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 .
Priority
This application filed 07/06/2023 is a Continuation of 17090714, filed 11/05/2020, now U.S. Patent # 11742058, and claims priority from Provisional Application 62931009, filed 11/05/2019. The claims are therefore examined as filed on 11/05/2019, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 13-32 are pending.
Claim 20 is objected to.
Claims 1-12 are cancelled.
Claims 13-32 are examined.
Claims 13-32 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 20 is objected to because of the following informalities:
Claim 20 should read “The method of claim 13, wherein the T-cells comprise CD4+ cells, CD8+ cells, Natural Killer T- Cells (NKT), or a combination thereof.”
Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim Rejection
Claims 13-29 and 32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BLOOM 2019 “Immuno-Oncology Applications Using Next Generation Sequencing” (US 2019018926, as cited on the IDS filed 08/14/2024).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Claim Interpretation and Scope and Contents of Prior Art
Claim 13 recites a method comprising:(a) generating sequencing data from a sample obtained from a subject, said sequencing data comprising expression levels of one or more genes associated with T-cell status. With respect to this limitation, BLOOM teaches methods for generating an immune-oncology profile, comprising generating sequencing data from a sample obtained from a subject to determine gene expression for immune modulatory genes [0003] associated with T-cells [0024].
Claim 13 further recites the limitation of (b) based at least on said expression levels of one or more genes associated with said T-cell status, determining an amount or percentage of T-cells in said sample having a particular status, wherein said particular status of said T-cells comprises naive status, activated status, activation recovered status, terminally exhausted status, progenitor exhausted status, central memory status, effector memory status, stem cell memory status, or a combination thereof. With respect to this limitation, BLOOM teaches determining the amount or percentage of T-cells in the sample having a particular status/cell type based on the expression level, where the status/cell type includes CD4+ naive T-cells, central memory T (Tcm) cells, effector memory T (Tem) cells, CD8+ naive T-cells, and others [0024, Table 3].
Claim 13 further recites the limitation of (c) administering an immunotherapy regimen to said subject, wherein said immunotherapy regimen is identified based at least on said amount or percentage of T-cells having said particular status. With respect to this limitation, BLOOM teaches administering an immunotherapy based on the determined immune-oncology profile/expression of T-cell type [0003, 24, 103].
Claim 14 recites the limitation wherein said generating sequence data comprises performing RNA sequencing. With respect to this limitation, BLOOM teaches performing RNA sequencing [0003].
Claim 15 recites the limitation wherein said RNA sequencing comprises generating cDNA molecules from RNA molecules from said sample. With respect to this limitation, BLOOM teaches generating cDNA molecules from RNA [0003, 7, 10].
Claim 16 recites the limitation wherein said RNA sequencing comprising sequencing said cDNA molecules. With respect to this limitation, BLOOM teaches sequencing the cDNA molecules [0003].
Claim 17 recites the limitation wherein said sample is a bodily fluid sample. With respect to this limitation, BLOOM teaches the sample can be obtained from blood [0003].
Claim 18 recites the limitation wherein said sample is a tumor biopsy sample. With respect to this limitation, BLOOM teaches the sample can be a tumor biopsy sample [0003].
Claim 19 recites the limitation wherein said subject has a head and neck squamous cell carcinoma (HNTSSC), non-small cell lung cancer (NSCLC), or melanoma. With respect to this limitation, BLOOM teaches that the subject can have non-small cell lung cancer, squamous cell carcinomas, or melanoma [0102].
Claim 20 recites the limitation [wherein the] T-cells comprise CD4+ cells, CD8+ cells, Natural Killer T- Cells (NKT), or a combination thereof. With respect to this limitation, BLOOM teaches that the T-cells include CD4+ T cells, CD8+ T cells and natural killer T cells [0024].
