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 .
Receipt is acknowledged of IDS filed on 07/23/2025.
Claims 36 have been added.
Claims 2, 18, and 32 have been amended.
Claims 2, 3, 9-11, 14-16, 18, 19, 23, 25, 29, 32, and 36 are pending.
Claims 1, 4-8, 12-13, 17, 20-22, 24, 26-28, 30-31, and 33-35 are cancelled.
Claims 16, 25, and 29 are withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 2, 3, 11, 14, 15, 18, 19, 23, 32 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over EDER (WO 2015/055318) in view of EASTON (An unexpected success for cancer immunotherapy treating prostate cancer. U Chicago Medicine. 2018.).
EDER teaches using following compound, which is formula Ia in the instant claims, for treating prostate cancer (claim 10):
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(claim 3). The compound is further radiolabeled with 177Lu (claim 6) and is administered into a patient (Page 4, figure 2). EDER further teaches that the composition can be given in combination with other therapies to provide a therapeutic benefit (Page 21, paragraph 5). EDER teaches that the radiopharmaceutical described should have a sufficient enough concentration to provide satisfactory imaging (Page 23, paragraph 2).
EDER does not teach administering an I-O therapeutic agent, such as the PD-1 inhibitor nivolumab.
EASTON teaches a method of treating prostate cancer using PD-1 inhibitors, such as nivolumab, which can restore the ability of T cells to penetrate and attack tumors (Page 2, paragraph 7).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate nivolumab. The person of ordinary skill in the art would have been motivated to make those modifications, because both have been shown to have a therapeutic activity against the same disease, prostate cancer, and would have an additive effect and reasonably would have expected success because both references are the same field of endeavor, such as therapeutics for prostate cancer and EDER teaches that the compound can be given in combination with other therapies used for the same disease.
The reference does not specifically teach amount of the radiolabeled compound administered as claimed by the Applicant. The amount of the radiolabeled compound administered is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal amount of the radiolabeled compound administered in order to best achieve desired results, such as providing satisfactory imaging. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the amount of the radiolabeled compound administered would have been obvious at the time of Applicant’s invention.
Claims 2, 3, 9-11, 14, 15, 18, 19, 23, 32 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over EDER (WO 2015/055318) and EASTON (An unexpected success for cancer immunotherapy treating prostate cancer. U Chicago Medicine. 2018.) in view of PRIFTAKIS (Neuroendocrine differentiation in castration-resistant prostate cancer: A case report. Molecular and Clinical Oncology. 2015.)
EDER and EASTON teach Applicant’s invention as discussed above.
EDER and EASTON do not teach adding octreotide.
PRIFTAKIS teaches that octreotide is used to treat prostate cancer (abstract) and can be radiolabeled. It further teaches that it can be used in combination with other drugs (abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate octreotide. The person of ordinary skill in the art would have been motivated to make those modifications, because it has been shown to treat prostate cancer and would have an additive effect, and reasonably would have expected success because both EDER and PRIFTAKIS teach that the therapeutics listed can be given in combination with other therapies used for the same disease.
Response to Arguments
Applicant argues, according to the Office Action, Eder discloses a compound of Formula Ia for treating prostate cancer. Applicant indicates that the Office Action intended to refer to the second compound recited in claim 3 of Eder (p. 42), instead of the eighth compound (MB24) recited in claim 3 of Eder (p. 46), as reading on a compound of Formula Ia. The Office Action asserts that Eder discloses the composition can be given in combination with other therapies to provide a therapeutic benefit. (See, Office Action, p. 4, citing Eder, p. 21, fifth paragraph). Although Eder broadly discloses that the definition of an effective amount of a compound refers to the "amount of therapeutic alone, or in combination with other therapies, to provide a therapeutic benefit," Eder does not explicitly disclose a combination of a compound of Formula Ia with an additional therapy. (See, Eder, p. 21, 11. 28-31). To cure this deficiency, the Office Action turns to Easton. According to the Office Action, Easton discloses a method of treating prostate cancer using PD-1 inhibitors, such as nivolumab, which can restore the ability of T cells to penetrate and attack tumors. (See, Office Action, p. 4, citing Easton, p. 2, 7th paragraph).
