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 .
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 14-15 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.
Claims 14 and 15 are now depending on a claim (which 13) that is now being cancelled by Applicant. It is unclear what the parent claim is. The Examiner assume it is claim 1, but claim 1 does not have a radiotherapy. So “the radiotherapy” in these claims also lack antecedent basis.
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.
Claim(s) 1-4, 6, 8-11, 14-15, 18-21, 29-33, 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wedekind et al. (US 2009/0099105, hereinafter Wedekind ‘105) in view of Mulvey et al. (US 2017/0173092, hereinafter Mulvey ‘092).
In re claim 1, Wedekind ‘105 teaches a method of radio-sensitizing a cell in vivo, comprising: contacting (0055, 0216, 0217, 0237-0248) the cell in a subject with an exogenous cytidine deaminase inhibitor compound (0041, 0223, 0275), wherein the subject is a human or animal (0219, 0222), but fails to teach further comprising contacting the cell with radiation.
It would have been prima facie obvious to one of ordinary skills in the art at the time of invention to modify the method/device of Wedekind ‘105 to include the features of Mulvey ‘092 in order to enhance the sensitivity of the tumor cells to the particular therapeutic agent.
In re claim 2, Wedekind ‘105 teaches wherein the exogenous cytidine deaminase inhibitor compound is capable of inhibiting an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) enzyme (0012, 0023, 0024, 0027, 0028, 0034-0038, 0230, etc.).
In re claim 3, Wedekind ‘105 teaches wherein the APOBEC enzyme is one or more of: an APOBEC1 enzyme, an APOBEC3A enzyme, an APOBEC3B enzyme, an APOBEC3C enzyme, an APOBEC3D enzyme, an APOBEC3E enzyme, an APOBEC3F enzyme, an APOBEC3G enzyme, an APOBEC3H enzyme, and an activation-induced cytidine deaminase (AID) enzyme (0034-0038, table 1).
In re claim 4, Wedekind ‘105 teaches wherein the cell is a cancer cell (0059, 0219, 0222).
In re claim 6, Wedekind ‘105 teaches further comprising contacting the cell with two or more exogenous cytidine deaminase inhibitor compounds (0035).
In re claim 8, Wedekind ‘105 teaches wherein the contacting comprises administering the exogenous cytidine deaminase inhibitor compound to the subject (0056, 0216, 0217-0221).
In re claim 9, Wedekind ‘105 teaches wherein the subject has a cancer (0059, 0219, 0222).
In re claim 10, Wedekind ‘105 teaches wherein the cancer is a cancer with elevated APOBEC activity (0051, 0222, 0230, 0250).
In re claim 11, Wedekind ‘105 teaches wherein the cancer is a bone cancer, a soft tissue cancer, a colon cancer, a rectal cancer, an esophageal cancer, a lung cancer, a central nervous system (CNS) cancer, breast cancer or uterine cancer (0222).
In re claim 14, Mulvey ‘092 teaches to teach wherein the radiotherapy comprises external beam radiation (0124-0126, note that at least the proton therapy is external beam radiation).
In re claim 15, Mulvey ‘092 teaches to teach wherein the radiotherapy comprises brachytherapy (0124).
In re claim 18, Wedekind ‘105 teaches wherein the exogenous cytidine deaminase inhibitor compound is in a pharmaceutical composition and wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier (0215-0216).
In re claim 19, Wedekind ‘105 teaches a method of enhancing efficacy of a effects of “enhances the efficacy of the administered radiotherapy in the subject.” Applicant has not limited any method that would make this administration or make the inhibitor different from the prior art).
Wedekind ‘105 fails to teach (i) the subject is administered a radiotherapy.
Mulvey ‘092 teaches concurrently use of radiation therapy and chemotherapy with exogenous inhibitor (0125).
It would have been prima facie obvious to one of ordinary skills in the art at the time of invention to modify the method/device of Wedekind ‘105 to include the features of Mulvey ‘092 in order to enhance the sensitivity of the tumor cells to the particular therapeutic agent.
In re claim 20, Wedekind ‘105 teaches wherein the exogenous cytidine deaminase inhibitor compound is capable of inhibiting an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) enzyme (0012, 0023, 0024, 0027, 0028, 0034-0038, 0230, etc.).
In re claim 21, Wedekind ‘105 teaches wherein the APOBEC enzyme is one or more of: an APOBEC1 enzyme, an APOBEC3A enzyme, an APOBEC3B enzyme, an APOBEC3C enzyme, an APOBEC3D enzyme, an APOBEC3E enzyme, an APOBEC3F enzyme, an APOBEC3G enzyme, an APOBEC3H enzyme, and an activation-induced cytidine deaminase (AID) enzyme (0034-0038, table 1).
In re claim 29, Mulvey ‘092 teaches wherein the radiotherapy comprises external beam radiation (0124-0126, note that at least the proton therapy is external beam radiation).
In re claim 30, Mulvey ‘092 teaches wherein the radiotherapy comprises brachytherapy (0124).
In re claim 31, Wedekind ‘105 teaches wherein the subject has cancer (0059, 0219, 0222).
In re claim 32, Wedekind ‘105 teaches wherein the cancer is a cancer with elevated APOBEC activity (0051, 0222, 0230, 0250).
In re claim 33, Wedekind ‘105 teaches wherein the cancer is bone cancer, soft tissue cancer, colon cancer, rectal cancer, esophageal cancer, lung cancer, central nervous system (CNS) cancer, breast cancer or uterine cancer (0222).
