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
The amendments received 07/07/2026 have been entered. Claims 1-13 and 16-18 are pending. Any objection or rejection previously set forth in the Office Action mailed 11/28/2025 has been overcome by amendment and is withdrawn.
New grounds of rejection are set forth herein as necessitated by amendment.
Priority
Examiner acknowledges that, according to the Filing receipt received 06/25/2024, that the instant application 18/349,256 filed 07/10/2023 is a CON of PCT/US2022/070126 filed 01/10/2022, which claims benefit of U.S. provisional application 63/135,370 filed 01/08/2021. Claims 1-2, 5-6, and 16 have been awarded the effective filing date of 01/08/2021.
However, the limitations of claims 3-4, 7-13, and 17-18 are not adequately supported or enabled in the manner provided by 35 U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by 63/135,370. More specifically, the limitations of HydroxyUreaMethyl Acylfulvene combined with the agents listed in instant claims 3 and 4, and treating a subject with a cancer with high PTGR1 expression and/or a level of expression of PTGR1 that is sensitive to HydroxyUreaMethyl Acylfulvene (let alone SEQ IDs 1-4) are not taught or suggested in their entirety by 63/135,370. Other omissions may also be present. As such, claims 3-4, 7-13, and 17-18 have been awarded the effective filing date of PCT/US2022/070126 filed 01/10/2022.
Claim Objections
Claims 1 and 17 are objected to because of the following informalities:
Claim 1: “whereinthe” should read “wherein the”;
Claim 17: “determin” should read “determine”.
Appropriate correction is required.
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 1-13 and 16-18 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.
Claim 1 recites “the selected subject”. This term lacks antecedent basis. Claims 2-13 and 16-18 do not clarify the limitation at issue and are similarly rejected.
Claim 16 recites “the threshold for” and “the HydroxyUreaMethyl Acylfulvene sensitivity”. These limitations lack antecedent basis, as claim 16 depends on claims 1 and 15, but claim 1 does not refer in any way to determining a subject’s sensitivity to HydroxyUreaMethyl Acylfulvene or a threshold.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS/BRENDA L COLEMAN/ Primary Examiner, Art Unit 1624 —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 16 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 16 depends on claim 1 or 15. Claim 15 has been cancelled. Claim 16 therefore fails to further limit or incorporate the limitations of a claim upon which it depends.
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 § 112(a)
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.
Claim 17 is 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.
Claim 17 has been amended to recite “one or more reagents configured to measure expression or transcription of PTGR1 in the specimen”. The disclosure at the time of filing does not disclose or suggest a reagent “configured to measure expression or transcription of PTGR1 in the specimen”. There is additionally no guidance set forth regarding what reagents, or how the reagents, are configured to carry out this function. This limitation is considered new matter as it lacks support in the disclosure at the time of filing. Correction is required.
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) 3-4, 7-10, and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kulkarni et al. (Oncotarget; published 13 April 2021; previously cited). Claims 3-4, 7-10, and 12 have bee awarded the effective filing date of 01/10/2022.
Kulkarni et al. discloses a method of inhibiting the growth of in vitro models of brain metastases originating from primary lung cancers, comprising contacting cell lines with LP-184 (p. 801). Kulkarni et al. discloses that LP-184 has the following structure (Supplementary Figure 1).
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Kulkarni et al. additionally discloses using a 3D model to determine cell line sensitivity to LP-184 (p. 802). Kulkarni et al. teaches that PTGR1 is likely to be a primary causal determinant underlying LP-184 sensitivity prediction, wherein PTGR1 gene expression is significantly correlated with LP-184 sensitivity (p. 799, col. 1). Kulkarni et al. teaches that temozolomide and radiation are used to treat brain tumors and/or metastases (p. 793, col. 1; p. 799, col. 2). Kulkarni et al. also discloses that LP-184 can cross the blood brain barrier and is a promising candidate as a novel treatment for brain metastases (p. 799, col. 1).
