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 the Claims
The preliminary amendment filed 04/05/2024 is acknowledged. Claims 1-10 are amended and claims 11-13 are canceled. No restriction requirement is being imposed. Claims 1-10 and 14 are under examination.
Claim Objections
Claims 1, 7, 10 and 14 are objected to because of the following informalities.
(i) Claim 1 recites “treating NK cells with a peptide having an amino acid sequence of SEQ ID NO: 1”; claim 7 recites “including a peptide consisting of an amino acid sequence of SEQ ID NO: 1” and claim 14 recites “treating NK cells with a peptide consisting of an amino acid sequence of SEQ ID NO: 1”. Since there is only one SEQ ID NO: 1, the phrase should recite “the amino acid sequence of SEQ ID NO: 1”.
(ii) Regarding claim 7, “including a peptide” is usually phrased “comprising a peptide”.
(iii) Regarding claim 10, the phrase “wherein the cancer is overexpressed or overactivated TGF-β” appears to be a typographical error. Presumably “wherein the cancer is characterized by overexpressionoveractivation of
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 5 and 6 are 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 5 recites the limitation “wherein the composition is an anticancer drug…” in line 2. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which claim 5 depends, does not recite a composition, but rather a method of enhancing NK cell activity comprising treating with the peptide set forth in SEQ ID NO: 1. Further, claim 6 recites “wherein the cancer is a solid cancer or a metastatic cancer” in line 2. There is insufficient antecedent basis for this limitation because neither claim 5, from which claim 6 directly depends nor claim 1, from which claim 6 ultimately depends, recites cancer. Rather, they recite a method of enhancing NK cell activity.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods wherein the pharmaceutical composition comprises a peptide set forth in SEQ ID NO: 1 for treating cancer, does not reasonably provide enablement for preventing. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Claim 7 recites administering a pharmaceutical composition for preventing cancer in the alternative. The term “preventing” is generally understood in the art to encompass a total protection from disease or injury. While the skill in the art is high, the level of predictability is low and the nature of preventing cancer is complex. In contrast to the broad scope of the claims, what is provided in the specification is quite narrow. According to the website https://health.clevelandclinic.org/how-to-prevent-cancer (downloaded 08/17/2026) from the Cleveland Clinic, one can reduce one’s risk of cancer, but it is not completely preventable (see 1st paragraph). There are a number of dietary and lifestyle changes to reduce one’s risk of cancer (see Cleveland Clinic website), however, cancer risk is multifactorial; aging, random genetic mutations and hidden environmental exposures increase risk, thereby making total prevention impossible.
The specification teaches that NK cell cytotoxicity was increased in a non-small cell lung cancer cell line model treated with the peptide set forth in SEQ ID NO: 1 or SB431542 (see p. 20, lines 6-9). Further, administration of SEQ ID NO: 1 to this cell line reduced TGF-β in a dose-dependent manner (see p. 21, lines 18-20). In addition, NK cell fratricide activity was “significantly reduced” in NK92 cells by the peptide set forth in SEQ ID NO: 1 or SB431542 (see p. 21, lines 1-4 of the instant specification). Finally, the instant specification discloses that administration of SEQ ID NO: 1 to a mouse model for lung cancer “significantly reduced” nodules compared to the negative control group (see p. 22, lines 5-7, Figure 6). In summary, the guidance in the instant specification presents evidence that SEQ ID NO: 1 may treat cancer, but there is no guidance suggesting it could prevent all cancer from occurring.
The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, the changes which can be made and still maintain activity/utility are unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986). The test of enablement is not whether any experimentation is necessary, but whether, if necessary, it is undue. Due to the large quantity of experimentation necessary to establish a preventive effect on cancer using SEQ ID NO: 1, the state of the art which establishes the unpredictability of cancer prevention, the lack of guidance and working examples directed to the same and the complex nature of the invention, undue experimentation would be required of the skilled artisan to practice and use the claimed invention in its full scope.
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
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.
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Choi (English translation of KR 20130067238 provided by Korean Ministry of Intellectual Property—hereafter Choi 2013) in view of Choi (KR 20170121017—on IDS filed 05/30/2025—English translation provided by Korean Ministry of Intellectual Property—hereafter Choi 2017). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Choi 2013 teach a pharmaceutical composition for inhibiting cancer metastasis, comprising a gene carrier, a cell, or a TXNIP protein containing a gene as an active ingredient (see claims 11-15; paragraphs [0007]; [0035]; [0037] of the translation). Choi 2013 also indicates that TXNIP (also referred to as VDUP1 therein) is an anticancer therapy (see the title of the research project at p. 3 of the translation). Choi 2013 contemplates treating lung cancer, a solid cancer, as well as blood cancer (see claims 12 and 15 of the translation). The second factor to consider is to ascertain the differences between the prior art and the instant claims. Choi 2013 does not teach the peptide fragment of TXNIP consisting of instant SEQ ID NO: 1.
Choi 2017 teach a TXNIP peptide, TN13, consisting of the amino acid sequence GSKKVILDLPLVI, which shares 100% sequence identity with instant SEQ ID NO: 1 and its encoding nucleotide sequence (see paragraph [0101]). It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the teachings of Choi 2013 by substituting the TN13 peptide because Choi 2017 teach that TN13 was capable of increasing leukocyte proliferation in old mice and reduce reactive oxygen species (ROS—see paragraphs [0009]-[0010] of the translation). The person of ordinary skill in the art would have been motivated to use the TN13 peptide because Choi 2013 discloses that ROS is implicated in cancer metastasis (see paragraphs [0006]; [0022]). Further, Choi 2013 teach that the TXNIP “acts as an antioxidant protein that regulates reactive oxygen species in all hematopoietic cells including immune cells” (see paragraph [0119] of the translation). Therefore, the applied prior art references recognized that (1) ROS was implicated in cancer; (2) TXNIP could be used as a pharmaceutical composition to suppress cancer metastasis and (3) the TN13 peptide acts to suppress ROS. In addition, the art demonstrated the equivalency of TXNIP and the TN13 peptide in suppressing ROS. See 2144.05(II)(A):
“‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.’”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art."”)
