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 4/13/26 with the following:
Amended claims
1, 15, 33
Newly canceled claims
10-13, 23-26
Newly added claims
Previously canceled claims
4-7, 20-22, 28-31
Previously withdrawn claims
Claims under instant examination
1-3, 8-9, 14-19, 27, 32-33
Terminal Disclaimer
The terminal disclaimer filed on 4/13/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent Application 19/170,388 and 18/835,9413 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Claim Rejections
All rejections pertaining to claims 10-13 and 23-26 are moot because the claims were cancelled in view of the amendments filed on 4/13/26.
The provisional rejection of
claims 1-3, 8-19, 23-27 and 32-33 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-30 of copending Application No. 19/170,388; and
claims 1-3, 8-19, 23-27 and 32-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of copending Application No. 18/835,913 in view of Kmiec (US 2020/0370047; published: 11/26/20; in IDS dated 6/17/25)
are hereby withdrawn in view of the Terminal Disclaimer filed on 4/13/26.
Modified and Maintained Claim Rejections - 35 USC § 102/103
Applicant' s claim amendments have necessitated the following modified grounds of rejection.
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.
Claims 1-3, 8-9, 14-19, 23 and 32-33 remain rejected 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).
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].
Therefore, by teaching all the limitations of claims 1-3, 8-9, 14-19, 23 and 32-33, Kmiec anticipates the instant invention as claimed.
Alternatively, with regards to the claims 1 and 15 administration limitation of “intratumorally”, Kmiec teaches that the nucleic acid sequences can be delivered to an appropriate cell of a subject, e.g., a cancer cell [0092]. It is clear that the administration 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. Based on these 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.
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 effective filing date of the claimed invention, 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 have been fully considered, but are not found persuasive.
With regards to the 102 rejections, Applicants argue that Kmiec et al. does not disclose intratumoral administration, either explicitly or implicitly (Remarks: p. 7).
This is not found persuasive. In response, the Examiner directs attention to MPEP 2131.02(III) which states: “A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure”. In the instant rejection, Kmiec teaches wherein the abovementioned composition can be delivered to a cancer cell and wherein the cancer can be a solid tumor. Furthermore, Kmiec teaches multiple routes of administration such as pulmonary, topically (e.g., rectal), ocularly, orally and parenterally. Example of possible intratumoral administration within the teachings of Kmiec, is topical administration to rectum or skin for treating solid tumors (e.g., rectal cancer or skin cancer) or oral administration to treat solid tumors (e.g., mouth or oral cancers). As known by one of ordinary skill in the art, there are two main ways to administer drugs to cancer cells: systemic delivery or targeted delivery, wherein there are subspecies of targeted delivery which includes direct tumor injection. An important factor for indicating that a species is “at once envisaged” from the generic disclosure is emphasized in in Osram Sylvania Inc. v. American Induction Tech. Inc., 701 F.3d 698, 706, 105 USPQ2d 1368, 1374 (Fed. Cir. 2012) which states: “how one of ordinary skill in the art would understand the relative size of a genus or species in a particular technology is of critical importance” (see MPEP 2131.02(III)). As described above there are two main species of routes of administration to deliver a drug/active to a cancer cell and within the targeted delivery species, there are a relatively small number of subspecies (e.g., nanocarriers, active targeting via targeting moiety, stimuli-response release (pH, enzymes, magnet) and direct tumor injection (i.e., intratumoral). Therefore, the Examiner maintains that one of ordinary skill in the art would understand that intratumoral is one of a few options to deliver the composition of Kmiec to a cancer cell and therefore the generic disclosure of Kmiec anticipated the claimed species (intratumoral administration) as such can be “at once envisaged” from the disclosure.
With regards to the 103 rejection, Applicants argue that Kmiec et al. does not teach or suggest delivery of CRISPR/Cas systems to solid tumors through an intratumoral method using an LNP complex or in a viral vector selected from adenovirus, AAV and helper-dependent adenovirus (Remarks: p. 8).
This is not found persuasive. In response, and as indicated in the instant 103 rejection, Kmiec teaches a pharmaceutical composition comprising CRISPR/Cas system used to treat cancer, wherein the cancer is a solid tumor and wherein treating is carried out by administering the composition to the cancer cell (see rejection for detailed teachings and cited locations in the prior art). Kmiec teaches multiple routes of administration such as pulmonary, topically (e.g., rectal), ocularly, orally and parenterally. Example of possible intratumoral administration within the teachings of Kmiec, is topical administration to rectum or skin for treating solid tumors (e.g., rectal cancer or skin cancer) or oral administration to treat solid tumors (e.g., mouth or oral cancers). As described above, there are a finite number of predictable solutions to deliver the composition to the cancer cell, one of which is intratumoral administration. Therefore, the Examiner maintains that the instant 103 rejection is proper in that one of ordinary skill in the art would choose from a finite number of identified, predictable solutions, with a reasonable expectation of success (see MPEP 2143 (I)(E)).
Applicants argue that the instant specification states “there are at least three main reasons around such discouragement of intratumoral therapy: the tumor can be resected and therefore direct treatment is unnecessary, a direct injection will stimulate metastases, and local targeting provides no benefit in dealing with metastases” [0001]. (Remarks: p. 8).
This is not found persuasive. In response, it is first noted, that it appears that Applicants are arguing that there is a teaching away for using intratumoral administration. However, the Examiner directs attention to MPEP 2144.05(III)(B), which states: “A prima facie case of obviousness may also be rebutted by showing that the art, in any material respect, teaches away from the claimed invention.” (emphasis added). The Examiner adds that not all tumors can be surgically removed and such presents risks as well; as one of ordinary skill in the art knows, intratumoral injections goal is to decrease/eliminate metastases; and there are other goals of treating cancer such as that taught by Kmiec: 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].
Conclusion
THIS ACTION IS MADE FINAL. 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 GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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/GENEVIEVE S ALLEY/ Primary Examiner, Art Unit 1617
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