In re claim 35, Wedekind ‘105 teaches wherein the exogenous cytidine deaminase inhibitor compound is administered to the subject in a pharmaceutical composition, and wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier (0215-0216).
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wedekind ‘105 and Mulvey ‘092 in view of Mckearn et al. (ES 2,232,305, hereinafter McKearn ‘205).
In re claim 23, Wedekind ‘105 fails to teach wherein the therapeutic regimen comprises administering the exogenous cytidine deaminase inhibitor compound to the subject prior to and concurrent with the administered radiotherapy.
Mulvey ‘092 teaches wherein the therapeutic regimen comprises administering the inhibitor compound to the subject radiotherapy (0125), but fails tot each prior to and concurrent with the administered radiotherapy.
McKearn ‘205 teaches wherein the therapeutic regimen comprises administering the inhibitor compound to the subject prior to (English translation, page 18, para 1) and concurrent with the administered radiotherapy (English translation, page 18, paras 1-2; page 19, paras 3)
It would have been prima facie obvious to one of ordinary skills in the art at the time of invention to modify the method/device of Wedekind ‘105 to include the features of Mulvey ‘092 in order to enhance the sensitivity of the tumor cells to the particular therapeutic agent, and to include the features of McKearn ‘205 in order to achieve an improvement in the quality of life of a patient undergoing cancer treatment Other beneficial effects of reduction of the incidence of adverse effects.
Response to Arguments
Applicant's arguments filed on August 11, 2026 have been fully considered but they are not persuasive.
In response to Applicant’s argument that “[[a]] skilled person would recognize that an exogenous TAP inhibitor and an exogenous cytodine deaminase inhibitor have different targets (TAP vs cytidine deaminase inhibitor respectively) and there is no real connection between TAP and cytidine deaminase. It cannot be assumed that any exogenous inhibitor regardless of its target can be combined with radiotherapy to increase the therapeutic benefits. Furthermore, none of Wedekind '105 and Mulvey '092 has established a relationship between cytidine deaminase and cancer nor a relationship between a cytidine deaminase inhibitor and the effectiveness of radiotherapy,” the Examiner disagree. Applicant has failed to provide any factual evidence to support why a skilled person would have such recognition; and therefore such argument is merely Applicant’s personal opinion. They are not persuasive. Furthermore, both references teach an inhibitor, although, it has different composition as in many inhibitor also have different chemical composition, it will well within one of ordinary skill in the art use different inhibitor under the taught condition for doing the similar experiences. Both are exogenouse inhibitor too. Furthermore, Wedekind ‘105 teaches combining with other treatment therapies (0023, 0030, 0039, 0042, 0220), and specifically teaches “combination with chemotherapeutic agents” and “treating a condition, wherein the condition is a cancer.” See para 0220-0222. One of ordinary skill in the art would know that a cancer treatment will involve with radiation, chemo and/or immunotherapy (i.e. chemo can be injected in the body once a week while radiation the body daily, a standard cancer treatment practice to treat the type of cancer listed in para 0222, of course, stage dependent; but at stage 1-3, radiation is used in combination with chemo and/or immunotherapy; and often in treatment and in research radiation is used for stage IV as well. Any licensed medical or radiation oncologist can explain this in detail). Hence, Wedekind ‘105 has taught that the exogenous cytodine deaminase inhibitor can be in combination with cancer treatment. Mulvey ‘092 also teach cancer treatment. Both Wedekind ‘105 and Mulvey ‘092 teaches cancer treatment with overlapping type of cancer targets (see Wedekind ‘105 para 0222; and Mulvey ‘092 para 0118-0120, i.e. breast cancer; liver cancer). Hence, it is obvious to combine with radiotherapy to increase the therapeutic benefits in cancer treatment.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, One of ordinary skill in the art would know that a cancer treatment will involve with radiation, chemo and/or immunotherapy (i.e. chemo can be injected in the body once a week while radiation the body daily, a standard cancer treatment practice to treat the type of cancer listed in para 0222, of course, stage dependent; but at stage 1-3, radiation is used in combination with chemo and/or immunotherapy; and often in treatment and in research radiation is used for stage IV as well. Any licensed medical or radiation oncologist can explain this in detail). Hence, Wedekind ‘105 has taught that the exogenous cytodine deaminase inhibitor can be in combination with cancer treatment. Mulvey ‘092 also teach cancer treatment. Both Wedekind ‘105 and Mulvey ‘092 teaches cancer treatment with overlapping type of cancer targets (see Wedekind ‘105 para 0222; and Mulvey ‘092 para 0118-0120, i.e. breast cancer; liver cancer). Hence, it is obvious to combine with radiotherapy to increase the therapeutic benefits in cancer treatment.
In response to Applicant’s argument that “Applicant contends that there is no expectation of success to combine radiotherapy with the cytidine deaminase inhibitor as recited in the instant claims in view of Mulvey '092 and Wedekind '105,” the Examiner disagrees. Applicant has failed to provide any factual evidence to rebut this. And this is merely Applicant’s opinion. And there is reasonable expectation of success to combine radiotherapy with inhibitors as shown by Mulvey ‘092 as explained above. It is reasonable to make use of a different type inhibitor that also is taught be used as chemo or immunotherapy to treat cancer as show above. Hence, there is a reasonable expectation of success.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 BO JOSEPH PENG whose telephone number is (571)270-1792. The examiner can normally be reached Monday thru Friday: 8:00 AM-5:00 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ANNE M KOZAK can be reached at (571) 270-0552. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BO JOSEPH PENG/Primary Examiner, Art Unit 3797
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