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
Claims 1-20 are pending. Claims 7-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Therefore, Claims 1-6 and 12-20 are examined.
Election/Restrictions
Applicant’s election without traverse of colon cancer, ATRA as the specific retinoid used, and retinoid/radiation therapy alone in the reply filed on 2/26/2026 is acknowledged.
Claims 7-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/26/2026.
Priority
This application claims priority to and benefit of U.S. Provisional Patent Application Serial No. 63/348,745, filed June 3, 2022.
Information Disclosure Statement
No Information Disclosure Statement was filed in the application.
Claim Objections
Claim 6 is objected to because of the following informalities: the text at the end of the claim bridging the last two lines beginning with the term “optionally…” should be deleted because it is redundant since colon cancer and kidney cancer are already mentioned earlier in the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-6, 12, and 14-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rao et al. (Sci Immunol. 2021 June 15; 6(60): doi:10.1126/sciimmunol.aba8426.)
Claimed invention
Claim 1 is drawn to a method for treating a cancer (particularly colon cancer) in a subject in need thereof, the method comprising:
administering to the subject a retinoid (particularly all-trans retinoic acid, “ATRA”); and
exposing at least a portion of the subject to ionizing irradiation energy.
Prior art
Rao teaches a method for treating colon cancer by administering a retinoid and exposing the subject to ionizing radiation. Specifically, Rao teaches: “To examine the effect of the combination of local IR [ionizing radiation] with RA [all-trans retinoic acid, “ATRA”] on tumor growth, we treated established syngeneic mouse MC38 colon carcinoma tumors by oral gavage with oil (control), RA (400 μg/dose), local IR (15 Gy), or IR plus RA (IR + RA).” (Rao, p. 3., ‘Results’ section; see Abstract also.) “IR alone inhibited tumor growth, while RA had no significant effect on MC38 tumor growth. The combination of IR with RA synergistically inhibited tumor growth compared to either the untreated controls or any single treatment.” (Id.; see also Fig. 1B).
Therefore, Rao anticipates Claim 1.
Claim 2 limits claim 1, wherein the retinoid is selected from the group consisting of a retinoic acid (such as ATRA – Claim 3, Claim 4) and is administered orally (Claim 12). Claim 5 limits claim 1, wherein the cancer is a solid tumor cancer (such as colon cancer Claim 6). As indicated above, treatment included orally administering ATRA in combination with ionizing irradiation.
Claims 14-20 – “wherein the method obtains intended results or outcomes”
Claims 14-20 recite the intended outcomes of performing the combination of administering and exposing steps recited in Claim 1, wherein the combination provides:
CLAIM
enhanced tumor growth control compared to a treatment comprising the administering alone or the exposing alone;
enhanced tumor growth control for a tumor not directly targeted by said administering and/or said exposing;
enhanced or comparable tumor growth control using a lower total dose of ionizing radiation energy compared to a treatment consisting of exposing the subject to ionizing radiation alone;
an increase in inducible nitric oxide synthase (iNOS)-producing myeloid cells in the subject; an increased level of CD11b+iNOS+ cells in a tumor in the subject;
an increase in tumor necrosis factor-alpha (TNF-a)-producing myeloid;
cells in the subject; and
protection from tumor recurrence.
The method has intended results that do not give further meaning and purpose to the manipulative steps of the claimed method. Therefore, the limitations are not given patentable weight because they simply express the intended result of the process steps positively recited. Accordingly, a reference need not expressly teach the intended outcomes to meet the claim limitations. Thus, the claims are anticipated as they fall along with 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.
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.
A. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Rao et al. (Sci Immunol. 2021 June 15; 6(60): doi:10.1126/sciimmunol.aba8426) in view of Gong et al. (Journal for ImmunoTherapy of Cancer (2018) 6:46.)
Claimed invention
Claim 13 limits claim 1, wherein the exposing is performed by exposing said at least a portion of the subject to a fraction of a total dose of ionizing irradiation energy on two or more separate days until said at least a portion of the subject is exposed to said total dose of ionizing irradiation energy, optionally wherein said two or more separate days are two or more consecutive days.
Prior art
Rao anticipates Claim 1 as outlined above but it differs from Claim 13 because it does not fractionate the total irradiation over days.
However, Gong, teaches radiation dose and fractionation in the context of radiation antitumor immunity. (Gong, p. 11.) Gong teaches that at single fraction doses of 15 Gym dose-dependent increases in regulatory T cells (Tregs) were observed with no corresponding improvement in antitumor immune responses and states: “Fractionation of the 15 Gy generally resulted in superior immune responses compared to single-fraction 15 Gy.” Thus, Gong teaches administering the total dose of 15y in fractions over multiple days rather than as a single fraction produces superior immune-mediated antitumor responses.
A person of ordinary skill in the art (POSA) would have found it obvious to treat colon cancer with ATRA and IR of 15 Gy total radiation dose ( as described by Rao) in fractions over at least 2 days because Gong teaches that fractionating the total dose of 15 Gy produces superior immune responses compared to administration as a single fraction. The POSA would have had a reasonable expectation that fractionated delivery of 15 Gy dose over at least two days would preserve or enhance the antitumor effect of the IR+ATRA combination disclosed by Rao.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the application was filed.
