would be nonfunctional. The reply has not provided any evidence that this genus would predictably provide the same functionality. Furhtermore, the specification does not provide any guidance to determine which of these fragments would encompass the correlation of treatment response.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5,8-9,11,13-15are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5,8-9,11,13-15 recite “nucleic acids having at least 95% sequence identity with a plurality of genes in Table 5 wherein said table 5 contains genes encoding…”. This recitation is unclear as first it recites table 5, which in the specification is only the genes of S100A2, GCNT3, CXCL6, and MMP10, and then provides that this table “contains” the recited genes. As the claims recite the term “contain” it is not clear if the claims are intending to measure all of the genes recited or if the claims merely intends that the table used must comprise these genes. As such the metes and bounds of the claims are unclear.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682