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 response is based upon the reply filed 2/27/2026.
Applicant's election with traverse of Group I in the reply filed on 8/25/2025 is acknowledged. The traversal is on the ground(s) the claims have been amended both require similar steps to achieve the effect of determining immune checkpoint blockade therapy (p. 6). The reply asserts that the examiner has not provided a reason why there would be a serious search burden (p 7). . This is not found persuasive because Group II is interpreted as a product and not a method as it is directed towards one or more data processors and a computer readable medium. There is no indication that Group I is performed with the system of Group II. Further, it would be a search burden because as discussed in the restriction requirement, different searches would be required (wet step hybridization assays of Group I versus computer structures of Group II). Furthermore as noted in the requirement for restriction the two inventions are in different classifications (see p. 1),
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-12 are pending. Claims 7-11 have been withdrawn.
The following rejections are maintained with response to arguments following or newly applied necessitated by amendment (35 USC 103).
This action is FINAL.
Withdrawn Objections and Rejections
The claim objections made in the previous office action is withdrawn based upon amendments to the claims.
The 35 USC 112b rejection made in the previous office action is withdrawn based upon amendments to the claims.
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 1-6 and 12 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.
Claims 1, 2-6 and 12 are drawn to determining an immune checkpoint blockade therapy for a tumor based upon measuring expression of a panel of cancer testis antigen (CTA) gene markers and determining CTAB based upon the measurement wherein CTAB greater than or equal to 171 is favorable to response to therapy.
Claim 2 is drawn to predicting a favorable response of the tumor to an immune checkpoint blockade wherein there is a high CTAB (greater than 171) versus a low CTAB (less than 170).
Therefore the claims are drawn to measuring gene expression makers of any CTA gene marker, determining particular burdens, and using the CTAB to functional determine response to immune checkpoint blockade therapy.
Therefore the claims are drawn to a genus of any therapeutic selection of any immune checkpoint blockade therapy in any species based upon expression analysis of any gene considered a CTA gene marker.
The specification states that CTAs may become expressed in cancer cells (p. 1). However, the specification does not define CTA markers nor does the specification describe which makers would be encompassed by the term. Krishnadas (ImmunoTargets and Therapy April 2013 p. 11) teaches some markers that are expressed and considered CTA markers (p. 12 1st column last paragraph). However, Krishnadas et al. has not evaluated any potential CTA gene marker. The specification has not provided critical guidance as to which markers would be considered to be functionally a CTA gene marker. The specificaoin provides examples of these markers (see claim 5), however, the specification has not described which other markers would be encompassed by the term “CTA gene marker”. As such the specification has not described the critical structure of the genus of CTA marker and the functionality of therapy.
The claims are drawn to functionality with any type of cancer. However, the specification does not describe any cancer tumors. Further the art of Krishnada provides that there are CTA rich tumors such as RCC, colorectal cancer and lymphoma and CTA poor tumors such as breast, bladder and prostate cancer (p. 13 2nd column 2nd paragraph). The specification asserts that correlations are especially found in NSCLC (p. 6), however, the specification has not provided guidance that in the breadth of the term “tumor” all of these have a measurable CTAB associated with therapy. In light of the fact that there are different levels of CTA markers in cancers in the prior art, the specification has not describe functionality with regard to the breadth of the term “tumor” and rather any of these cancers would provide the same CTAB levels.
The claims are limited to particular values of CTAB, however, the specification has not provided guidance that these values are correlative in any checkpoint blockade therapy in any tumor based upon expression measurement of any CTA marker panel in any species. Rather the CTAB values provided in Table 1 of the specification appear to be based upon a particular panel of CTA markers (see pages 7-9 of specification).
As shown below, the art teaches that this is a very large genus wherein merely being expressed in one sample is not sufficient to describe the critical features in any other sample.
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. However, as discussed above, the specification provides on particular species and does not provide critical structures for the breadth of the claims.
Further, the art, as recited below, teaches that expression of biomarkers differ in different species. However, the specification has not provided identifying characteristics or functional attributes that would distinguish different members of the claimed genus. Rather, the art teaches that changes in the structure of nucleic acids between species can have an effect on expression. 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).
