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 .
Applicant’s response on July 28, 2025 is acknowledged. Claims 1, 5, 8, 11-14, 16, 19-22, and 27 were amended. Claims 1, 5, 8, 11-14, 16, 19-22, 25-27 and 32 are pending and under examination in this Office action.
New Rejection necessitated by Applicant’s amendment
Claim Rejections - 35 USC § 112
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 1, 5, 8, 11-14, 16, 19-22, 25-27 and 32 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Applicant amended claim 1 to recite “wherein the modified CAR T cell does not comprise exogenous IL-12α p35 subunit or IL-23 p19 subunit, wherein the T cell, upon activation, produces IL-23.
Applicant argues that the support for this amendment can be found in paragraph [0042] of the present specification.
In response, Examiner notes that paragraph [0042] does not recite support for this amendment. Examiner cannot find support for this amendment throughout the Specification.
Paragraph [0042] Disclosed herein are methods of increasing T cell proliferation. In some embodiments, the method includes modifying a T cell to comprise an IL12β p40 subunit.
Thus, the claims are rejected for reciting new matter.
Claim Rejections - 35 USC § 102
Rejection of Claim 1-2, 4-7, 14, 16, 19-21, 23, 25-27 and 32 under 35 U.S.C. 102(a)(1) as being anticipated by Chmielewski et al. (American Association of Cancer Research, January 2011, p. 5697-5706 in IDS on 12/12/22) is withdrawn in view of Applicant’s amendment.
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.
Rejection of Claims 1, 5, 8, 11-14, 16, 19-22, 25-27 and 32 are rejected under 35 U.S.C. 35 U.S.C. 103 as being unpatentable over Chmielewski et al. (American Association of Cancer Research, January 2011, p. 5697-5706 in IDS on 12/12/22) in view of Yun et al., (US Patent 8,298,790) and Parham et al., (Journal of Immunology, p. 5699-5708 in IDS on 12/12/22) and Liu et al. (Current Immunology Review, 2005, p. 1-33) is maintained and modified to address the new limitation.
Regarding the claim limitation “wherein the modified CAR T cell does not comprise exogenous IL-12α p35 subunit or IL-23 p19 subunit, wherein the T cell, upon activation, produces IL-23”, it is the Examiner’s position that Chmielewski does not disclose the presence of the exogenous IL-12α p35 subunit or IL-23 p19 subunit. It is thus the Examiner’s position that the composition in Chmielewski does not comprise the exogenous IL-12α p35 subunit or IL-23 p19 subunit. The prior art by Liu et al. teaches against adding the exogenous IL-12p35 subunit.
The skilled artisan would not want to add the exogenous IL-12p35 subunit to modified CAR T cell of Chmielewski because Liu teaches that the exogenous IL-12p35 subunit it has immunosuppressive effects like suppressing T and B cell proliferation and inducing regulatory cells, while the exogenous IL-23p19 subunit is the key component of IL-23, a pro-inflammatory cytokine that helps maintain and expand inflammatory Th17 responses.
Thus, the present claims as amended, would have been prima facie obvious at the time of the present invention.
Chmielewski discloses a modified T cell; abstract) comprising a iL12beta p40 subunit (page 5698, second column, second paragraph; page 5699, second column, second paragraph).
As per claim 2, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell expresses p40 (page 5699, second column, second paragraph).
As per claim 4, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell is a CAR (abstract) or TCR-engineered T cell.
As per claim 5, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell exhibits mi increased cell division (wherein the T cell exhibits reduced apoptosis (wherein the T cell exhibits increased cell division), page 5702, second column).
As per claim 6, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell exhibits reduced apoptosis (wherein the T cell exhibits reduced apoptosis; page 5702, second column).
As per claim 7, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell exhibits increased T cell proliferation (has the advantage to avoid apoptosis of engineered T cells during ex vivo amplification (wherein the T cell exhibits increased T cell proliferation); page 5702, second column).