While Kulkarni et al. does not specifically teach a method of treating a metastasized brain or CNS tumor in a subject, it would be prima facie obvious for one of ordinary skill in the art to administer LP-184 to a subject in need thereof. One would have been motivated to do so, with reasonable expectation of success, as Kulkarni et al. suggests that LP-184 could be used for patient treatment and demonstrates its in vitro efficacy and its ability to cross the blood brain barrier.
It would be prima facie obvious for one of ordinary skill in the art to combine the optically negative isomer of HydroxyUreaMethyl Acylfulvene of Kulkarni et al. with radiation and/or temozolomide. One would have been motivated to do so, with reasonable expectation of success, as radiation and temozolomide are both standard therapies for the treatment of brain cancers, and one would be apprised that combining agents/treatments known to treat the same disease could yield an improved effect or tumor response.
It would be prima facie obvious for one of ordinary skill in the art to identify and treat a patient with LP-184 based on PGFR1 expression. One would have been motivated to do so, with reasonable expectation of success, as Kulkarni et al. teaches that LP-184 sensitivity and PTGR1 expression are significantly correlated, and Kulkarni et al. discloses known methods of determining PTGR1 expression.
Claim(s) 11, 13, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kulkarni et al. (Oncotarget; published 13 April 2021; previously cited) as applied to claims 3-4, 7-10, and 12 above, and further in view of Kelner (US 20220040191 A1; effectively filed 2019; previously cited).
Kulkarni et al. disclose as above, but do not teach that the sequences of the PTGR1 gene or protein of claims 11 and 13, respectively. This limitation is obvious over Kelner.
Kelner teaches nucleic acid sequence SEQ ID NO: 249 and amino acid sequence SEQ ID NO: 250 (see sequence listing), which are identical to the instant SEQ ID NO: 4 and SEQ ID NO: 3. Kelner teaches that these sequences encode PTGR1 and are biomarkers of cancers sensitive to illudofulvene treatment (Abstract, par. [0042]). Kelner et al. additionally discloses kits for determining PTGR1 expression relative to standards and determining cell sensitivity to illudofulvenes (par. [0137]).
It would have been prima facie obvious for one of ordinary skill in the art to use the above sequences in the method of determining PTGR1 expression. One would have been motivated to do so, with reasonable expectation of success, as these biomarkers are known in the art to indicate sensitivity to illudofulvenes which are similar in function to the compound of Kulkarni et al.
Response to Arguments
Applicant's arguments filed 07/07/2026 have been fully considered but they are not persuasive.
Regarding the rejection under 35 U.S.C. 103 over Kulkarni et al. (Oncotarget; 2021), Applicant argues that the article “reports in vitro models and does not disclose the claimed clinical method…” (p. 12 of Remarks). This is not persuasive. As stated in the rejection, while the in vitro models disclosed by Kulkarni et al. do not explicitly teach the claimed method in a subject, “it would be prima facie obvious for one of ordinary skill in the art to administer LP-184 to a subject in need thereof. One would have been motivated to do so, with reasonable expectation of success, as Kulkarni et al. suggests that LP-184 could be used for patient treatment and demonstrates its in vitro efficacy and its ability to cross the blood brain barrier.” Moreover, it would be understood that treating a brain metastasis in a subject with primary lung cancer would necessarily require diagnosis before the fact.
Furthermore, Examiner addresses obviousness of determining PTGR1 expression in the above rejection, “One would have been motivated to do so, with reasonable expectation of success, as Kulkarni et al. teaches that LP-184 sensitivity and PTGR1 expression are significantly correlated, and Kulkarni et al. discloses known methods of determining PTGR1 expression.”
Applicant’s statement that the article “does not disclose the claimed clinical method” is merely conclusory but does not address the arguments made by Examiner as to why one of ordinary skill in the art would not find it prima facie obvious to arrive at the claimed invention. As such, the rejections are maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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/M.E.B./Examiner, Art Unit 1624 07/10/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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