Claim 21 recites the limitation wherein said one or more genes associated with T-cell status comprise at least one gene selected from the listed group. Claim 22 similarly recites the limitation wherein said one or more genes associated with T-cell status comprise at least one gene selected from a narrower group. With respect to this limitation, BLOOM teaches that the genes can include at least LEF1, C3AR1, NR4A2, PLXDC1 (Table 5), ZBTB32, CD79A, RASGRP2, TBX21, NR3C2, SLC16A10, CSF2RB, PPP2R2B, GCNT4, VSIG1, CFP, ATP8B4, KLRD1, MAF (Table 2), LAG3 and CD248 [Table 1B], which are listed in the groups of claims 21 and 22.
Claim 23 recites the limitation wherein said one or more genes associated with T-cell status comprise at least 10 genes, and claim 24 similarly recites the limitation wherein said one or more genes associated with T-cell status comprise at least 20 genes. With respect to these limitations, BLOOM teaches that the genes can include the 20 genes listed above.
Claim 25 recites the limitation wherein said immunotherapy regimen comprises an immune cell therapy. With respect to this limitation, BLOOM teaches that the immunotherapy can comprise an immune cell therapy [0003, 24].
Claim 26 recites the limitation wherein said immune cell therapy comprises chimeric antigen receptor T-Cell (CAR-T) therapy, tumor-infiltrating lymphocyte (TIL) therapy, engineered T-cell receptor (TCR) therapy, or natural killer (NK) cell therapy. With respect to this limitation, BLOOM teaches that the immune cell therapy includes CAR-T cell therapy or T cell receptor therapy [0107].
Claim 27 recites the limitation wherein said immunotherapy regimen comprises a checkpoint inhibitor. With respect to this limitation, BLOOM teaches that the immunotherapy regimen includes checkpoint inhibitors [0107].
Claim 28 recites the limitation wherein said checkpoint inhibitor comprises an anti-PD-1 or anti-PD-L1 antibody or antigen binding fragment. With respect to this limitation, BLOOM teaches that the checkpoint inhibitor can comprise an antigen binding fragment or anti-PDL1 such as Atezolizumab, Durvalumab and Avelumab [0107].
Claim 29 recites the limitation wherein said checkpoint inhibitor comprises Enoblituzumab, Ipilimumab, Tremelimumab, Lirilumab, BMS986016, Pembrolizumab, Nivolumab, Pidilizumab, Atezolizumab, BMS-936559, Durvalumab, Avelumab, Bavituximab, or a combination thereof. With respect to this limitation, BLOOM teaches that the checkpoint inhibitor can comprise Enoblituzumab, Ipilimumab, Tremelimumab, Lirilumab, BMS986016, Pembrolizumab, Nivolumab, Pidilizumab, Atezolizumab, BMS-936559, Durvalumab, Avelumab, and Bavituximab [0107].
Claim 32 recites the limitation wherein said sequencing data comprises expression levels of one or more immune modulatory genes. With respect to this limitation, BLOOM teaches determining gene expression level of immune modulatory genes [0003].
Claim Rejections - 35 USC § 103
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.
Claim Rejection
Claims 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over BLOOM 2019 as applied to claims 13-29 and 32 above, and further in view of JIANG 2018 “Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response.
Claim Interpretation and Scope and Contents of Prior Art
BLOOM 2019 teaches the limitations of claims 13-29 and 32 above.
Claim 30 recites the limitation wherein said immunotherapy regimen is identified based at least on the ratio of activated:exhausted T-cells in said sample.
Claim 31 recite the limitation wherein said immunotherapy regimen is identified based at least on an elevated level of exhausted T-cells in said sample.
With respect to these limitations, BLOOM teaches determining cell-type and ratio of T-cells to determine/recommend a treatment regimen [0099] and that the level and ratio of cell subtypes impacted predicts treatment outcomes [0061, 62, 111], but does not specify that treatment is based on the ratio of activated to exhausted T cells or identified based on an elevated level of exhausted T-cells. However, JIANG teaches that the amount of exhausted T-cells impacts the effectiveness of immune checkpoint blockade treatment (pg 1553), so it would be obvious to one of ordinary skill in the art to determine an immunotherapy based on the ratio of exhausted to active T-cells or elevated level of exhausted T-cells in a sample.
