DETAILED ACTION
Status of Claims
The amendment submitted February 25, 2025 has been entered.
Claims 1-21 are pending and under consideration.
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 .
Information Disclosure Statement
An information disclosure statements (IDS) submitted on August 10, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
(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.
Claims 1, 3-5, 15-19, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sánchez (Sánchez, M.G et at., 2005. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. European journal of pharmacology, 515(1-3), pp.20-27).
The Examiner notes Applicant discloses on page 7, paragraph [0046] of the specification that “ The compositions and methods described herein are for use with any subject in whom RTX is effective, e.g., able to bind and activate TRPV-1 or a homolog thereof, and who is in need of treatment for prostate cancer. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a cat. In some embodiments, the mammal is a dog.”
Regarding claim 1, Sánchez teaches “a method of treating prostate cancer, comprising administering resiniferatoxin (RTX) to a subject in need of treatment of prostate cancer.”
Sánchez specifically teaches administration of RTX to human prostate epithelial cell lines LNCaP and PC-3 and in human prostate from three different patients (abstract, “Materials and methods”, page 21, column 1, paragraph 4; page 25, column 1, paragraph 2 and column 2 paragraph 3).
Regarding claim 3, Sánchez teaches “wherein the RTX is administered locally.”
As aforementioned, Sánchez discloses studies where RTX is administered locally to study TRPV1 receptor in prostate cells and prostate tissue (page 22, column 2, paragraph 3).
Regarding claim 4, Sánchez teaches “wherein the RTX is administered peritumorally.”
Sánchez teaches administration of RTX to PC-3 cells, LNCaP cells and prostate tissue from Benign Prostate Hyperplasia patient (page 23, figure 2).
Regarding claim 5, Sánchez teaches “wherein the subject previously underwent prostate surgery,” specifically as studies were conducted using “human prostate tissue obtained from radical prostatectomy of 55-75 year old patients,” (page 23, column 2, paragraph 1 and Figure 1).
Regarding claims 15-16, Sánchez teaches “wherein the subject is a mammal,” and wherein the mammal is a human.
As aforementioned, Sánchez discloses studies using human prostate tissue from patients and human prostate epithelial cell lines LNCaP and PC-3.
Regarding claim 17, Sánchez teaches studies “wherein the prostate cancer is prostate adenocarcinoma.”
Sánchez teaches specifically that “The PC-3 cell line is a human prostatic adenocarcinoma metastatic to bone and is androgen-insensitive (page 23, column 1, lines 3-4).”
Regarding claims 18-19 and 21, Sánchez teaches “wherein the method comprises administering a pharmaceutical formulation comprising the RTX and a pharmaceutically acceptable carrier,” and “wherein the pharmaceutically acceptable carrier comprises water,” and “wherein the pharmaceutically acceptable carrier comprises a buffer.”
Sánchez specifically teaches “Briefly, membrane suspensions (50 Ag of protein) were incubated at 37-C for 60 min with 50 pM [125I] resiniferatoxin (2200 Ci/mmol, Perkin-Elmer, Wesley, MA, USA), in the presence or absence of increasing concentrations of the competitive non-radioactive resiniferatoxin (Sigma, St. Louis, MO, USA), (R)-methanandamide or capsaicin (Tocris, Bristol, UK), in a final volume of 0.25 ml of assay buffer (10 mM HEPES, pH 7.4, 5 mM KCl, 5.8 mMNaCl,0.75 mMCaCl2, 2 mMMgCl2, 320 mM sucrose, 0.25 mg/ml BSA acid free) (page 22, column 1, paragraph 2).”
Therefore, claims 1, 3-5, 15-19 and 21 are rejected as being anticipated by Sánchez.
Claims 1, 3-5, 12-13, 15-19 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pecze (Pecze, L., Jósvay, K., Blum, W., Petrovics, G., Vizler, C., Oláh, Z. and Schwaller, B., 2016. Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1863(8), pp.2054-2064).
Regarding claim 1, Pecze teaches “a method of treating prostate cancer, comprising administering resiniferatoxin (RTX) to a subject in need of treatment of prostate cancer.”
Specifically, Pecze teaches “Here, we examined whether potent agonist-induced overstimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro,” and that “Moreover, long-term monitoring revealed that merely the ectopic expression of TRPV1 stopped cell proliferation and often induced apoptotic processes via strong activation of caspase-3 activity. Our results indicate that specific targeting of TRPV1 function remains a putative strategy for cancer treatment.”
