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 .
Specification
The use of the terms Synta66 (para. 12, 17), Zegocractin (para. 17, 18), Tween (para. 21), and Pluronics (para.21), which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
Claim 2 is 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.
Claim 2 is indefinite because it depends from itself. As a consequence, its metes and bounds are indeterminate, which renders this claim ambiguous. Further dependent claims 3-7 will not at this time be considered on the merits due to their dependencies on claim 2. Assuming the future amendment of claim 2, treatment of the dependent claims has been included below.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable by Chakraborty et al. (ML28 HCl is more efficient than capsaicin in inhibiting bacterial antigen-induced cal 27 oral cancer cell proliferation, International Journal of Molecular Sciences, 2021, 22, 22, 12559). Chakraborty discloses the use of a T-type calcium channel blocker, ML218 HCl, in attenuating oral squamous cell carcinoma, Cal27, proliferation, cell viability, and metabolism under LPS stimulation (abstract).
Chakraborty does not, however, disclose the administration of the calcium channel blocker to an individual who has oral cancer.
Schoenfeld (Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma, JAMA Oncology, 2020, 6, 10, 1563-1570) teaches a pharmacological approach to treating oral squamous cell carcinoma prior to surgery in a phase 2 clinical trial using PD-1 and CTLA-4 checkpoint inhibitors, observing promising rates of response, some toxic effects, and a 1-year progression-free survival of 85% (abstract).
As such, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to apply a similar therapeutic approach with calcium channel blockers as described by Chakraborty.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Chakraborty and Schoenfeld as applied to claim 1 above, and further in view of Jardin (STIM and calcium channel complexes in cancer, Biochimica et Biophysica Acta, 2016, 1863, 1418-1426).
Chakraborty discloses:
the use of a T-type calcium channel blocker, ML218 HCl, in attenuating oral squamous cell carcinoma, Cal27, in terms of proliferation, cell viability, and metabolism after LPS stimulation.
Schoenfeld discloses:
clinical application of pharmacological therapy to oral squamous cell carcinoma and the promising outcomes to patients involved.
Chakraborty and Schoenfeld do not disclose the use of specific ORAI Ca2+ channels.
Jardin discloses:
dysfunction of mechanisms involving in calcium homeostasis driving pathological processes including cancer, and further illustrates store-operated calcium entry as a privileged mechanism, including store-operated calcium channel ORAI1, which is mediated by the endoplasmic reticulum, can be selectively targeted, and plays an important role in cell cycle progression and proliferation, migration, metastasis, and evasion of apoptosis (abstract).
As such, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to apply the same therapeutic approach on T-type calcium channels of Chakraborty with ORAI1 calcium channels as described by Jardin, being cognizant of calcium channels’ ubiquitous nature, and the target selective approach store-operated calcium channels provide.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Chakraborty, Schoenfeld and Jardin as applied to claim 2 above, and further in view of Tsujikawa (Regulation of neuropathic pain by microglial Orai1 channels, Science Advances, 2023, 9, eade7002).
Jardin discloses:
the role of ORAI1 channels in calcium driven pathological processes, including cancers.
Jardin does not disclose the use of calcium channel blockers including a group consisting of Synta66, BTP-2, CM-2489, CM-4620, GSK-5498A, GSK-7975A, a combination thereof, and a specific use of CM-4620.
This deficiency is cured by the teachings of Tsujikawa, which discloses:
The use of store-operated calcium entry blocker CM-4620 targeting the ORAI1 membrane channel in attenuating neuroinflammation, calcium signaling and production of inflammatory cytokines, along with pain mitigation in male mice, which was not observed in the ORAI1 knockout cases. This pain reduction was demonstrated only during treatment and pain reemerged upon cessation of the CM-4620 regimen. As such, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to select CM-4620, as described by Tsujikawa, to target oral cancers, including squamous cell carcinoma, as previously disclosed by Chakraborty, as an ORAI1 antagonist, to realize the anti-cancer proliferation effects and the accompanying allodynia reduction.
Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Chakraborty, Schoenfeld, Jardin, and Tsujikawa as the limitations of claim 5-7 are inherently met. Claim 5, depending on claim 3, further limits the claims by administration of the calcium channel blocker that inhibits growth of oral cancer, which is rejected in view of Chakraborty, or inhibits development of allodynia in the individual, in view of Tsujikawa. Claim 6, depending on claim 5, further limits the claims by the method inhibiting growth of oral cancer comprising inhibiting transformation of oral keratinocytes to a squamous cell carcinoma. This is also rejected in view of Chakraborty. Claim 7, depending on claim 5, further limits the claims by administration of the calcium channel blocker to inhibit the development of allodynia in the individual, which is rejected by Tsujikawa in the attenuation of pain by CM-4620 in view of Schoenfeld in treatment of oral squamous cell carcinoma in clinical patients.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622