NON-FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Jun. 11, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claims 1-62 have been canceled.
Claims 63, 68, and 70 have been amended and incorporate no new matter.
New claim 71 has been added.
Thus, claims 63-71 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
The information disclosure statement (IDS) submitted on Jun. 11, 2026 was filed after the mailing date of the non-final action on Mar. 11, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
NEW REJECTIONS
Claim Rejections - 35 U.S.C. § 112(b) – Indefiniteness
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 63-71 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: a subject with cancer to whom the compound of formula (I) is administered.
Specifically, independent claim 63 is drawn to a method of treating cancer comprising administering the compound of formula (I), without specifying any subject or patient population to whom the compound is administered, rendering the claims incomplete.
It is suggested to amend claim 1 to, for example: a method of treating cancer comprising administering the compound of formula (I) to a subject or patient in need thereof; i.e., to a cell and/or a living organism having the claimed disease(s), which can be treated by administering the claimed compound, provided such amendment is supported by the disclosure.
Claim Rejections - 35 U.S.C. § 112(a) – Scope of Enablement
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.
Claims 63-71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating renal cancer and melanoma, does not reasonably provide enablement for treating pancreatic neuroendocrine tumors, endometrial cancer, adenoid cystic carcinoma, adrenocortical carcinoma, or bone sarcomas. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
MPEP § 2164.01(a), citing In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), sets out the factors to determine whether experimentation is undue. These factors are applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833,839, 166 USPQ 18, 24 (1970). An analysis of the Wands factors follows.
(A) The breadth of the claims. Claims 63-71 are directed to methods of treating a variety of specific cancers by administering a compound of formula (I) (a.k.a. PM-14 or ecubectedin) or a pharmaceutically acceptable salt thereof. The claimed cancers encompass renal cancers, including renal carcinoma, kidney clear cell carcinoma, and hypernephroma; melanoma and amelanotic melanoma; pancreatic neuroendocrine tumor; endometrial cancer; adenoid cystic carcinoma; adrenocortical carcinoma; bone sarcoma, including chondrosarcoma and myxoid chondrosarcoma; and soft tissue sarcoma, including leiomyosarcoma and liposarcoma, and excluding fibrosarcoma. Thus, the claims encompass treatment of histologically diverse and distinct tumor types which extend well beyond the disclosed working examples.
(B) The nature of the invention. The claims are directed to therapeutic methods whose utility depends on achieving a clinically meaningful anti-tumor effect in a living patient with cancer of specific tissue types. Different tumor types differ in genetic drivers, histology, tumor micro-environment, drug uptake and efflux characteristics, and clinical responsiveness. The activity of a therapeutic agent against one or two tumor types does not reliably predict activity against others, and requires more than a demonstration that the claimed compound is cytotoxic in certain cell lines. The specification itself treats individual cancer types as distinct embodiments rather than as interchangeable members of a single predictable class.
(C) The state of the prior art. Ecteinascidins are potent antitumor agents isolated from the marine tunicate Ecteinascidia turbinata which bind to the DNA minor groove, inducing DNA damage and apoptosis. Synthetic analogues include the claimed compound, ecubectedin (PM-14) and lurbinectedin (PM01183), which are closely similar structural isomers with the same molecular formula, as shown below:
Lurbinectedin (PM01183)
Claimed Formula (I) (Ecubectedin; PM-14)
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223
228
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256
256
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The claimed compound was known in the treatment of certain cancers. For example, Marchante et al. (WO 2018/197663, of record) disclose methods of administering ecubectedin to treat prostate cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, colon cancer, breast cancer, pancreas cancer, sarcoma, ovarian cancer, and gastric cancer (p. 76, line 15 to p. 77, line 4; claims 118-119), as well as fibrosarcoma xenografts in mice (Example 29a).
Marchante et al. also disclose that lurbinectedin has demonstrated a highly potent in vitro activity against solid and non-solid tumor cell lines as well as a significant in vivo activity in several xenografted human tumor cell lines in mice, such as those for breast, kidney and ovarian cancer. PM01183 exerts its anticancer effects through the covalent modification of guanines in the DNA minor groove that eventually give rise to DNA double-strand break, S-phase arrest and apoptosis in cancer cells (p. 3, lines 1-5).
