Detailed Action
The present office action is in response to the response filed on 16 Dec 2025.
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, 3-7, 11-13, and 18 of the pending application have been examined on the merits. Claims 2, 8-10, 14-17, and 19-20 are withdrawn (see “Response to Applicant Election” below). Acknowledgement is made of the amendments filed 16 Dec 2025.
Priority
Applicants identify the instant application, Serial #: 17/998,117, filed 07 Nov 2022, as a National Stage Entry of International Patent Application #: PCT/US2021/031606, filed 10 May 2021, which claims priority from U.S. Provisional Application #: 63/022,242, filed 08 May 2020.
Response to Applicant Election
Applicant's election without traverse of pancreatic adenocarcinoma as the species of pancreatic cancer, no additional therapeutic agents, and no additional therapies in the reply filed on 16 Dec 2025 is acknowledged.
Claims 2, 8-10, 14-17, and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species.
Election was made without traverse in the reply filed on 16 Dec 2025.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 18 is rejected under 35 U.S.C. 101 because the claimed invention does not meet the criteria for patent eligible subject matter (determining suitability of a subject with cancer for treatment with a cannabinoid). The claims inform the public of the intent of administering a hydroxyureamethyl acylfulvene only if the expression level of PTGR1 in the sample from the human subject is at least 50% greater than a reference level of PTGR1 from a healthy individual.
The claimed invention also includes the judicial exception of determining suitability of a subject for a treatment. This judicial exception is not integrated into a practical application because it is nothing more than interpreting data and thinking, i.e., measuring and comparing PTGR1 expression in patient samples and making an evaluation of suitability for treatment. There is no post solution activity if the patient is not determined to have increased PTGR1 expression relative to the reference sample.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception when considered separately or together. While the claims lay out a method of treatment if the expression level of PTGR1 in the sample from the human subject is at least 50% greater than a reference level of PTGR1 from a healthy individual, there is no additional information about treatment if the PTGR1 concentration has not met the threshold provided by the limits of the claim and so the claim limitations do not amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 112(b)
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 1, 5-7, 11, and 18 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 claim 1, the phrase “locally advanced unresectable” is unclear. There is no subject for this phrase so a person of ordinary skill in the art would be unsure if this refers to a type of pancreatic cancer or another type of cancer. Applicant may overcome this rejection by amending to clarify what is meant by the above phrase. In the interest of compact prosecution, examiner is interpreting the phrase to refer to pancreatic cancer.
Regarding claim 5, it is unclear what is meant by a “high level” of PTGR1. A person of skill in the art would be unsure how much of an increase is required to reach a “high level” and what exactly is the reference for comparison. The specification offers no definitions that the artisan would be able to glean from to determine what is meant by a “high level” of PTGR1. Applicant may overcome this rejection by amending to clarify what a “high level of PTGR1” means.
Regarding claims 6-7, the limitations of “borderline resectable” in claim 6 and “wherein the pancreatic cancer is Stage I, II, III, or IV” in claim 7 lack antecedent basis. Both claims are dependent on claim 1. Claim 1 limits the pancreatic cancer to metastatic pancreatic cancer or locally advanced unresectable pancreatic cancer, neither of which are borderline resectable. Furthermore, as evidenced by PANCAN (retrieved from https://web.archive.org/web/20190819235044/https://pancan.org/facing-pancreatic-cancer/treatment/treatment-types/treatment-by-stage/, accessed 03/11/2026), locally advanced unresectable tumors and metastatic tumors are classified as Stage III and Stage IV pancreatic cancer, respectively. There is no antecedent basis for “borderline resectable” or “Stage I” or “Stage II” pancreatic cancer in the independent claim. Applicant may overcome this rejection by striking “borderline resectable” from claim 6 and “Stage I, Stage II” from claim 7.
Regarding claim 11, the limitation “wherein the cell is in a subject is an animal” lacks antecedent basis. There is no reference to “the cell” in the independent claim 1 which claim 11 is dependent on. Applicant may overcome this rejection by amending to cancel “the cell” from claim 11. Further, it is unclear what “is in a subject is an animal” means. Applicant may overcome this rejection by clarifying what the phrase “is in a subject is an animal” means.