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in cancer immunotherapy would have been motivated to combine the teachings of BLOOM with the teachings of JIANG, in order to achieve the claimed invention, because the amount of exhausted T-cells impacts the effectiveness of immune checkpoint blockade treatment (pg 1553) and because exhausted T-cells can be identified by gene expression (pg 1550), such that the methods of BLOOM can be used to identify exhausted T-cells along with other cell types, and this can be used to further inform an immunotherapy decision. A person of ordinary skill would reasonably expect success from combining these teachings, as both BLOOM and JIANG teach methods of gene expression analysis for T-cells to determine immunotherapy outcomes and make advantageous treatment decisions. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
In the interest of compact prosecution, the following rejection under 102, over a non-common inventor prior art reference, is also applied:
Claim Rejection
Claims 13- 32 are also rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by JERBY 2019 “Methods And Compositions For Detecting And Modulating An Immunotherapy Resistance Gene Signature In Cancer” (WO 2019070755 A1, as cited on the IDS filed 08/14/2024).
Claim Interpretation and Scope and Contents of Prior Art
Claim 13 recites a method comprising:(a) generating sequencing data from a sample obtained from a subject, said sequencing data comprising expression levels of one or more genes associated with T-cell status. With respect to this limitation, JERBY teaches methods comprising generating RNA sequencing data from a sample obtained from a subject [0012] and determining expression levels for genes associated with T-cells [0016, 26, 92, 580].
Claim 13 further recites the limitation of (b) based at least on said expression levels of one or more genes associated with said T-cell status, determining an amount or percentage of T-cells in said sample having a particular status, wherein said particular status of said T-cells comprises naive status, activated status, activation recovered status, terminally exhausted status, progenitor exhausted status, central memory status, effector memory status, stem cell memory status, or a combination thereof. With respect to this limitation, JERBY teaches using expression signatures to determine T-cell infiltration level in each tumor [0584] for various T-cell populations, including CD4.sup.+ T cells; naive, cytotoxic, and exhausted CD8.sup.+ T cell subsets; and naive, exhausted, and regulatory CD4.sup.+ T cell subsets [0590, 0609].
Claim 13 further recites the limitation of (c) administering an immunotherapy regimen to said subject, wherein said immunotherapy regimen is identified based at least on said amount or percentage of T-cells having said particular status. With respect to this limitation, JERBY teaches administering an immunotherapy based on T-cell expression [0012- 15, 30, 0177, 613, claim 20].
Claim 14 recites the limitation wherein said generating sequence data comprises performing RNA sequencing. With respect to this limitation, JERBY teaches performing RNA sequencing [0182, 368].
Claim 15 recites the limitation wherein said RNA sequencing comprises generating cDNA molecules from RNA molecules from said sample. With respect to this limitation, JERBY teaches generating cDNA molecules from RNA [0577].
Claim 16 recites the limitation wherein said RNA sequencing comprising sequencing said cDNA molecules. With respect to this limitation, JERBY teaches sequencing the cDNA molecules [0577].
Claim 17 recites the limitation wherein said sample is a bodily fluid sample. With respect to this limitation, JERBY teaches the sample can be from circulating blood [0283, 288].
Claim 18 recites the limitation wherein said sample is a tumor biopsy sample. With respect to this limitation, JERBY teaches the sample can be a tumor sample [0026].
Claim 19 recites the limitation wherein said subject has a head and neck squamous cell carcinoma (HNTSSC), non-small cell lung cancer (NSCLC), or melanoma. With respect to this limitation, JERBY teaches that the subject can have melanoma [0015], head and neck squamous cell carcinoma, or non-small cell lung carcinoma [0307].
Claim 20 recites the limitation [wherein the] T-cells comprise CD4+ cells, CD8+ cells, Natural Killer T- Cells (NKT), or a combination thereof. With respect to this limitation, JERBY teaches that the T-cells include CD8+ T cells and CD4+ T cells [0468, 590].
