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 .
Priority
The present application is the U.S. National Stage Application, pursuant to 35 U.S.C.371, of PCT International Application No. PCT/US22/14379, filed January 28, 2022, which claims priority to U.S. Provisional Application No. 63/144,690, filed February 2, 2021.
Status of the Claims
Claims 1, 2, 4-11, 13-18, 26, 27, 29, and 33 are pending and are examined on their merits.
Claim Objections
Claim 29 is objected to for being a claim that depends from itself. For the purpose of examination, claim will be interpreted as depending from claim 26. 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.
Claim 1 and its dependent claims 5, 7, 9, 11, 17 and 18; claim 2 and claim 33 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 applicant purports to have invented a method for treating cancer, or a related disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising methylenediamine (diaminomethane), or a pharmaceutically acceptable form thereof.
Claim 1 and each of the dependent claims are indefinite for reciting the phrase “related disease or condition”. Specifically, the applicant defines the terms “disease", "disorder" or "condition", in the Specification [0027], as terms “that are used interchangeably herein to refer to a pathological condition, for example, one that can be identified by symptoms or other identifying factors as diverging from a healthy or a normal state. The term "disease" includes disorders, syndromes, conditions, and injuries. Diseases include, but are not limited to, proliferative, inflammatory, immune, metabolic, infectious, and ischemic diseases.”
One of ordinary skill in the art cannot reasonably determine the metes and bounds of the limitation of described by the applicant as “disease", "disorder" or "condition" that deviates a healthy or normal state; caused by disorders, syndromes, conditions, and injuries because the variety of ailments that are met by the criteria outlined above is vast (e.g. fibromyalgia, broken bone, rheumatoid arthritis or PTSD).
Claim 2 applicant purports to have invented a method for reducing the risk of or delaying recurrence of cancer after remission or surgery, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising
methylenediamine (diaminomethane), or a pharmaceutically acceptable form thereof.
Claim 2 is indefinite for reciting the phase “reducing the risk of or delaying recurrence of cancer after remission or surgery”. The only significant reference to the terms reducing or delaying (with the exception of the reiteration of the instant claim) is in [0039]; that in part states: “the terms "treatment" or "treating" a disease or disorder refers to a method of reducing, delaying or ameliorating such a condition, or one or more symptoms of such disease or condition, before or after it has occurred.”
One of ordinary skill in the art cannot reasonably determine the metes and bounds of the limitation described by the applicant as “reducing the risk of or delaying recurrence of cancer after remission or surgery”, because the variation in the response to the treatment can only be measured in a single patient that has either in remission or in a post operative condition and in remission. Determining the reduction of risk or delaying the recurrence of cancer is impossible to determine in a single patient that cannot be simultaneously treated with the compound and not treated with the compound.
Claim 33 applicant purports to have developed a kit comprising a unit dosage form of claim 29 and a dosage unit form of a second therapeutic agent and instructions for
administration thereof.
Claim 33 is indefinite for reciting a “second therapeutic agent”. The only mention by the applicants to a kit is in the specification [0077], that is a reiteration of the instant claim. The agents listed as secondary therapeutic agents are listed in [0067-0069] and included in order of description, a small molecule agent, a protein or antibody or a cell therapy or a second therapeutic agent (e.g., chemotherapy, hormone therapy, radiation therapy, or
immunotherapy agents) as in [0081].
One of ordinary skill in the art cannot reasonably determine the metes and bounds of the limitation described by the applicant as a “second therapeutic agent” because the second therapeutic agent includes every known modern approach to 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.
Enablement
Claim 1 and its dependent claims 5-11, 13-18, 26-29 and 33, claim 2 and claim 4 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The breadth of claims are “a method for treating cancer, or a related disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising methylenediamine (diaminomethane).” The method is further defined as reducing the risk or delaying the recurrence of cancer after remission or surgery, treating a solid tumor, in cancers including lung cancer, liver cancer, skin cancer, ovarian cancer, prostate cancer, breast cancer and blood cancers including leukemia, lymphoma and myeloma, with a second known therapeutic for cancer treatment including with one or more of chemotherapy, hormone therapy, radiation therapy, and immunotherapy. There is no reasonable expectation that the treatment of all cancers can be accomplished by the action of a single drug and the applicant is using know anticancer therapeutics with no evidence that the compound works alone or with any other anticancer agents, thus the applicant has failed to enable the breadth of the claims.