Regarding claim 18, it is unclear who is being treated with the hydroxyureamethyl acylfulvene in step (c). Steps (a) and (b) clearly reference a subject, but step (c) neglects to inform the artisan where hydroxyureamethyl acylfulvene is being administered. Applicant may overcome this rejection by amending to clarify who is receiving the cancer treatment.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 12 does not further limit claim 1 because claim 12 limits the “subject or mammal” to a human. However, claim 1 already limits the subject to a human subject.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1, 3-7, and 11-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 7,655,695, hereinafter ‘695, in light of Cytion (https://www.cytion.com/AsPC-1-Cells/300158, retrieved 03/13/2026), hereinafter Cytion, and Kim et al. (Cell Oncol, 2014, 37:235-243), hereinafter Kim.
The instant claims are directed towards a method of treating metastatic pancreatic cancer or locally advanced unresectable pancreatic cancer in a human subject in need by administering hydroxyureamethyl acylfulvene (claim 1). Applicant further limits the type of pancreatic cancer Applicant has elected pancreatic adenocarcinoma, no additional therapeutic agents, and no additional therapies in the remarks filed 16 Dec 2025. Applicant further limits the type and stage of pancreatic cancer (claims 3-4, 6, and 7), the levels of PTGR1 in a subject (claims 5 and 18), and whether the treatment is a first-line treatment (claim 13).
The instant specification identifies hydroxyureamethyl acylfulvene as LP-184 and further teaches that hydroxyureamethyl acylfulvene has the following structure (paragraph [0032):
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‘695 teaches Compound 6 which has the following structure (column 9, lines 25-35):
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Compound 6 has the same structure as the instant hydroxyureamethyl acylfulvene. ‘695 teaches treating AsPC-1 pancreatic cancer cell lines with Compound 6 (column 16, lines 47-66). Cytion, cited for evidence, teaches that the AsPC-1 cell line is derived from a human patient with metastatic pancreatic adenocarcinoma (pg. 2). Kim, cited for evidence, teaches that pancreatic cancer has increased PTGR1 and this can be used as a biomarker for cancer (Table S3). ‘695 teaches treating pancreatic cancer in a human subject by administering compounds of the reference, including Compound 6 (column 5, lines 55-59; column 14, lines 30-36; column 19, lines 33-37; and claims 1 and 35-39). Thus, ‘695 anticipates the instant claims.
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.
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, 3-4, 6-7, 11-13, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov ID NCT00003760 (https://clinicaltrials.gov/study/NCT00003760?cond=Pancreatic%20Adenocarcinoma&term=Irofulven&rank=1&tab=researcher, version from 2012-08, accessed 03/13/2026), hereinafter ‘760, further in view of US Patent No. 9,725,769, hereinafter ‘769, Staake et al. (Bioorg Med Chem Lett, 2016, 26:1836-1838; provided in IDS 11/07/2022), hereinafter Staake.
‘760 teaches treatment of stage III or stage IV unresectable adenocarcinoma of the pancreas with irofulven (pgs. 3-4). However, ‘760 does not teach treatment of pancreatic cancer with hydroxyureamethyl acylfulvene.
‘769 teaches that irofulven may be used as a first line cancer treatment (column 25, lines 1-6). ‘769 further teaches teaching a method of comparing a biomarker reference to determine if a patient will be sensitive to irofulven and further that a biomarker of sensitivity is PTGR1 (column 26, lines 13-16 and lines 33-35).
‘Staake teaches Compound 8 (scheme 2), which has the same structure as the instant hydroxyureamethyl acylfulvene:
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Staake teaches that Compound 8 is less toxic than irofulven and can be administered at higher doses.
By following the teachings of ‘760, ‘769, and Staake, a person of ordinary skill in the art would treat stage III or stage IV unresectable adenocarcinoma of the pancreas with irofulven as a first line treatment, as taught by ‘760 and ‘769. The artisan would find it obvious to further test the patient first for elevation expression levels of PTGR1, as taught by ‘769, because PTGR1 indicates that a patient will be sensitive towards irofulven treatment. The artisan would further modify the method to replace irofulven with Compound 8, as taught by Staake. The artisan would be motivated to perform this swap because Compound 8 is less toxic than irofulven and can be administered at higher doses. Thus ‘760, ‘769, and Staake teach all the steps of the instant method and render the claims obvious.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625