Consequently, Pecze teaches methods for treating prostate cancer via administration or RTX to subjects in need thereof based on Applicant’s definition as aforementioned.
Regarding claims 3-4, Pecze teaches “wherein the RTX is administered locally,” and “wherein the RTX is administered peritumorally.”
Pecze specifically teaches in vitro and in vivo studies using RTX on human prostate carcinoma cell lines and rat prostate glands (page 2055, column 1, paragraph 4) where RTX is administered locally and peritumorally (page 2058, column 2, paragraph 1).
Regarding claim 5, Pecze teaches “wherein the subject previously underwent prostate surgery,” specifically as studies were conducted using “frozen prostate sections of radical prostatecetomy specimens,” (page 2055, column 2, last paragraph).
Regarding claims 12-13, Pecze teaches “wherein RTX is administered in repeated doses,” and “administered daily.”
Pecze specifically teaches in vivo studies using rats where RTX is administered daily for three days (page 2056, column 1, last paragraph and page 2058, column 2, first paragraph).
Regarding claims 15-16, Pecze teaches “wherein the subject is a mammal,” and “wherein the mammal is a human.”
As aforementioned, Pecze’s studies utilize rats which are mammals and additionally human cell lines and human tissue from patients.
Regarding claim 17, Pecze teaches studies “wherein the prostate cancer is prostate adenocarcinoma.”
Pecze specifically performed studies on PC-3 cell line, which is the known cell line in the art for prostate adenocarcinoma.
Regarding claims 18-19 and 21, Pecze teaches “wherein the method comprises administering a pharmaceutical formulation comprising the RTX and a pharmaceutically acceptable carrier,” and “wherein the pharmaceutically acceptable carrier comprises water,” and “wherein the pharmaceutically acceptable carrier comprises a buffer.”
Pecze’s RTX solutions contain ethanol, water, and buffer (page 2055, column 1, last paragraph “2.1 Chemicals).
Therefore, claims 1, 3-5, 12-13, 15-19 and 21 are anticipated by Pecze.
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.
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.
Claims 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Sánchez and Pecze as aforementioned in view of Jones et al. (WO 2019/049112 A1, Information Disclosure Statement, August 10, 2023, Foreign Patent No. 1).
The teachings of Sánchez and Pecze are applied as set forth above.
Sánchez does not explicitly teach the dosing amounts as recited in claims 6-10 and the dosing schedule as per claims 11-14; however, does teach dose-dependence for RTX, which parallels the dose-dependent as ascribed by instant invention (page 13, Example A of Applicant’s specification).
Pecze does not explicitly teach the dosing amounts nor all the dosing schedules; however, Pecze does teach administration to rats and dosing based on body weight (page 2056, column 1, last paragraph), which is standard in the art of pharmacology to optimize based on patient population.
Additionally, as per MPEP 2144.05, II. A: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
Therefore, a person of ordinary skill in the art of oncology would be motivated to optimizing dosing and dosing schedule based on the individual patient to arrive at instant invention. Applicant has not provided any support for the criticality of the ranges claimed, particularly no guidance pertaining how to optimize methods with respect to patient population and factors such as age, body weight, etc.
Regarding claim 20, Jones teaches formulations for a non-alcoholic formulation of RTX (abstract).
Jones specifically teaches various formulations utilizing polysorbate 80 and buffers including phosphate containing buffers (page 4, Table 1) and the preparation of said formulations.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art to have modified the original methods taught by Sánchez and Pecze because Sánchez and Pecze teach methods for treating prostate cancer using RTX, dose-dependent studies and using a buffering solution and because Jones teaches safer non-alcoholic formulations of RTX.
One would have been additionally motivated to optimize the dosing and dosing schedule as part of routine optimization as is standard in oncology to develop an effective treatment plan, and would have been motivated to use Jones formulations using polysorbate 80 and buffer as such RTX formulations are disclosed as safer options for patient administration.
Therefore, a person of ordinary skill in the art would have arrived at the instant methods as a predictable result with a reasonable expectation of success based on the beneficial teachings of Sánchez, Pecze and Jones.
Consequently, claims 1-21 are rejected on grounds of obviousness.
Conclusion
Claims 1-21 are under consideration and are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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