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 .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-6) in the reply filed on November 3, 2025 is acknowledged. The traversal is on the grounds that a serious search burden is not required. In addition, Applicant asserts that any search for the method of inhibiting Sirt2 would necessarily be a search for a therapeutic cell and a method of providing an anti-cancer immunity to a subject. This is not found persuasive because the cell prepared by inhibiting or ablating SIRT2 does not necessarily provide a therapeutic effect, nor is the therapeutic effect specified. In addition, while SIRT2 does appear to have an anticancer effect, it has not been shown that inhibiting or ablating SIRT2 will provide an anti-cancer immunity to all subjects having or at risk of developing all types of cancer. For example, Wang et al. (55 Ageing Research Reviews 100961, 1-15 (2019)) is a post-filing article that discloses, that while SIRT2 is a potential therapeutic target for a variety of diseases (abstract), shows inconsistencies in data relating to SIRT2 breast cancer research (page 8, column 2) and that SIRT2 is downregulated in non-small cell lung cancer compared to non-tumor tissues, with low levels associated with poor patient survival (page 8, column 2). Thus, the searches for Group II and Group III are not deemed to be co-extensive and would provide a serious search burden to examine all groups together.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-6 are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed May 27, 2021; February 7, 2024; and November 3, 2025 (2) have been considered.
Drawings
The drawings are objected to because Figures 24A and 24B contain sequences without accompanying sequence identifiers. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The Sequence Listing Incorporation by Reference paragraph does not list the size of the ASCII
text file, which appears to be 4,087 bytes.
Specification
The disclosure is objected to because of the following informalities:
At page 5, line 1, “BRIEF” should be inserted before “DESCRIPTION OF DRAWINGS.”
At page 26, “AIM1” should be changed to “AEM1.”
At page 27, “AIM2” should be changed to “AEM2.”
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at paragraph [0335]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms ELISPOT at paragraphs [0019], [0021], [0023], [0029]-[0030], [0033], [0039], [0047], [0054], [0229], and [0290]-[0291], SEAHORSE at paragraphs [0021], [0023], [0028]-[0030], [0036], [0039], [0047], [0054], [0195], [0239], [0256], [0295], and [0357], OXPHOS at paragraphs [0047], [0360], and [0362], CAMPATH at paragraph [0136], RITUXAN at paragraph [0142], HERCEPTIN at paragraph [0142], VIDAZA at paragraph [0147], GLIVEC at paragraph [0151], GLEEVEC at paragraph [0151], ZENAPAX at paragraph [0152], SIMULECT at paragraph [0152], REMICADE at paragraph [0152], HUMIRA at paragraph [0152], TYSABRI at paragraph [0152], XOLAIR at paragraph [0152], RAPTIVA at paragraph [0152], BIOXCELL at paragraphs [0181], [0266], and [0273], ALEXAFLUOR at paragraphs [0185]-[0186] and [0287], CELL-TAK at paragraph [0196], YSI at paragraphs [0201] and [0307], NONIDET at paragraphs [0205] and [0311], PHOSSTOP at paragraph [0207], SUPERSIGNAL at paragraphs [0207] and [0314], AMERSHAM at paragraph [0208], ZIPTIP at paragraph [0212], SEP-PAK at paragraphs [0213] and [0320], DIONEX at paragraphs [0215] and [0322], ORBITRAP at paragraph [0215], MASCOT at paragraphs [0216] and [0323], SEQUEST at paragraphs [0216] and [0323], IMMUNOBLOT at paragraphs [0237] and [0348], RNEASY at paragraph [0317], NUGEN at paragraphs [0317], NEXTSEQ at paragraph [0317], TAPESTATION at paragraph [0317], ACQUITY at paragraph [0320], ACCUCORE at paragraph [0331], and GRAPHPAD at paragraph [0337], 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 terms should be capitalized wherever they appear 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.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
At claim 1, line 3, “Sirt2” should be changed to “sirtuin2.”
Appropriate correction is required.
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.
Claims 4-5 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 4 recites that the genetic modification of the lymphocytes is insertion of a chimeric receptor into the genome of the cell at a location that disrupts expression or activity of an endogenous Sirt2 protein. However, the chimeric receptor appears to be a polypeptide, which can be a chimeric antigen receptor (CAR) polypeptide (claim 5). It is not clear how insertion of a polypeptide can be made into the genome of a cell. If Applicant intends to insert a nucleic acid molecule encoding the polypeptide, the claim can be amended.
Claim 4 recites the limitation "the cell" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the cell” be changed to “the lymphocytes.”
Claim 5 depends from claim 4, and is therefore included in these rejections.
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.
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 1-2 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Dudley et al. (U.S. Patent Application Publication No. 2011/0268754, published November 3, 2011, and cited in the Information Disclosure Statement filed May 28, 2021) in view of Spiegelman et al. (13 ChemMedChem 1890-1894 (2018)) or Hoffman et al. (289(8) The Journal of Biological Chemistry 5208-5216 (2014)) or Cheon et al. (356 Cancer Letters 637-645 (2015)).
Regarding claim 1, Dudley discloses a method that comprises collecting lymphocytes from a subject having cancer (paragraph [0011]). Dudley discloses that isolated cells can be selected for highly avid recognition of a cancer antigen and expanded (paragraph [0014]). Dudley discloses that these cells can be isolated from a mammal by any suitable means (paragraph [0024]). Dudley discloses that, during expansion, the lymphocytes can be treated with a T-cell growth factor or genetically modified (paragraph [0015]). Dudley discloses that biopsied specimens contain necrotic tumor tissue and areas of dens, diffuse lymphocytic infiltrates, which consist predominately of CD8+ cells (paragraphs [0022] and [0031]).
