NOTE: The examiner for this application has changed. The new examiner is Sean Aeder.
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/Restriction
The response filed on 9/30/25 to the restriction requirement of 7/30/25 has been received. Without traverse, Applicant has elected the following species: (I) measurement of a biomarker, (II) HSP70, (III) protein analysis, and (IV) melanoma.
Claims 1-20 are pending and are currently under consideration.
Claim Rejections - 35 USC § 102
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) 1-3, 5-12, and 15-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hanks et al (US 2019/0316208 A1; 10/17/19; 12/30/24 IDS).
Hanks et al teaches a method comprising obtaining a biological sample derived from a subject with cancer, determining the level of HSP70 in the sample, comprising the level of HSP70 to a control, classifying the subject as having immunotherapy resistant cancer when the level of HSP70 in the sample is great than that of the control, and administering an anti-wnt-b-catenin signaling pathway inhibitor and an anti-wnt-b-catenin-mediated immunotherapy to the subject with immunotherapy resistant cancer (claim 21 and [0011]-[0012], in particular). Hanks et al further teaches said method wherein the cancer is melanoma ([0016], in particular). Hanks et al further teaches said method wherein the anti-wnt-b-catenin signaling pathway inhibitors are various anti-cancer agents other than immunotherapy ([0077]-[0079], in particular). As defined by instant claim 6, a marker of activation of the NLRP3-HSP70 axis comprises NLRP3. Hanks et al further teaches said method wherein the level of HSP70 is detected by a technique such as ELISA ([0084], in particular). Hanks et al further teaches said method wherein the sample is plasma ([0015], in particular). Hanks et al further teaches said method wherein the anti-wnt-b-catenin-mediated immunotherapy is anti-PD1 immunotherapy, such as pembrolizumab ([0013] and [0075], in particular). Hanks et al further teaches said method wherein the sample is taken 12 weeks after commencing anti-PD1 immunotherapy and the control is a sample taken prior to immunotherapy and that an increase in the sample after commencing immunotherapy (as compared to a corresponding control) is indicative of non-responsiveness to anti-PD1 immunotherapy (Figure 21B, in particular).
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.
Claims 1-3, 5-17, 19, and 20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Theivanthiran et al (JCI, 2020, 130(5): 2570-2586; 12/30/24 IDS).
Theivanthiran et al teaches plasma HSP70 protein levels, detected by ELISA, increased 12 after beginning anti-PD-1 blockade immunotherapy (as compared to baseline levels before treatment) in advanced melanoma patients undergoing anti-PD-1 immunotherapy that exhibit disease progression and the increase in HSP70 levels was seldomly observed in melanoma patients that respond to the anti-PD-1 immunotherapy (Figure 7 and first full paragraph of the right column on page 2579, in particular). Theivanthiran et al further describes the changes in plasma HSP70 levels with anti-PD-1 antibody therapy as “significantly greater” in non-responding melanoma patients relative to responders (Figure 7G and first full paragraph of the right column on page 2579, in particular). Theivanthiran et al further describes NLRP3 and HSP70 as markers of an NLRP3-HSP70 axis (Figure 1A, in particular). Theivanthiran et al further teaches inhibition of NLRP3 with the MCC950 small molecule enhances efficacy of anti-PD-1 immunotherapy in melanoma patients (Figure 6, in particular).
Theivanthiran et al does not specifically teach a method comprising classifying a subject for likelihood of clinical response to anti-PD-1 immunotherapy based on levels of HSP70. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to determine whether subjects with advanced melanoma are responsive to anti-PD-1 blockade immunotherapy of Theivanthiran et al comprising obtaining baseline (“control”) plasma samples from the subjects before any therapy, administering the anti-PD-1 immunotherapy of Theivanthiran et al to the subjects, obtaining plasma sample from the subjects 12 days after the therapy begins, detecting levels of HSP70 protein in the samples by ELISA, classifying subjects with increased HSP70 protein levels in the samples after the anti-PD-1 immunotherapy began (as compared to baseline samples) as subjects that are more likely non-responsive to the anti-PD-1 immunotherapy, and classifying subjects with levels of HSP70 protein in the samples after the anti-PD-1 immunotherapy began equal to or lower than those in baseline samples as subjects that are more likely responsive to the anti-PD-1 immunotherapy because Theivanthiran et al teaches plasma HSP70 protein levels (detected by ELISA) increased 12 after beginning anti-PD-1 immunotherapy (as compared to baseline levels before treatment) in advanced melanoma patients undergoing anti-PD-1 immunotherapy that exhibit disease progression and the increase in HSP70 levels was seldomly observed in melanoma patients that respond to the anti-PD-1 immunotherapy (Figure 7 and first full paragraph of the right column on page 2579, in particular). Theivanthiran et al further describes the changes in plasma HSP70 levels with anti-PD-1 antibody therapy as “significantly greater” in non-responding melanoma patients relative to responders (Figure 7G and first full paragraph of the right column on page 2579, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said method wherein subjects determined more likely to respond to anti-PD-1 immunotherapy are administered additional anti-PD-1 immunotherapy in an effort to obtain further therapeutic benefit from an agent the subjects more likely therapeutically respond to. Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said method wherein subjects administered additional anti-PD-1 immunotherapy are further administered an NLRP3 small molecule inhibitor because Theivanthiran et al teaches inhibition of NLRP3 with the MCC950 small molecule enhances efficacy of anti-PD-1 immunotherapy in melanoma patients.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said method wherein subjects determined more likely non-responsive to the anti-PD-1 immunotherapy discontinue the anti-PD-1 immunotherapy and are administered an anti-melanoma treatment other than the anti-PD-1 immunotherapy in an effort to obtain therapeutic benefit from an alternative melanoma therapy.
