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 of Claims
Claim 24-43 are pending.
Priority
Instant application 18/917,773, filed 12/30/2024 claims priority as follows:
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Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 17,286,002, filed on 04/16/2021.
Information Disclosure Statement
All references from IDS(s) received 12/23/2024 have been considered unless marked with a strikethrough.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: Deuterated melflufen compounds for treating cancer.
Claim Rejections - 35 USC § 112
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 24-43 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 treating certain types of cancer (e.g. those listed in claim 39), does not reasonably provide enablement for treating or preventing all diseases or cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), the following factors are considered to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of Formula (I), which are deuterated analogs of the known anti-tumor agent melflufen.
Breadth of the claims:
The claims are broadly directed to the use of the compounds of Formula (I) for the treatment or prevention of any disease or any cancer. Claim 24 does not recite any disease and is being interpreted as encompassing all diseases. Claim 38 recites “treatment or prophylaxis of cancer” and does not specify the particular type of cancer.
Level of ordinary skill in the art:
The artisans using applicant’s method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
For example, different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the cancer involved.
State of the prior art and predictability in the art:
Relevant prior art includes WICKSTROM (Oncotarget, vol. 8, no. 39, June 2017, pp. 66641–55). Wickstrom discloses that melflufen is a peptidase-potentiated alkylating agent (title, abstract). Wickstrom discloses that the activity of melflufen is directed to aminopeptidase N (APN)-expressing cells (page 66642, left side, 2nd para.); and discloses that increased expression of APN has described in cancers characterized by “fast-growing and aggressive phenotypes” (Wickstrom, abstract). Wickstrom therefore provides evidence that melflufen’s efficacy is contingent upon elevated APN expression, and that elevated APN expression is not universal across cancer types.
See also BERGLUND (Investigational New Drugs, vol. 33, no. 6, Dec. 2015, pp. 1232–41). Berlund is drawn to the first in human phase I/IIa clinical study of melflufen to patients with advanced solid tumor malignancies. Berlund discloses that melflufen is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells (title, summary). Berlund discloses that 45 patients received melflufen therapy, and discloses that clinical activity is suggested in ovarian cancer, but modest in the treatment of refractory NSCLC (summary). Accordingly, Berlund provides evidence that melflufen does not work across any cancer type, but is instead only effective for certain types of cancer such as ovarian cancer.
With respect to cancer prevention, see WILLIAM (Nature Reviews Drug Discovery, vol. 8, no. 3, Mar. 2009, pp. 213–25). William is relied upon as evidence that the broad translation of cancer chemoprevention to the clinic is not yet a reality (page 213, abstract); and faces numerous challenges (page 218, “Challenges of chemoprevention”), including the identification of “truly high-risk patients”. Accordingly, William provides evidence that cancer prevention has only been achieved under very specific circumstances in defined high-risk populations.
Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
That a single compound or class of compounds can be used to treat and prevent all diseases and all cancers embraced by the claims is an incredible finding for which applicant has not provided supporting the requisite supporting evidence. Applicant has not provided competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for treating or preventing all cancers and diseases by administering the instant claimed compounds.
The amount of direction provided and working examples:
The only direction or guidance present in the instant specification is the disclosure of cancers applicant considers treatable by the claimed compounds. No working examples of disease treatment are disclosed in the specification. Dose toxicity studies are disclosed in the specification starting at page 30, but these do not constitute working examples of treating or preventing any diseases or cancers.
See MPEP 2164.02 (“Compliance with the enablement requirement of 35 USC 112, first paragraph, does not turn on whether an example is disclosed ... Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”).
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine which particular diseases or cancer types out of all cancers recited would be treated and would furthermore then have to determine which of the claimed compounds in the instant invention would provide treatment of the claimed diseases. They would also need to identify the high-risk patient population to administer the treatment to in order to prevent cancer.
Therefore, in view of the foregoing, claims 24-43 are rejected.
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 24-37 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 24 recites a method for treating a patient comprising administering a “pharmaceutically effective amount” of the compound of formula (I), or a pharmaceutically acceptable salt thereof, to a subject in need thereof. The term “pharmaceutically effective amount” is indefinite and one of ordinary skill in the art would not be reasonably apprised of the scope of the claimed invention.
At page 18, line 26 to page 19, line 2, the Specification states:
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Please note that the phrase “effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. See MPEP 2173.05(c). Here, the effects implied from the specification are numerous and extend to any “therapeutic effect”. Claim 24 does not recite any disease, but simply recites “treating a patient…in need thereof”. Claim 45 is therefore indefinite because it does not clearly state the effect to be achieved. It is unclear what amount(s) of the compound should be administered to render it “effective” because it is unclear which effect(s) the claims are directed to.
Additionally, because no disease is recited in claim 24, the scope of the term “subject in need thereof” is indefinite. It is unclear which subjects fall within the patient population of claim 24. What qualifies a patient as “subject in need thereof” in claim 24? Do they need to have a disease? Can they have any disease, or only a particular kind of disease (e.g. cancer)?
Claims 25-37 depend from claim 24 and fail to resolve the issues identified above. Therefore claims 25-37 are also indefinite.
Claims 40-43 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.
The phrase "for example" renders claims 40-43 indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Therefore, claims 40-43 are rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
US 12,558,337
Claims 24-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,558,337. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘337 patent recite a method for the treatment of cancer selected from the group consisting of multiple myeloma, breast cancer, lung cancer, ovarian cancer, leukemias and lymphomas, comprising administering an effective amount of the pharmaceutical formulation of claim 1; and recite the pharmaceutical formulation of claim 1, wherein the melflufen is OPD-5:
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The claims of the ‘337 patent and the instant claims are therefore directed to common subject matter because the instant claims also recite the above compound (see, e.g., claim 34) in a method for treating cancer including multiple myeloma, breast cancer, lung cancer, ovarian cancer, leukemias, and lymphomas (see, e.g., claim 39).
Conclusion
Claims 24-43 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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