Regarding claim 6, Dudley discloses treatment of cancer patients with tumor-infiltrating lymphocytes (TILs), which were screened for tumor cell recognition (paragraphs [0030]-[0037]).
Dudley does not disclose or suggest treating the lymphocytes with a Sirt2 inhibitor or genetically modifying the lymphocytes to inhibit or ablate SIRT2 expression.
Regarding claim 2, Spiegelman discloses that sirtuin inhibitors have been researched and developed, with some exhibiting anti-cancer activity (abstract). Spiegelman discloses several SIRT2 inhibitors including AGK2, SirReal2, Tenovin-6, and thiomyristoyl (TM) (abstract and Figure 1). Spiegleman discloses that Tenovin-6 was the most potent, but TM showed cancer-cell-specific toxicity (abstract).
Regarding claim 2, Hoffman discloses SIRT2 inhibitors that provide pro-apoptotic activity in non-small cell lung cancer (abstract). Hoffman discloses that the inhibitors AEM1 and AEM2 are selective inhibitors of SIRT2 (abstract).
Regarding claim 2, Cheon disclose a specific SIRT2 inhibitor that induces cell cycle arrest by downregulation of Snail transcription factor (abstract). Cheon discloses that the inhibitor AK-1 is an SIRT2 inhibitor (abstract).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to collect lymphocytes according to Dudley and to treat them with the SiRT2 inhibitors of Spiegelman or Hoffman or Cheon because, as disclosed by Spiegelman, Hoffman, and Cheon, such inhibitors can be used to provide toxicity to the cancer cells/lymphocytes of Dudley. One of ordinary skill in the art would have been motivated to use the SiRT2 inhibitors in order inhibit or ablate SIRT2 expression in the isolated lymphocytes of the subject from whom they were obtained.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Dudley in view of Spiegelman, Hoffman, or Cheon as applied to claims 1-2 and 6 above, and further in view of Kim et al. (U.S. Patent Application No. 2017/0128459, published May 11, 2017, and cited in the Information Disclosure Statement filed November 3, 2025).
Dudley, Spiegelman, Hoffman, and Cheon disclose a method of inhibiting or ablating SIRT2 expression in lymphocytes, as discussed above.
Dudley, Spiegelman, Hoffman, and Cheon fail to disclose or suggest that the inhibitor is an siRNA, an antisense oligonucleotide, or a gRNA oligonucleotide.
Kim discloses compositions comprising an SIRT2 inhibitor for treating renal inflammatory diseases caused by sepsis (abstract). Kim discloses that the SIRT2 inhibitor can be an antisense oligonucleotide, an siRNA, or an SIRT2-specific antibody (paragraphs [0022] and [0029]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Kim’s antisense oligonucleotide, siRNA or SIRT2-specific antibody in place Spiegelman’s, Hoffman’s, or Cheon’s SIRT2 inhibitors in the method disclosed and suggested by Dudley and Spiegelman because both Kim’s SIRT2 inhibitors and Spiegelman’s SIRT2 inhibitors, while of different structure and method of action, all provide the same effect, which is to inhibit or ablate SIRT2 expression. Thus, one of ordinary skill in the art would be able to choose from a wide variety of potential SIRT2 inhibitors, each of which provides the required inhibition/ablation of SIRT2 expression.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Dudley in view of Spiegelman, Hoffman, or Cheon, as applied to claims 1-2 and 6 above, and further in view of Porter et al. (365(8) The New England Journal of Medicine 725-733 (2011), and cited in the Information Disclosure Statement filed November 3, 2025).
Dudley, Spiegelman, Hoffman, and Cheon disclose a method of inhibiting or ablating SIRT2 expression in lymphocytes, as discussed above.
Dudley, Spiegelman, Hoffman, and Cheon fail to disclose or suggest that the SIRT2 is disrupted by inserting a sequence of a chimeric receptor into the genome, where the chimeric receptor can be a chimeric antigen receptor (CAR).
Regarding claims 4-5, Porter discloses a vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, with CD137 (a receptor in T-cells) and CD3-zeta (a gingal-transduction component of the T-cell antigen receptor) (abstract). Porter discloses that T-cells can be genetically modified to stably express antibodies on their surface, conferring new antigen specificity (page 725, first paragraph). Porter discloses obtaining T-cells from patients and transducing them with the vector encoding the chimeric antigen receptor (page 726, column 2, third paragraph).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to design chimeric antigen receptor (CAR) according to Porter in order to insert the sequence encoding the CAR within the gene encoding SIRT2 in T-cells according to Dudley, Spiegelman, Hoffman, and Cheon, which will have the effect of disrupting the SIRT2 gene, thus ablating expression of the gene and providing a CAR T-cell that can be used to provide a therapeutic effect. One of ordinary skill in the art would have been motivated to insert a sequence encoding a CAR into the SIRT2 locus because this is another method of inhibiting/ablating expression of SIRT2 in a lymphocyte obtained from a subject having cancer, and thus Porter’s CAR can be used in place of SIRT2 inhibitors of Dudley, Spiegelman, Hoffman, and Cheon to obtain the same effect.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636