In addition, Elez et al. (2014, cited on PTO-892) disclose a phase I study of lurbinectedin to treat advanced solid tumors, including colorectal cancer, pancreatic cancer, biliary tract cancers, soft tissue sarcomas, soft-tissue synovial sarcomas, and malignant melanoma.
Jimeno et al. (2017, cited on PTO-892) disclose a phase I study of lurbinectedin to treat ovarian carcinoma, soft tissue sarcomas, pancreatic adenocarcinoma, cholangiocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, and synchronic lung and kidney cancer.
Cote et al. (2020, cited on PTO-892) disclose a phase II study of lurbinectedin in metastatic and/or unresectable sarcomas, including leiomyosarcoma; soft tissue sarcomas; synovial sarcoma; malignant peripheral nerve sheath tumor; myxoid liposarcoma; pleomorphic liposarcoma; dedifferentiated liposarcoma; desmoplastic small round cell tumor (DSRCT); undifferentiated pleomorphic sarcoma; myxofibrosarcoma; and follicular dendritic cell sarcoma.
However, the prior art does not disclose methods of administering either ecubectedin (PM-14) or lurbinectedin (PM01183) to treat pancreatic neuroendocrine tumors, endometrial cancer, adenoid cystic carcinoma, adrenocortical carcinoma, bone sarcomas, chondrosarcomas, kidney clear cell carcinoma, hypernephroma, or amelanotic melanoma. Thus, the state of the art does not fill the gaps in the present disclosure.
(D) The level of one of ordinary skill. One of ordinary skill in the art would be an oncologist or cancer pharmacologist with experience in preclinical models and early-phase clinical development of cytotoxic agents. However, high skill cannot substitute for missing data and guidance relating to the specifically claimed cancer types. Even a highly skilled artisan cannot reliably extrapolate from activity in renal and melanoma models and a mixed Phase I solid tumor cohort to methods of treating each of the additional specific cancers recited by claims 63-71 without further testing.
(E) The level of predictability in the art. Cancer treatment is a highly unpredictable art. Tumor types differ in driver mutations, histology, drug exposure, DNA repair status, and clinical behavior. In vitro potency against one or two cell lines does not reliably predict in vivo or clinical activity against different tissue types. Phase I observations of stable disease in a mixed solid tumor patient population are not a predictable basis for the treatment of each specifically claimed cancer. The specification does not identify a structural or mechanistic feature that would make activity across all the claimed cancers reasonably predictable.
(F) The amount of direction provided by the inventor and existence of working examples.
The specification discloses in vitro antiproliferative data and a xenograft model showing tumor volume reduction and survival benefit in a renal carcinoma model; in vitro activity in melanoma cell lines; and a phase I dose-finding study in patients with various advanced solid tumors, from which recommended doses and schedules were derived. The specification also reports stable disease in a limited number of patients with certain other histologies and a general statement that the claimed compound can be used to treat a laundry list of cancers.
A phase I study in mixed solid tumors is designed to evaluate safety, pharmacokinetics, and recommended dose; it is not an efficacy study powered or controlled to establish that the compound treat each of the specific cancers now claimed. Isolated observations of stable disease in a few patients of a given histology do not constitute working examples. The specification does not provide cell-line panels, xenograft models, dose-response data, or other guidance for treating specific cancers beyond renal cancer and melanoma.
(G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. To practice the non-enabled scope, a skilled artisan would need in vitro testing in relevant models of those cancers, in vivo efficacy studies, and clinical evaluation to determine whether the claimed compound would be effective to treat the specifically claimed cancers. The claims are broad relative to the working examples; the art is highly unpredictable; and the prior art does not disclose treatment of the unsupported cancers with the closest analog, lurbinectedin. While the claims are enabled for methods of administering the claimed compound to treat melanoma and renal cancer, they are not enabled for methods of treating the other specific cancers claimed. Thus, the specification fails to disclose how to practice the claimed invention commensurate in scope with the claims without undue experimentation.
Applicant may overcome this rejection by, for example, amending the claims to limit the cancers treated to those supported by the working examples (renal cancer and melanoma); or by presenting evidence that one of ordinary skill in the art could practice the full scope of the claims without undue experimentation.
CONCLUSION
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA E. TOWNSLEY/Examiner, Art Unit 1629
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