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 .
Election/Restrictions
Applicant’s election of Group I and the species of IFIT, CSK, SLC39A11 in the reply filed on 12/05/2025 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)).
Claims 1-22 are pending. Claims 2-4, 6-7 and 11-18 are withdrawn as being drawn to nonelected species or invention.
An action in the merits for claims 1, 5, 8-10, and 19-22 is set forth below.
Claim Objections
Claim 22 is objected to because of the following informalities: The term “tot he” should be spelled “to the”. Appropriate correction is required.
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 1, 5, 8-10, and 19-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method predicting a response of a prostate cancer subject comprising determining a gene expression profile of IFIT, CSK, SLC39A11 and determining prediction of prediction of the therapy response and/or the personalization therapy based on the gene expression profile. . The claims therefore encompass any species and any sample and functionally determining any therapy response or any personalization therapy, the specification has not provided that these species would have the same functionality. Further, the specification has not provided a description of any gene expression and any response.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure.
The specification appears to be asserting expression of IFIT, CSK and SLC39A11. The specification uses these genes and expression levels in particular functional algorithms (p. 34-35). The specification does not provide any description of using these expression levels to determine any treatment or any personalized therapy. The specification has not provided which expression levels are associated with these treatments or personalized therapy.
The claims are drawn to any sample or species, that specification provides analysis of prostate cancer human patients. The specification is not clear the sample type, however, the art teaches that different species and samples have different expression levels and that the functionality is not the same for any species or samples. The specification provides different statistical methods for determination of functionality (p. 13-15), however, the specification has not described which expression levels are functionally predictive of therapy response.
The art of Cobb et al (Crit Care Med 2002 Vol. 30 p. 2711) teaches the in analysis of gene expression in spleen and liver sample from septic mice. Notably, the reference teaches that, when compared to a non-septic sample, the relevant expression profiles of the septic mouse spleen and the septic mouse liver contain different nucleic acids at different levels (Table 1; p.2714, middle col., lns.2-8). As such the art teaches that expression levels of the same nucleic acids in different tissue samples differ. Therefore, the art indicates that the identifying characteristics or functional attributes that would distinguish different members of the claimed genus will differ depending on the sample type.
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. As such the specification has not provided written support for the functionality of analyzed data to determine correlations to therapy.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that "Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed." (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.) In the instant case, the specification fails to teach the necessary common attributes or features of the samples and controls consistently in view of the species disclosed. As such, one of skill in the art would not recognize that applicant was in possession of the prediction of radiotherapy response in any sample from any species.
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 1, 5, 8-10, and 19-22 are 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 1, 5, 8-10, and 19-22 are indefinite over “determining at least one of the prediction of the therapy response and /or the personalization of the therapy”. The claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the claims are drawn to determining therapy response and/or personalization of therapy based upon expression profiles however there does not appear to be any particular step to correlate a nucleic acid determination to these responses.
Claims 10 is indefinite over the steps of the claim. The claim is drawn to indication of “negative or positive for the effectiveness”. It is not clear how the terms negative or positive effects the term therapy. In particular it is not clear if the claim intends a particular level of effectiveness of the therapy or some other level of the effectiveness.
“Radiotherapy provided earlier than is the standard” is not clear as it is not clear which radiotherapies would be considered standard. “Radiotherapy with an increased radiation dose” is unclear over the term “increased”. The term is a relative term which renders the claim indefinite. The term increased is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As there is no comparison it is not clear which doses are increased.
The phrase “such as” in section iii of claim 10 is unclear. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 21 is indefinite over the steps of the claim. The claim is drawn to indication of “positive response”. It is not clear how the terms positive effects the term response. In particular it is not clear if the claim intends a particular level of effectiveness of the therapy or some other level of the effectiveness.
Claims 22 is indefinite. “Radiotherapy provided earlier than is the standard” is not clear as it is not clear which radiotherapies would be considered standard. “Radiotherapy with an increased radiation dose” is unclear over the term “increased”. The term is a relative term which renders the claim indefinite. The term increased is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As there is no comparison it is not clear which doses are increased.
Claim Rejections - 35 USC § 112
Claims 1, 5, 8-10, and 19-22 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of one or more of the genes in each of ai-av listed is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different biomarker position. Each biomarker that could be detected is itself located in a separate region of the genome and has its own structure. The nature of genes is that they are differences within a population. The only structural similarity present is that all detected positions are part the nucleic acid structure. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with treatment. For example, the biomarker AIM2 has a distinct chemical structure as compared to, for example, APOBEC3A since the gene can only be understood within the context of the nucleotides, which are structurally dissimilar. Accordingly, while the different markers are asserted to have the property of being indicative of treatment, they do not share a single structural similarity. Nor is the functionality is clear from the very nature of the biomarkers.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5, 8-10, and 19-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation and abstract ideas without significantly more. The claim(s) recite(s) a judicial exception of correlation of prediction of treatment response/personalizing therapy and gene expression. This judicial exception is not integrated into a practical application because the claims require steps of determining expression does not provide a step to integrate the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not integrate the judicial exception to steps that are not considered routine and conventional steps.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation/abstract ideas and routine and convention steps, wherein the routine and convention steps does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge in the prior art as exemplified by the prior (as discussed below).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, a natural phenomenon.