Claim 21 recites the limitation wherein said one or more genes associated with T-cell status comprise at least one gene selected from the listed group. Claim 22 similarly recites the limitation wherein said one or more genes associated with T-cell status comprise at least one gene selected from a narrower group. With respect to these limitations, JERBY teaches that the genes can include at least EBI3, CD79A, CCR2, CD248, ASB2, LY9, KLRD1 (Table 3), LEF1 (Table 10), CCDC141, ZBTB32, ZBED2, MAF (Table 18), CSF2, IL2, C3AR1 (Table 26), LAG3 [0066], NR4A2, MAL, VSIG1 (Table 26B), CSF2RB, CFP [0068], and MT1G [0062], which are listed in the groups of claims 21 and 22.
Claim 23 recites the limitation wherein said one or more genes associated with T-cell status comprise at least 10 genes, and claim 24 similarly recites the limitation wherein said one or more genes associated with T-cell status comprise at least 20 genes. With respect to these limitations, JERBY teaches that the genes can include 20 of the genes listed above.
Claim 25 recites the limitation wherein said immunotherapy regimen comprises an immune cell therapy. With respect to this limitation, JERBY teaches that the immunotherapy can comprise an adoptive cell transfer, an immune cell therapy [0049].
Claim 26 recites the limitation wherein said immune cell therapy comprises chimeric antigen receptor T-Cell (CAR-T) therapy, tumor-infiltrating lymphocyte (TIL) therapy, engineered T-cell receptor (TCR) therapy, or natural killer (NK) cell therapy. With respect to this limitation, JERBY teaches that the immune cell therapy includes CAR-T cell therapy [0049].
Claim 27 recites the limitation wherein said immunotherapy regimen comprises a checkpoint inhibitor. With respect to this limitation, JERBY teaches that the immunotherapy regimen includes checkpoint inhibitors [0014-15].
Claim 28 recites the limitation wherein said checkpoint inhibitor comprises an anti-PD-1 or anti-PD-L1 antibody or antigen binding fragment. With respect to this limitation, JERBY teaches that the checkpoint inhibitor can comprise an anti-PD-L1 [0015].
Claim 29 recites the limitation wherein said checkpoint inhibitor comprises Enoblituzumab, Ipilimumab, Tremelimumab, Lirilumab, BMS986016, Pembrolizumab, Nivolumab, Pidilizumab, Atezolizumab, BMS-936559, Durvalumab, Avelumab, Bavituximab, or a combination thereof. With respect to this limitation, JERBY teaches that the checkpoint inhibitor can include at least Ipilimumab, Nivolumab, Pembrolizumab, and Atezolizumab [0340].
Claim 30 recites the limitation wherein said immunotherapy regimen is identified based at least on the ratio of activated:exhausted T-cells in said sample. With respect to this limitation, JERBY teaches determining the balance (ratio) of exhaustion to cytotoxicity signatures/states [092, 418].
Claim 31 recite the limitation wherein said immunotherapy regimen is identified based at least on an elevated level of exhausted T-cells in said sample. With respect to this limitation, JERBY teaches that immunotherapy effectiveness can be identified by an elevated level of exhausted T-cells and how it can impact the number of exhausted or dysfunctional CD8+ T-cells [0262, 0271, 393].
Claim 32 recites the limitation wherein said sequencing data comprises expression levels of one or more immune modulatory genes. With respect to this limitation, JERBY teaches determining expression levels of immune modulation genes [0403, 515].
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 Rejection over Patent No. 11742058
Claims 13-14, 18, and 20-29 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9-11 and 13-14 of U.S. Patent No. 11742058. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the present application are anticipated by the claims of the patent:
Claims 13-14, 18 and 27 of the present application is anticipated by claim 1 of patent No. 11742058.
Claim 20 of the present application is anticipated by claim 2 of patent No. 11742058.
Claims 21-24 of the present application is anticipated by claims 3-6 and 9 of patent No. 11742058.
Claim 25 of the present application is anticipated by claim 13 of patent No. 11742058.
Claim 26 of the present application is anticipated by claim 14 of patent No. 11742058.
Claim 28 of the present application is anticipated by claim 10 of patent No. 11742058.
Claim 29 of the present application is anticipated by claim 11 of patent No. 11742058.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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/MARY C LEVERETT/ Examiner, Art Unit 1687
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