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 .
Status of Claims
A new claim set was filed on 8/17/26 with the following:
Amended claims
1 and 15
Newly canceled claims
Newly added claims
Previously canceled claims
4-7, 10-13, 20-26 and 28-31
Previously withdrawn claims
Claims under instant examination
1-3, 8-9, 14-19,27 and 32-33
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/17/26 has been entered.
Withdrawn Claim Rejections
The rejections of claims 1-3, 8-9, 14-19, 23 and 32-33 under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Kmiec (US 2020/0370047; published: 11/26/20; in IDS dated 6/17/25) are hereby withdrawn in response to the Applicants amendments/arguments filed on 8/17/26.
New 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3, 8-9, 14-19, 23 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Kmiec (US 2020/0370047; published: 11/26/20; in IDS dated 6/17/25), in view of Jaskula-Ranga et al. (US 2020/0069818; published: 03/05/20).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Kmiec is directed to gene knockout of nrf2 for treatment of cancer (Title).
With regards to independent claims 1 and 15, Kmiec teaches a method of treating cancer comprising administering a pharmaceutical composition comprising: a DNA sequence encoding a guide RNA that is complementary to a target domain from an NRF2 gene in the subject; and a nucleic acid sequence encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease [Abstract]. Kmiec teaches that in certain embodiments, the cancer is a solid tumor [0054]. Kmiec teaches that the pharmaceutical composition is administered in an amount sufficient to reduce tumor growth relative to a tumor that is not treated with the pharmaceutical composition, wherein the reduction in tumor growth is at least, for example by 20% [0105]. Kmiec also teaches a method of reducing NRF2 expression or activity in a cell comprising introducing into the cell (a) one or more DNA sequence(s) encoding a guide RNA (gRNA) that is complementary to a target sequence in the NRF2 gene and (b) a nucleic acid sequence encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, whereby the gRNA hybridizes to the NRF2 gene and the CRISPR-associated endonuclease cleaves the NRF2 gene, and wherein NRF2 expression or activity is reduced in the cell relative to a cell in which the one or more DNA sequences encoding the gRNA and the nucleic acid sequence encoding the CRISPR-associated nuclease are not introduced [0096]. With regards to the claimed administration, Kmiec teaches that the nucleic acid sequences can be delivered to an appropriate cell of a subject, e.g., a cancer cell [0092]. When one of ordinary skill in the art might be able to envisage the claimed species from a prior art reference that discloses a genus with a limited number of species, but does not specifically disclose by name the claimed species, the examiner may be able to justify a rejection under 35 U.S.C. § 102. MPEP 2131.02(III) and 2144.08; See: In re Schaumann, 197 USPQ 5 (CCPA 1978). With regards to CRISPR/Cas system, Kmiec teaches that a vector can comprise the aforementioned DNA sequence, wherein the vector is an adeno-associated virus (AAV) vector, wherein the vector comprises a nucleic acid sequence that encodes a CRISPR-associated endonuclease protein such as Cas9 or Cas12a [0016, 0083, 0084]. Kmiec also teaches that the viral vector is adenovirus or helper-dependent adenovirus [0084]. It is noted that Kmiec teaches wherein two or more elements expressed from the same or different regulatory elements may be combined in a single vector or separate vectors [0050].
With regards to instant claims 2-3 and 16-17, Kmiec teaches wherein the one or more gRNAs comprise a trans-activated small RNA (tracrRNA) and a CRISPR RNA (crRNA) and in other embodiments, the one or more gRNAs are one or more single guide RNAs [0006].
With regards to instant claims 8-9, and 18-19, Kmiec teaches that in some embodiments, the CRISPR-associated endonuclease is a class 2 CRISPR-associated endonuclease, and in some embodiments, the class 2 CRISPR-associated endonuclease is Cas9 or Cas12a [0006].
With regards to instant claims 14 and 27, Kmiec teaches wherein the compositions are used for treatment of various types of solid tumors, or example breast cancer, bladder cancer, colon and rectal cancer, endometrial cancer, kidney (renal cell) cancer, lung cancer, melanoma, pancreatic cancer, prostate cancer, thyroid cancer, skin cancer, bone cancer, brain cancer, cervical cancer, liver cancer, stomach cancer, mouth and oral cancers, neuroblastoma, testicular cancer, uterine cancer, thyroid cancer, head and neck, kidney, lung, non-small cell lung, melanoma, mesothelioma, ovary, sarcoma, stomach, uterus and medulloblastoma, and vulvar cancer. In certain embodiments, solid tumors include breast cancer, including triple negative breast cancer. In certain embodiments, skin cancer includes melanoma, squamous cell carcinoma, cutaneous T-cell lymphoma (CTCL) [0110].
With regards to instant claims 32-33, Kmiec teaches wherein the method further comprises administering one or more chemotherapeutic agents to the subject [0019].
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Kmiec teaches that the nucleic acid sequences can be delivered to an appropriate cell of a subject, e.g., a cancer cell [0092]; more specifically, Kmiec teaches that in some embodiments, exosomes may be used for delivery of a nucleic acid encoding a CRISPR endonuclease and/or guide RNA to a target cell, e.g., a cancer cell [0086]. Kmiec also teaches that the administration can include pulmonary, topical, ocular, oral or parenteral, wherein parenteral administration includes intravenous, intra-arterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular administration [0090]. However, Kmiec do not specifically teach that the administration is intratumorally by direct injection into the solid tumor, as required by instant claims 1 and 15. However, such deficiency is cured by Jaskula-Ranga.
Jaskula-Ranga is directed to CRISPR/Cas9-based compositions and method for treating cancer [Title and Abstract]. Jaskula-Ranga define “parenteral administration” and “administered parenterally” as a mode of administration other than enteral and topical administration, usually by injection and includes intratumoral injection [0256].
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It is clear that the administration taught by Kmiec of the abovementioned composition to the subject produces a result wherein the active agents are “delivered” to the cancer cell, but Kmiec does not specifically teach that such administration is intratumorally. It is noted that Kmiec discloses multiple routes of administration including pulmonary, topically, ocularly, orally and parenterally and the purpose of the method of Kmiec is to inhibit tumor growth and/or reduce tumor size. Furthermore, Jaskula-Ranga teaches that parenteral administration of similar CRISPR/Cas9-based compositions include intratumoral injections. Based on these combined teachings, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Kmiec by specifically administering its composition intratumorally in order to provide an effective amount of active agents at the site of action (i.e., the tumor).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Response to Arguments
Applicants’ arguments are moot in view of the new grounds of rejection.
Conclusion
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 extension fee 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 GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached on Monday-Friday 8:00-5:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GENEVIEVE S ALLEY/Primary Examiner, Art Unit 1617