The Office Action reasons that it would have been obvious to administer both the compound in Eder and nivolumab on the grounds that the person of ordinary skill in the art would have been motivated to make those modifications, and reasonably would have expected success because both are functional equivalents of treatments for prostate cancer. Office Action, p. 4. The Office Action contends that the compound in Eder and nivolumab have been shown to have a therapeutic activity against the same disease, prostate cancer, and that Eder teaches that the compound can be given in combination with other therapies used for the same disease. Applicant respectfully disagrees with the analysis and resulting conclusions in view of the amendments to the claims herein and the remarks below.
Easton discloses the use of a combination of two specific immunotherapies, ipilimumab ( a
CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor) in the treatment of a patient with end-stage
prostate cancer. According to Easton, immunotherapy has not demonstrated success in large
subsets of patients with different types of cancer, such as in the treatment of advanced prostate
cancer. (See, Easton, p. 2, 10th-11th paragraph). Easton further discloses that therapy using ipilimumab or nivolumab separately for end-stage prostate cancer "fell short" (i.e., was not effective). (See, Easton, p. 2, 10th paragraph). Thus, Easton teaches that nivolumab alone was not effective in the treatment of advanced prostate cancer. Easton only discloses the use of nivolumab m combination with one specific immunotherapeutic agent, and fails to provide any teaching or suggestion of the combination of nivolumab with any other therapeutic. Further, Easton attributes the efficacy of the immunotherapy combination of ipilimumab and nivolumab to be a result of nivolumab compensating/or a particular disadvantage associated with the use of ipilimumab. (See, Easton, p. 2, 13th paragraph). In particular, Easton discloses that ipilimumab can trigger increased PD-1 activity, which prevents T cells from mounting the desired anti-tumor response; however, nivolumab targets the PD-1 pathway, which can potentially enhance the T cell attack on the tumor. (See, id.). Thus, the efficacy of the combination immunotherapy is solely attributed to the particular combination of ipilimumab and nivolumab. The references cited in the Office Action do not demonstrate that a compound of Formula Ia would behave in a similar manner to ipilimumab such that co-treatment with nivolumab would be beneficial. Therefore, the person of ordinary skill in the art, considering the teachings of Easton, would not have reasonably expected that the combination of a compound of Formula Ia, a radiolabeled therapeutic that is fundamentally different from ipilimumab (a CTLA-4 inhibitor), and a PD-1 inhibitor (e.g., nivolumab) would behave similarly to the immunotherapy combination of ipilimumab and nivolumab, or would have provided any similar therapeutic effect. Moreover, it is respectfully asserted that the combined use of both a compound of Formula Ia and a PD-1 inhibitor recited in the amended claims provides for an improved therapy for the treatment of PSMA expressing cancer. The effect is supported by the Description in the application as filed (p. 4, 11. 26-31), and has been confirmed by first clinical trial data shown in the post-published study submitted herewith (Sandhu, et al.). The combined use of a compound of Formula Ia with a PD-1 inhibitor was safe and had surprisingly encouraging preliminary activity in patients with metastatic castration-resistant prostate cancer. These results would not have been reasonably predicted based on the alleged combination of prior art and the unpredictability present in the art. For example, Easton recognizes the unpredictability in drug discovery by disclosing that cancer is "a complex problem, with a tangle of pathways that are unique to each patient" and that multiple local factors, such as tumor-microenvironment, play a role in treatment efficacy. (See, Easton, p. 2, 15th , paragraph).
Examiner does not find the argument persuasive because in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, EDER teaches using following compound, which is formula Ia in the instant claims, for treating prostate cancer (claim 10):
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(claim 3). The compound is further radiolabeled with 177Lu (claim 6) and is administered into a patient (Page 4, figure 2). EDER further teaches that the composition can be given in combination with other therapies to provide a therapeutic benefit (Page 21, paragraph 5). EDER teaches that the radiopharmaceutical described should have a sufficient enough concentration to provide satisfactory imaging (Page 23, paragraph 2).
EDER does not teach administering an I-O therapeutic agent, such as the PD-1 inhibitor nivolumab.
EASTON teaches a method of treating prostate cancer using PD-1 inhibitors, such as nivolumab, which can restore the ability of T cells to penetrate and attack tumors (Page 2, paragraph 7).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate nivolumab. The person of ordinary skill in the art would have been motivated to make those modifications, because both have been shown to have a therapeutic activity against the same disease, prostate cancer, and would have an additive effect and reasonably would have expected success because both references are the same field of endeavor, such as therapeutics for prostate cancer and EDER teaches that the compound can be given in combination with other therapies used for the same disease.
Conclusion
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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618