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 .
Response to Amendment
This office action is responsive to the amendment filed on 12/17/25. As directed by the amendment: no claims have been amended, claims 11-20, 26-38, and 44-46 have been cancelled, and no new claims have been added. Thus, claims 1-10, 21-25, and 39-43 are presently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-10 and 21-25) in the reply filed on 12/17/25 is acknowledged. Claims 39-43 are withdrawn from consideration.
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 9 and 23 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.
Regarding claims 9 and 23, “the laser energy” (claim 9) and “the fractional laser” (claim 23) lack antecedent basis in the claims. For the purposes of examination, the limitation in claim 23 will be interpreted to refer to not being treated with energy of claim 1.
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.
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.
Claim(s) 1, 3-8, 10, and 21-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Optimizing Timing of lmmunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy" by Young et al. (hereinafter 'Young').
Regarding claims 1, 4, and 5, Young discloses a method for inducing an immune response in a subject in need thereof, the method comprising: (a) administering an inhibitor of a blocking checkpoint molecule and an agonist of a stimulative checkpoint molecule to a subject in need thereof, and (b) treating a tissue of the subject with energy to induce tissue damage (abstract - 'Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody ... Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures."), wherein an immune response is increased compared to the immune response produced by the inhibitor of the blocking checkpoint molecule and the agonist of the stimulative checkpoint molecule in the absence of the tissue damage (abstract; pg. 9, par. 2 -"lmmunotherapy with anti-OX40 has been shown to synergize well with anti-CTLA4 (24]. therefore we tested the effect of combining antiCTLA4 at its optimum timing pre-radiation with anti-OX40 post-radiation .... Combination treatment with anti-CTLA4, anti-OX40 and radiation resulted in significantly extended survival compared to anti-CTLA4+anti-OX40 (p<0.001 ), RT alone (p<0.01 ), RT +anti-OX40 (p<0.05) and RT +anti-CTLA4 (p<0.05)"; pg. 11, par. 2 - "In order to avoid confounding factors of variations within the radiation dose or fractionation a single high dose treatment was chosen."), except for specifically disclosing the energy inducing fractional tissue damage. However, Young further teaches fractional radiation may be used to treat tumors (pg. 11, par. 2-3 - "In order to avoid confounding factors of variations within the radiation dose or fractionation a single high dose treatment was chosen. Clinically, radiation dose and fractionation vary from a single high-dose treatment such as in early stage lung cancer and limited oligometastatic disease to low dose treatments delivered daily over weeks for both definitive and adjuvant treatment. As lower doses and or fractionated dose patterns may affect immune cell priming, trafficking and survival, loss of immunologic responses with radiation may be seen and may confound questions of timing."). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, as disclosed by Young, to include or instead use fractional tissue damage delivered by a fractional dose pattern, as disclosed by Young, since fractional radiotherapy is known in the art and the choice of hypofractional therapy was made solely to ensure confounding factors during the experiments of Young, and since this would afford any improved or altered activity of the anti-CTLA4/anti-OX40 combination therapy.
Regarding claim 3, Young further discloses the energy is ionizing radiation (pg. 3, par. 2).
Regarding claim 6, Young additionally discloses the blocking checkpoint module is PD-1 (pg. 12).
Regarding claim 7, Young additionally discloses the OX40 agonist comprises an antibody (abstract).
Regarding claim 8, Young discloses the cancer is at least melanoma and/or breast cancer (see Discussion section).
Regarding claim 10, Young discloses the immune response is local and/or systemic (any immune response will inherently be at least one of these options; see also Discussion section, and pg. 4, par. 1).
Regarding claims 21-25, claim 23 as best understood, Young discloses the immune response comprises an anti-tumor response (see at least the first paragraph of the Introduction on pg. 1-2) comprising a systemic response (see also Discussion section and pg. 4, par. 1), inducing abscopal effect against a tumor not treated with factional tissue damage (see at least the first paragraph of the Introduction on pg. 1-2), reducing the likelihood of recurrence (see at least the first paragraph of the Introduction on pg. 1-2), increases progression-free survival, reduces the size of one or more tumors, and/or increases overall response rate (see at least the first paragraph of the Introduction on pg. 1-2).
Claim(s) 2 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Young in view of “Fractional Laser Releases Tumor-Associated Antigens in Poorly Immunogenic Tumor and Induces Systemic Immunity” by Kawakubo et al. (hereinafter “Kawakubo”).
Regarding claims 2 and 9, claim 9 as best understood, Young teaches the method as claimed, except for the fractional tissue damage induces CDS+ T cell recruitment and/or activation and/or the laser energy is emitted from a fractional CO2 laser. However, Kawakubo discloses administration of an inhibitor of a blocking checkpoint molecule in combination with fractional tissue damage delivered by a CO2 laser, and where fractional tissue damage induces CDS+ T cell recruitment and/or activation (abstract). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, as disclosed by Young, to include or instead use a method of fractional tissue damage which induces CDS+ T cell activation, as disclosed by Kawakubo, since this would afford improved immune cell activation and therefore any improved clinical outcome when used in a combination therapy with immunotherapy.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: see attached notice of references cited.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN R PRICE whose telephone number is (571)270-5421. The examiner can normally be reached Mon-Fri 8:00am-4:00pm Eastern time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Tsai can be reached at 571-270-5246. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NATHAN R PRICE/Primary Examiner, Art Unit 3783