As per claim 13, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell maintains production of IFNy and TNFa, as compared to a control cell (wherein the T cell maintains production of IFNy and TNFa, as compared to a control cell; page 5698, first column, first paragraph; page 5699, second column, second paragraph; figure 1A; figure 5 legend).
As per claim 14, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell promotes enhanced tumor control and improved survival, as compared to a control cell (wherein the T cell promotes enhanced tumor control and improved survival, as compared to a control cell; page 5966, second column, first - second paragraphs).
As per claim 15, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell exhibits increased antitumor activity (wherein the T cell exhibits increased antitumor activity; page 5966, second column, first, second paragraphs).
As per claim 17, Chmielewski discloses the modified T cell of claim 1, and Chmielewski further discloses wherein the T cell is a non-human T cell (mouse (non-human) T cell; page 5698, second column, fourth paragraph).
As per claim 18, Chmielewski discloses the modified T cell of claim 17, and Chmielewski further discloses wherein the T cell is a mouse T cell (mouse T cell; page 5698, second column, fourth paragraph).
As per claim 20, Chmielewski discloses a method of increasing T cell proliferation (engineered T cells continuously produce IL-12 having the advantage to avoid apoptosis of engineered T cells during ex vivo amplification (a method of increasing T cell proliferation); page 5702, second column) comprising modifying a T cell to comprise a IL12beta p40 subunit (comprising modifying a T cell to comprise a IL12beta p40 subunit; abstract; page 5698, second column, second paragraph; page 5699, second column, second paragraph).
As per claim 21, Chmielewski discloses a method of treating cancer (destruction of antigen-loss cancer cells that would normally escape (a method of treating cancer); abstract) comprising administering to a subject a modified T cell comprising an IL12beta p40 subunit.
Chmielewski teach the claimed invention as discussed above. Chmielewski does not teach that the T cell upon activation produces IL23.
Yun discloses a modified cell (transformed host cells (modified cell); abstract) comprising a IL12beta p40 subunit (comprising a IL12beta p40 subunit; abstract). Yun does not disclose a modified T cell.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of Yun, to include a modified T cell, as disclosed by Chmielewski, in order to provide a superior less toxic method for targeting inaccessible tumor lesions.
As per claim 3, Yun and Chmielewski, in combination, disclose the modified T cell of claim 1, and Yun further discloses wherein the cell, upon activation, produces IL23 (wherein the cell, upon activation, produces IL23; abstract; column 5, lines 16-20, 40-51; claim 1). Yun does not disclose a T cell. Chmielewski discloses a T cell (T cell; abstract).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of Yun, to include a modified T cell, as disclosed by Chmielewski, in order to provide a superior less toxic method for targeting inaccessible tumor lesions.
As per claim 21, Yun discloses a method of treating cancer (a pharmaceutical anti-tumor composition (a method of treating cancer); abstract; column 11, lines 10-14) comprising administering to a subject a modified cell (column 12, lines 3-12) comprising a IL12beta p40 subunit (comprising a IL12beta p40 subunit; abstract). Yun does not disclose a modified T cell. Chmielewski discloses a modified T cell (engineered (modified) T cell; abstract).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of Yun, to include a modified T cell, as disclosed by Chmielewski, in order to provide a superior less toxic method for targeting inaccessible tumor lesions.
Chmielewski does not disclose wherein the T cell, upon activation, exhibits increased STAT3 phosphorylation; wherein the T cell, upon activation, exhibits differentiation expression of one or more STAT3 regulated genes selected from the group consisting of: SOX2, SOCS3, CEBPD, IFIT1, IFIT3, USP18, COKN2B, and combinations thereof: or wherein the T cell, upon activation, activates the STAT3 pathway.
Parham, et al. teaches that the IL-23R associates in a ligand-dependent manner STAT3 (abstract). It would have been within the skill of the ordinary artisan to expect increased STAT3 phosphorylation upon T cell activation.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Contact Information
Applicant’s amendment necessitated new grounds o rejection present in this Office action. Thus, 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 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.
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 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 AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/ Primary Examiner, Art Unit 1672