The nature of the invention, level of one of ordinary skill, and state and predictability in the art
The invention relates to the treatment of cancer or a related disease in a subject via the administration of methylenediamine (diaminomethane) and the coadministration of known anticancer drugs to treat solid tumor-related cancers and blood-related cancers. According to the MSDS, found in ChemicalBook (Revision Date:2026-01-03 Revision Number:1), the relevant identified use of the compound of methyenediamine dihydrochoride is for use as a compound for R&D use only, not for medicinal, household or other use. Further, the first aid measures of section 4 in the same document state, if inhaled, or if breathed in, move person into fresh air. If not breathing, give artificial respiration, in case of skin contact; wash off with soap and plenty of water, in case of eye contact, flush eyes with water as a precaution and, if swallowed, never give anything by mouth to an unconscious person. Rinse mouth with water. In the art of cancer medicine, one of ordinary skill in the art would be an oncologist, with several years of specialization beyond medical school. While a typical oncologist would be considered an expert in the field, this factor is outweighed by the state and unpredictable nature of the art. For example, Golub1 establishes that different cancers follow different clinical courses, and thus necessitate different therapies. Golub also shows that the boundaries between different classes of cancer are not always clear, which introduces a need for constant re-evaluation of therapies as more information is learned over the course of a treatment regimen. That is to say, by its nature the art of cancer treatment is unpredictable and constantly changing, and no one treatment option can be expected to work for all forms of cancer.
The existence of working examples
The applicant fails to provide any working examples demonstrating the treatment of cancer, or a related disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising methylenediamine (diaminomethane), (as in claim 1). The list of cancers identified (as in claim 8 and 10) are vast and are general terms used to identify very commonly known cancers. The applicant has no working examples of treating a “related disease or condition” in a subject using the described methods, and does not show, either by example or reference that a pharmaceutical composition comprising methylenediamine (diaminomethane) is useful for either the treatment of cancer or a disease related to cancer.
Applicant’s working examples amount to cell viability assays using a commercially available apoptosis kit purchased from the supplier Invitrogen; intended to demonstrate the ability of any compound to kill the targeted cells of the assay. According to the results listed in the specification, methylenediamine (diaminomethane) clearly kills cells. Although, they also describe a mouse model subcutaneously inoculated with liver cancer cells and treated with 120 mg/Kg and 240 mg/Kg of Methylenediamine (dihydrochloride salt) and show that the higher dose appears more effective at reducing tumor size, they do not enable it to be practiced on a related disease or condition, unless the compound kills cells indiscriminately.
The amount of direction provided and quantity of experimentation needed
The applicant has failed to describe the related disease or condition to be treated with methylenediamine (diaminomethane), but goes to great length to describe the cancers to be treated including: lung cancer, liver cancer, skin cancer, ovarian cancer, prostate cancer, breast cancer and blood cancer. Even though the applicant has “evaluated” the compound in cancer cell lines and a murine model they have not shown the cellular mechanism of action and have not performed the requisite pharmacokinetic evaluations to prove the effectiveness of the compound. For example, Brooks, et. al., Applicability of drug response metrics for cancer studies using biomaterials, Phil. Trans. R. Soc. B 374: 2018, 0226, describes the pharmacology metrics associated with the evaluation of the activity of potential drug for use as a therapeutic.
“Pharmacology metrics, such as IC50 (the inhibition concentration of a drug where the response is reduced by half), EC50 (the effective concentration of a drug that gives half-maximal response) and Emax (the drug’s maximum effect), have been used to evaluate the results of drug response assays and describe drug potency. Recently, Hafner et al. [1] defined the GR50: the concentration of a drug that reduces cell growth rate by half. The GR50 is an important contribution to the field of drug screening, because it accounts for the variable differences in growth rates between different cell lines.”
Brooks, Introduction, paragraph 1 (emphasis added).
Applicant has not performed the any of the pharmacology metrics as outlined by Brooks, to evaluate the effectiveness of the compound intended to be administered to subjects, further the quantity of experimentation necessary to establish the effectiveness of methylenediamine (diaminomethane) for use as an anticancer active compound alone or with other proven anticancer therapeutics requires significantly more experimentation to establish the IC50, EC50, Emax and GR50 of the core compound and to evaluate the interaction of the compound with other proven anticancer therapeutics interaction of the compound with other values as identified by Brooks.
Conclusion
Claims 1, 2, 4-11, 13-18, 26, 27, 29, and 33 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL RANDALL GAUGER whose telephone number is (571)272-1325. The examiner can normally be reached M-F 7:30-5:00.
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, Jeffery 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PAUL RANDALL GAUGER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Golub et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999 Oct 15;286(5439):531-7. doi: 10.1126/science.286.5439.531. PMID: 10521349