In the instant case the specification does not provide the skilled artisan with an adequate written description of particular nucleic acids suitable for performing the claimed method as generically encompassed in the claims.
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 CTA markers across species and cancer that functionally detect response to immune checkpoint blockade therapy based upon a CTAB measurement. As such, one of skill in the art would not recognize that applicant was in possession of the genus encompassed by the broadly claimed invention.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the specification describes measuring CTAB and directly links CTAB values to particular therapy (p. 7). The reply asserts that the analysis are preformed across multiple tumor types and cohorts (p. 7). The reply asserts that the skilled artisan would understand based upon the disclosure that high CTAB values are predictive of favorable response to ICB therapy (p 8).
These arguments have been reviewed but have not been found persuasive.
The issue is not the association of a blockade therapy with a particular CTAB level, but rather, which gene markers would be considered CTA gene markers that have a capacity to elicit a cancer specific immune response. The claims are limited to particular values of CTAB, however, the specification has not provided guidance that these values are correlative in any checkpoint blockade therapy in any tumor based upon expression measurement of any CTA marker panel in any species. Rather the CTAB values provided in Table 1 of the specification appear to be based upon a particular panel of CTA markers (see pages 7-9 of specification). Therefore although the specificaoin provides data there is no identication of the critical structures required to determine if another gene is considered a “CTA gene marker have a capacity to elicit a cancer specific immune response” and if these genes in any tumors would predict the sample response to therapy.
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 1-6, 12 are rejected under 35 U.S.C. 101 are rejected under 35 U.S.C. 101 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Note that the unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
Regarding Step 1 of the PEG, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature / natural phenomenon. The claims recite relationship between analyzing CTAB and response to immune checkpoint blockade therapy which would be considered a natural phenomenon. As in Mayo Collaborative Services v. Prometheus, the recited relationship to the disease or condition is a natural phenomenon that exists apart from any human action.
Further the claims require steps of predicting response, determining a therapy (Claim 1) and (determining, characterizing and predicting (claim 2) these steps are considered abstract steps as they encompass mental comparisons to the step of measuring expression.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The steps of analyzing, is not considered an integration as rather, it is using any routine and conventional methods of expression assay analysis. Further, the dependent steps merely limit the types of analysis or known genes in naturally occurring cancer types detected but do not limit the steps themselves to integrate the method and the judicial exception. Claim 12 appears to attempt to limit the claims to integrating to a treatment, however, the administration is to any patient and not based upon integration of the judicial exception. Herein in the instant case it is routine and conventional to treat a patient with cancer with an immune checkpoint blockade therapy.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The additionally recited steps are routine in the prior art. The claims are using a known method of analysis. Morrison et al. (US Patent Application Publication 2018/0107786 April 19, 2018) teaches obtaining a tissue from a tumor and measuring expression of a panel of CTA genes (para 125-128 and table 2). The genes in table 2 include XAGEIB, SSX2, MLANA, MAGEC2, MAGEA12, MAGEA10, MAGEA4, MAGEA3, MAGEA1, GAGE13, GAGE12J, GAGE10, GAGE2C, CTAG2, CTAGIB, and BAGE which are CTA genes. Morrison teaches measuring expression of the markers in table 2 and determining a tumor mutational burden (para 16 and 18).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that CTAB value is a main made metric and not a naturally existing property (p. 10). However, the metric is taking data derived from a naturally occurring gene. Therefore the metric is not adding anything more than the data gleamed from the expression and using algorithms to provide data. The reply asserts that the relationship between analyzing CTAB and response to therapy is not a law of nature because its more than observing or detecting (p. 10-11). The reply asserts that the claims are not limited on observing a correlation but a specific multi step process (p. 11). However, the steps are considered general, routine steps. The steps of obtaining tissue and measuring expression are generally methods of performing expression assays that are known in the prior art. Furhtermore the step of predicting appears to be a mental step of performing data analysis. Step e appears to be the recitation of the judicial exception. The reply asserts that the determining step cannot be performed practically as it would require vast quantities of data (p. 12). However, the claims do not require any particular number of genes and can be interpreted as two genes. Furthermore, the fact that the data is large does not limit it to more than a mental step that can be performed with a pencil and paper.