This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-3 and 5-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Theivanthiran et al (JCI, 2020, 130(5): 2570-2586; 12/30/24 IDS) as applied to claims 1-3, 5-17, 19, and 20 above, and further in view of NCT02694965 clinical trial (08/07/2020 record at Record History | ver. 7: 2020-08-07 | NCT02694965 | ClinicalTrials.gov).
Teachings of Theivanthiran et al are discussed above. Theivanthiran et al further teaches the subjects with advanced melanoma of Theivanthiran et al are in the NCT02694965 clinical trial (right column on page 2582, in particular).
Theivanthiran et al does not specifically teach the subjects with advanced melanoma of Theivanthiran et al from the NCT02694965 clinical trial are stage III or IV. However, these deficiencies are made up in the teachings of NCT02694965.
NCT02694965 teaches the melanoma patients of NCT02694965 clinical trial are stage III or IV (see “Groups/Cohorts”).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of determining whether subjects with advanced melanoma are responsive to anti-PD-1 immunotherapy rendered obvious by Theivanthiran et al wherein the subjects with advanced melanoma are stage III or IV because Theivanthiran et al teaches plasma HSP70 protein levels (detected by ELISA) increased 12 after beginning anti-PD-1 immunotherapy (as compared to baseline levels before treatment) in advanced melanoma patients that are stage III or IV (as evidenced by NCT02694965) undergoing anti-PD-1 immunotherapy that exhibit disease progression and the increase in HSP70 levels was seldomly observed in melanoma patients that respond to the anti-PD-1 immunotherapy. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Theivanthiran et al (JCI, 2020, 130(5): 2570-2586; 12/30/24 IDS) as applied to claims 1-3, 5-17, 19, and 20 above, and further in view of Colle et al (Journal of Clinical Oncology, 2019, 37(15 supp): Abstract e21021).
Teachings of Theivanthiran et al are discussed above.
Theivanthiran et al does not specifically teach evaluating the subjects for development of disease hyperprogression or that the subjects with advanced melanoma of Theivanthiran et al from the NCT02694965 clinical trial are stage III or IV. However, these deficiencies are made up in the teachings of Colle et al.
Colle et al evaluating stage III and IV melanoma patients treated with anti-PD-1 blockade immunotherapy for development of disease hyperprogression and found 41% of patients with hyperprogression died within 3 months (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of determining whether subjects with advanced melanoma are responsive to anti-PD-1 immunotherapy rendered obvious by Theivanthiran et al wherein the subjects with advanced melanoma are stage III or IV and are evaluated for hyperprogression in an effort to provide the subjects a prognosis because Colle et al evaluating stage III and IV melanoma patients treated with anti-PD-1 blockade immunotherapy for development of disease hyperprogression and found 41% of patients with hyperprogression died within 3 months. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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 1-3 and 5-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-14 of U.S. Patent No. 11643691 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims are directed to species of the instant claims.
Claims 1-14 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-14 of U.S. Patent No. 11643691 B2 in view of Theivanthiran et al (JCI, 2020, 130(5): 2570-2586; 12/30/24 IDS) and Colle et al (Journal of Clinical Oncology, 2019, 37(15 supp): Abstract e21021). The patent claims are directed to species of instant claims 1-3 and 5-12. Regarding instant claims 4 and 18, it would be obvious to evaluate the subject administered the anti-PD-1 immunotherapy of the patent method when the subject is has stage III or IV melanoma for disease hyperprogression in an effort to provide a prognosis because Colle et al evaluating stage III and IV melanoma patients treated with anti-PD-1 blockade immunotherapy for development of disease hyperprogression and found 41% of patients with hyperprogression died within 3 months (Abstract, in particular). Regarding instant claims 13-14, it would be obvious to administer the NLRP3 small molecule inhibitor of Theivanthiran et al when administering the anti-PD-1 immunotherapy to subjects with melanoma of the patented method because Theivanthiran et al teaches inhibition of NLRP3 with the MCC950 small molecule enhances efficacy of anti-PD-1 immunotherapy in melanoma patients (Figure 6, in particular).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN E AEDER/ Primary Examiner, Art Unit 1642