In summary, the person of ordinary skill in the art would have been motivated to substitute the TXNIP peptide fragment that has equivalent activity for the full length TXNIP because they were art-recognized equivalents. For this reason, as well, the person of ordinary skill in the art could have reasonably expected success.
Regarding the effects of TN13 on natural killer (NK) cells, these effects would have been inherent to the combined teachings of Choi 2013 and Choi 2017 because together they suggest administering TN13 to treat the same patient population, namely, those with cancer. Therefore, the same clinically significant improvements as recited in the claims must occur as a result of administering TN13 to a patient population being treated for cancer. The recitation of the effects of the TN13 on the patient population and their NK cells are part of to the understandings and expectations disclosed in the applied prior art. The method of treatment and the structure of TN13 for carrying out that treatment was part of the disclosure of the combined prior art teachings, so the effects upon the body of the patients and NK cells are inherent. Further, for the record, the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983). See also MPEP 2112.
Thus, the claims do not contribute anything non-obvious over the prior art.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Choi 2013 and Choi 2017 as applied to claims 1-10 above, and further in view of Choi et al. (WO2006132448—hereafter the ‘448 document) and Copik et al. (US 20180125888). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The combined teachings of Choi 2013 and Choi 2017 and how they meet the limitations of claims 1-10 are outlined above in the preceding rejection and are hereby incorporated. The second factor to consider is to ascertain the differences between the prior art and the instant claims. The combined teachings of Choi 2013 and Choi 2017 do not teach the combined steps of (a) treating NK cells with a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a polynucleotide encoding the peptide; and (b) administering the NK cells of step (a) to a subject.
The ‘448 document teaches a method of increasing natural killer (NK) cell cytotoxicity comprising administering VDUP1 (Vitamin D3 upregulating protein 1, also known as TXNIP) or a gene encoding the protein (see claim 18 and paragraph [29]). The ‘448 document describes VDUP1 as an agent for NK cell differentiation (see claim 1). Choi et al. teach at paragraphs [48] and [49]:
The defective differentiation and activation of NK cells result in a variety of cancers including breast cancer, melanoma and lung cancer. Therefore, an agent for regulating NK cell differentiation of the present invention can be used for the treatment of cancers by regulating NK cell differentiation.
The agent for regulating cell differentiation of the present invention can be administered orally or parenterally and be used in general forms of pharmaceutical formulation. (Citations omitted by examiner).
The ‘448 document discloses VDUP1 may be used to treat “breast cancer, melanoma, stomach cancer and lung cancer” (see paragraphs [18]-[20]), which are solid cancers. The ‘448 document does not explicitly teach administering the NK cells to the subject. It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that NK cells could be treated ex vivo with VDUP1 and administered to the patient to treat cancer because the ‘448 document teaches VDUP1 is necessary for NK cell differentiation (see above) and Copik et al. disclose a method of pre-activating NK cells with stimulatory cytokines ex vivo and infusing patients with said NK cells to treat various types of solid and blood cancers (see paragraph [0034] and claims 1-6). The person of ordinary skill in the art would have been motivated to transplant NK cells treated with VDUP1 (i.e. TXNIP) to cancer patients because Copik teaches:
Infusions of NK cells are a treatment option for patients with cancers susceptible to NK cell lysis, including blood cancers (such as acute myeloid leukemia or multiple myeloma) and several solid tumors (e.g. brain tumor, Ewing sarcoma and rhabdomyosarcoma). Increased numbers of functional NK cells can also significantly enhance the efficacy of therapeutic antibodies used in treatment of several cancers, including lymphomas, colorectal cancer, lung cancer, and breast cancer, among others.
Nevertheless, Copik et al. note this type of therapy is expensive, thus there was a motivation in the art to expand NK cells to a degree that they reach “an effective therapeutic dose” (see paragraphs [0034]-[0035]). The ‘448 document in turn teaches that VDUP1 administration increases NK cell differentiation and cytotoxicity (see above), which would also increase the therapeutic dose of NK cells. Furthermore, the person of ordinary skill in the art could have reasonably expected success because NK cell infusion was known in the art as an acceptable cancer treatment.
Thus, the claims do not contribute anything non-obvious over the prior art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Ramakrishna et al. (WO2007150077—on IDS filed 09/03/2025) teaches “[a] method for treating a subject with cancer…comprising administering to said subject induced cytotoxic T lymphocytes (CTLs) in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines, said CTLs induced by a process comprising inducing a CTL in vitro that is specific for said tumor cells by contacting a precursor CTL with: at least one polypeptide comprising an epitopic peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 355 to 693 under conditions that generate a CTL response to said tumor cells” (see claim 20). According to the sequence listing by Ramakrishna et al., SEQ ID NO: 664, VDUP1 or thioredoxin interacting protein, comprises the instant peptide set forth in SEQ ID NO: 1:
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 61 100.0 391 1 AASEQ2_08142026_113154
ALIGNMENTS
RESULT 1
AASEQ2_08142026_113154
Query Match 100.0%; Score 61; DB 1; Length 391;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSKKVILDLPLVI 13
|||||||||||||
Db 284 GSKKVILDLPLVI 296
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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