The reply asserts that there are additional steps that inventive in combination (p. 13-14), however, as noted above these steps are considered routine steps that can be performed using commercially available expression assays.
The reply asserts that the claims provides an improvements to the technical field of cancer therapeutics by providing a reliable indicator (p. 9). The reply asserts that the experimental data is provided in table 2 (p 9). The reply has not pointed to any specific limitation in the claims that are the improvement or that directly leads to the improvement. The data from table 2 is a different scope than what is claimed by claim 1 which does not provide any particular gene expressions The reply appears to be arguing that the CTAB is an improvement, however, the calculation steps are general recited statistical steps of summing. In particular gather data, quantify specific subtypes of date, normalize, compute variants, and compare to a threshold. The reply has not pointed to which of these general data gathering steps are the improvement.
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) 1, 3-6 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Morrison et al. (US Patent Application Publication 2018/0107786 April 19, 2018)
With regard to claim 1, Morrison et al teaches obtaining a tissue from a tumor and measuring expression of a panel of CTA genes (para 125-128 and table 2). The genes in table 2 include XAGEIB, SSX2, MLANA, MAGEC2, MAGEA12, MAGEA10, MAGEA4, MAGEA3, MAGEA1, GAGE13, GAGE12J, GAGE10, GAGE2C, CTAG2, CTAGIB, and BAGE which are CTA genes. Morrison teaches measuring expression of the markers in table 2 and determining a tumor mutational burden (para 16 and 18). Absent a definition in the specification of CTAB this term is considered a tumor burden of the recited markers. Morrison et al. teaches summing based upon expression rank (para 81). Morrison et al. teaches predicting response to an immune checkpoint blockade therapy (para 50, 63, 106). Morrison et al. does not teach that the CTAB is 171, however, this limitation appears to be conditional as it is only required when there is a predictable favorable response. As such the phrase does not appear to limit the step of the claims. Morrison et al. suggests that one administer ipilimumab (immune checkpoint blockade therapy) to patients which have particular burdens (para 96-106) a therefore it would be prima facie obvious at the time of the effective filing date to determine therapy response and administer a treatment which would treat particular patients that are considered responsive.
With regard to claim 3, Morrison et al. teaches that the markers are measured by RNA-seq (para 107 and 126-127).
With regard to claim 4, Morrison et al. teaches that the tumor is a NSCLC tumor (para 130-131).
With regard to claim 5, Morrison teaches the genes in table 2 include XAGEIB, SSX2, MLANA, MAGEC2, MAGEA12, MAGEA10, MAGEA4, MAGEA3, MAGEA1, GAGE13, GAGE12J, GAGE10, GAGE2C, CTAG2, CTAGIB, and BAGE
With regard to claim 6 and 12, Morrison et al. teaches administration of ipilimumab (para 96-106).
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that Morrison teaches response based upon a different immune score and does not teach that CTAB is greater than 171 (p. 16). The reply asserts that the languages is not conditional but provides a specific threshold (p. 16). These arguments have been reviewed but have not been found persuasive. Claim 1 only requires determining CTAB by summing a gene expression rank. Morrison et al. teaches summing based upon expression rank (para 81). As such even though Morrison et al. does not teach that CTAB is 171, it does teach the method step of C. Therefore is not requirement that this measurement is compared to any threshold or determination if that the CTAB measured is greater than or less than 171. As such based upon the breadth of the claims, the rejection has been maintained.
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.
Claim 1-6 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16-19, 36-39, 41-46 of copending Application No. 18883641 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each application requires an analysis of CTA burden based upon the sample CTA gene makers and determining an immune checkpoint blockade therapy for the tumor.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The reply does not provide any particular arguments and therefore the rejection has been maintained.
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
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