The correlation of expression and determining prediction of therapy or personalization therapy is considered a natural correlation. The step of providing determining the expression in the sample are considered a routine and conventional step as detailed below.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception.
The steps that are not considered judicial expectations are the steps of determining gene expression McClelland et al. (US Patent Application Publication 2011/0236903 September 29,2011) teaches a method of obtaining expression levels of IFIT1, CSK and SLC39A11 in a sample (Table 42, para 3780-382). McClelland et al. teaches that these expression levels can be used for therapy determinations (para 380-385). McClelland et al. teaches that the samples are from patients that have not had treatment for prostate cancer as they do not have prostate cancer (para 7-8). McClelland et al. teaches that the therapy is radical radiation therapy (para 572).
The dependent claims of 8-10,19 only limit the claims to naturally occurring genes, conventional samples that are taught by McClelland et al. or limit the correlation which is considered the judicial exception.
The dependent claim of 5 does not provide more than adding clinical parameters that can be considered conventional knowledge of the patient (for example medical history).
Claims 20-22 does require a step of treating, however, this step is a general “apply it” type claim as the treatment is performed regardless of the prediction. Further these treatments are well known treatments for prostate cancer.
These methods are considered generic recitations of general methods of expression determination that do not overcome the rejection.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1,5,8,9,10,19-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McClelland et al. (US Patent Application Publication 2011/0236903 September 29,2011).
With regard to claim 1, McClelland et al. teaches a method of obtaining expression levels of IFIT1, CSK and SLC39A11 in a sample (Table 42, para 3780-382). McClelland et al. teaches that these expression levels can be used for therapy determinations (para 380-385).
With regard to claim 5, McClelland et al. teaches a method of measuring clinical parameters for therapy determinations (para 145, 192-195).
With regard to claim 8, McClelland et al. teaches that the samples are from patients that have not had treatment for prostate cancer as they do not have prostate cancer (para 7-8).
With regard to claims 9, McClelland et al. teaches that the therapy is radical radiation therapy (para 572).
With regard to claim 10, McClelland et al. teaches associations with therapy, as it is not clear the metes and bounds of the term “positive” McClelland et al. suggests an association that can be considered positive with a therapy recommendation (para 380-385).
With regard to claim 19, McClelland et al. teaches a method of obtaining expression levels of IFIT1, CSK and SLC39A11 in a sample (Table 42, para 3780-382).
With regard to claim 20, McClelland et al. teaches that these expression levels can be used for determination and treating (para 380-385).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over McClelland et al. (US Patent Application Publication 2011/0236903 September 29,2011) in view of Hoffmann et al. (US Patent Application 20170073778 March 16, 2017)
McClelland et al. teaches a method of obtaining expression levels of IFIT1, CSK and SLC39A11 in a sample (Table 42, para 3780-382). McClelland et al. teaches that these expression levels can be used for therapy determinations (para 380-385). McClelland et al. teaches that the samples are from patients that have not had treatment for prostate cancer as they do not have prostate cancer (para 7-8). McClelland et al. teaches that the therapy is radical radiation therapy (para 572).
Therefore McClelland does suggest treatment of radiotherapy and expression screening, but does not teach radical or salvage radiotherapy.
With regard to claim 21-22, Hoffmann et al teaches that salvage radiation therapy associated with gene expression can be detected (para 19, 45, 159 and 171).
Therefore it would be prima facie obvious at the time of the effective filing date to modify the method of McClelland et al. to screen other known radiotherapy methods such as savage radiation therapy to determine gene expression correlations. The ordinary artisan would have a reasonable expectation as Hoffman et all teaches that salvage radiation therapy has an effect on gene expression, in general. As such one would be motivated to determine if the gene expression measured in McClelland radiotherapy includes salvage radiotherapy associations.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1,5,8-10,19-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 18-20 of copending Application No. 18271793 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim steps both are drawn to expression of the same genes and determination of prediction of therapy. Although the applications different in the type of cancer for the subject, the type of cancer does not limit the steps of the claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1,5,8-10,19-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-10 of copending Application No. 18022565 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim steps both are drawn to expression of the same genes and determination of prediction of therapy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1,5,8-10,19-22 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18029748 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim steps both are drawn to expression of the same genes and determination of prediction of therapy. Although the applications different in the type of cancer for the subject, the type of cancer does not limit the steps of the claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682