B. Claims 1-6 and 12-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over
Anand et al. (US 2019/0330632) in view of Li et al. (“All-Trans Retinoic Acid Enhances Chemosensitivity to 5-FU by Targeting miR-378c/E2F7 Axis in Colorectal Cancer.” J Oncol. 2021 Jul 19;2021:5338934. doi: 10.1155/2021/5338934.)
Claimed invention
Claim 1 is drawn to a method for treating a cancer (particularly colon cancer) in a subject in need thereof, the method comprising:
administering to the subject a retinoid (particularly all-trans retinoic acid, “ATRA”); and
exposing at least a portion of the subject to ionizing irradiation energy.
Prior art
Anand teaches a method of treating colorectal cancer in a subject comprising administering a pharmaceutical composition comprising an effective amount of miR-451a to colorectal cancer cells within the subject and administering a dose of at least 1 Gy of ionizing radiation to the colorectal cancer cell. (Anand, Claims 1,2,17.) The method further includes administering doses of one or more chemotherapeutic agents (e.g., 5-fluorouracil (5-FU), bevacizumab, cetuximab, panitumumab, regorafeni, irinotecan, etc.) to the subject. (Anand, Claims 11,13 ; see also 0039-0041.)
While Anand teaches treating colorectal cancer in a patient comprising exposing a portion of the patient to radiation and further administering one or more chemotherapeutic agents, Anand does not teach the administration of a retinoic acid such as ATRA as the chemotherapeutic agent.
However, ATRA was already suggested for treatment of colon cancer. For example, Li teaches clinical trials revealed that ATRA could inhibit proliferation and promote cell apoptosis in CRC. Li also teaches combination therapy of CRC with ATRA and 5-FU. (Li, abstract, ‘Discussion’, ‘Conclusion’.)
A person of ordinary skill in the art (POSA) would have found it obvious to treat CRC with ionizing radiation and ATRA because Anand teaches a method for treating CRC with a combination of ionizing radiation and one or more chemotherapeutic agents including 5-FU and Li teaches ATRA is effective against the same cancer and may be combined with 5-FU. The POSA would have had a reasonable expectation of success in the addition of ATRA with the ionizing radiation and 5-FU of Anand for treating CRC because each of these therapies are disclosed as being useful for treating this cancer. Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 2 limits claim 1, wherein the retinoid is selected from the group consisting of a retinoic acid (such as ATRA – Claim 3, Claim 4) and is administered orally (Claim 12). Claim 5 limits claim 1, wherein the cancer is a solid tumor cancer (such as colon cancer Claim 6). As indicated above, the prior art suggests CRC treatment by administering ATRA in combination with ionizing irradiation. Given that Anand discloses that the additional chemotherapeutic agent may be administered by different routes including orally (Anand, 0051,0098), the POSA would have found it obvious to administer ATRA by routes described for further chemotherapeutic administration including the oral route.
Claim 13 limits claim 1, wherein the exposing is performed by exposing said at least a portion of the subject to a fraction of a total dose of ionizing irradiation energy on two or more separate days until said at least a portion of the subject is exposed to said total dose of ionizing irradiation energy, optionally wherein said two or more separate days are two or more consecutive days. Anand teaches the total ionizing radiation may be administered in fractionated doses over two or more days:
“the ionizing radiation can be administered at 2 Gy per dose for a total cumulative dose of from about 30 Gy to about 60 Gy…at 2 Gy per dose for a total cumulative dose of from about 40 Gy to about 60 Gy…at 5 Gy per dose for a total cumulative dose of from about 15 Gy to about 30 Gy…at 5 Gy per dose for a total cumulative dose of from about 20 Gy to about 30 Gy…at 5 Gy per dose for a total cumulative dose of about 25 Gy.” (Anand, 0038.)
The “per dose” language in combination with the total cumulative dose indicates that the radiation exposure occurs over multiple separate exposure. A POSA would reasonably understand that each fractionated dose can occur over multiple days of exposure instead of a full total dose of 60 Gy on a single day.
Claims 14-20 – “wherein the method obtains intended results or outcomes”
Claims 14-20 recite the intended outcomes of performing the combination of administering and exposing steps recited in Claim 1, wherein the combination provides:
CLAIM
enhanced tumor growth control compared to a treatment comprising the administering alone or the exposing alone;
enhanced tumor growth control for a tumor not directly targeted by said administering and/or said exposing;
enhanced or comparable tumor growth control using a lower total dose of ionizing radiation energy compared to a treatment consisting of exposing the subject to ionizing radiation alone;
an increase in inducible nitric oxide synthase (iNOS)-producing myeloid cells in the subject; an increased level of CD11b+iNOS+ cells in a tumor in the subject;
an increase in tumor necrosis factor-alpha (TNF-a)-producing myeloid;
cells in the subject; and
protection from tumor recurrence.
The method has intended results that do not give further meaning and purpose to the manipulative steps of the claimed method. Therefore, the limitations are not given patentable weight because they simply express the intended result of the process steps positively recited. Accordingly, a reference need not expressly teach the intended outcomes to meet the claim limitations.
Pertinent prior art not applied in the current rejections
Edwards et al. (OnLine Journal of Biological Sciences 14 (2): 102-107, 2014.) – teaching ATRA used for colon cancer. (Abstract, see also p. 106.)
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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