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
Examiner acknowledges that, according to the Filing receipt received 01/30/2025, that the instant application 18/724,480 filed 06/26/2024 is a 371 of PCT/US2023/060714 filed 01/17/2023, which claims domestic benefit of U.S. provisional applications 63/268,690 filed 02/28/2022 and 63/266,867 filed 01/18/2022.
However, the limitations of the instant claims 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 63/268,690 (“the ‘690 provisional”) or 63/266,867 (“the ‘867 provisional”). More specifically, the limitations of Formula (A-I), wherein X and/or Z are C(R7R8) are not taught or suggested in their entirety. In the ‘690 provisional, the disclosure is only so broad as to teach or suggest a compound of Formula (A) wherein the atoms in the X and Z position are O and R3a and R4a can be independent substituents or form a double bond together. In the ’867 provisional, the disclosure is only so broad as to teach or suggest a compound of Formula (I) wherein the atoms in the X and Z position are O and the carbons to which R3 and R4 are attached are doubly bound. Neither provisional teaches or suggests a compound or genus of compounds wherein X and/or Z can be carbon. Other deficiencies may also be present. As such, all the instant claims have been awarded the effective filing date of PCT/US2023/060714 filed 01/17/2023.
Information Disclosure Statement
The Information Disclosure Statements filed on 09/19/2024 and 01/22/2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full, except where lined through. A signed copy of list of references cited from the IDS is included with this Office Action. Examiner additionally notes that in the 09/19/2024 IDS (9 pages), Cite No. 50 of the non-patent literature documents cites the author as “MARIN ET AL.” which should be “MARIM ET AL.” which has been annotated on the signed copy, and in the 09/19/2024 IDS (7 pages), Cite No. 19 of the non-patent literature documents cites the author as “SILVA ET AL.” which should be “DA SILVA ET AL.” which has been annotated on the signed copy.
Specification
The disclosure is objected to because of the following informalities: on p. 83, Scheme 4, "O2/Co)salen)" should read "O2/Co(salen)".
Appropriate correction is required.
Claim Objections
Claim 14 is objected to because of the following informalities: Claim 14 ends in two periods. 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 10 and 14 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.
Claims 10 and 14 recites the following limitation for R1.
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However, R1 cannot be present if the dashed line represents a double bond, as this would violate the valence of carbon, which can only have four bonds. Correction is required.
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.
Claims 1-3, 5-6, 8-18, 24, 30, 32, 34-38, 41, 46, 49, 54-55, 61, 66, and 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 enantiomers, diastereomers, tautomers, isotopic variants, and pharmaceutically acceptable salts of a compound of claim 1, does not reasonably provide enablement for solvates, hydrates, and/or prodrugs of a compound of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
1) Amount of guidance provided by applicant. Applicant has demonstrated within the application how to make compounds and compositions Formula (A-I). However, the instant specification provides no species of structure (II) wherein solvates, hydrates, or prodrugs are made. The terms “solvates”, “hydrates”, and “prodrugs” are incredibly broad.
As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 “The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However...there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.” The same circumstance appears to be true here. Hence, Applicants must show that solvates, hydrates, or prodrugs of these compounds can be made, or limit the claims accordingly.
2) The nature of the invention and predictability in the art. The invention is directed toward bicyclic quinone compounds. Regarding predictability in the art, chemistry is generally regarded as unpredictable, particularly the formation of solvates and hydrates. Moreover, the term “prodrug” provides no particular guidance as to what structures are encompassed by the instant claims. Additionally see In Re Marzocchi and Horton, 169 USPQ at 367 paragraph 3:
“Most non-chemists would probably be horrified if they were to learn how
many attempted syntheses fail, and how inefficient research chemists are.
The ratio of successful to unsuccessful chemical experiments in a normal
research laboratory is far below unity, and synthetic research chemists, in
the same way as most scientists, spend most of their time working out
what went wrong, and why. Despite the many pitfalls lurking in organic
synthesis, most organic chemistry textbooks and research articles do give
the impression that organic reactions just proceed smoothly and that the
total synthesis of complex natural products, for instance, is maybe a labor-
intensive but otherwise undemanding task. In fact, most syntheses of
structurally complex natural products are the result of several years of
hard work by a team of chemists, with almost every step requiring careful
optimization. The final synthesis usually looks quite different from that
originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who
has experienced for himself the many failures and frustrations which the
development (sometimes even the repetition) of a synthesis usually
implies will be able to appraise such work ......Chemists tend not to publish
negative results, because these are, as opposed to positive results, never
definite (and far too copious)...” Dorwald F. A. Side Reactions in Organic
Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface.
The scope of any compounds, compositions, or pharmaceutically acceptable salts where the variables were not those mentioned above are not adequately enabled or defined. Applicants provide to guidance as how the compounds are made.
3) Number of working examples. The compound core depicted as above represents a genus for which Applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the solvates, hydrates, or prodrugs thereof instantly claimed. Applicant has provided no working examples of any solvates, hydrates, or prodrugs.
Within the specification, “specific operative embodiments or examples of the invention must be set forth, Examples and description should be of sufficient scope as to justify the scope of the claims, Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
4) Scope of the claims. The scope of the claims is all of the thousands of possible compounds represented by general Formula (A-I).
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Given the varying substituent modifications around the core ring structure, the claims are incredibly broad, which is only exacerbated by the claims further reading on solvates, hydrates, and prodrugs thereof.
5) Level of skill in the art. The artisan using Applicant’s invention would be a chemist with a Ph.D. degree and having several years of bench experience.
6) Undue experimentation. MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
The conclusion is clearly justified here that Applicant is not enabled for making these compounds or compositions.
Claim 66 is 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 or alleviating one or more symptoms of a parasitic disease, does not reasonably provide enablement for preventing one or more symptoms of a parasitic disease. 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.
It is presumed “prevention” of the claimed disease would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
The factors to be considered in making an enablement rejection were summarized in the previous rejection. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before the parasitic disease and symptoms thereof occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) The claims are drawn to methods of treatment, prevention, and alleviation. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from parasitic diseases before the fact. 6) The artisan using Applicants invention would be a Board-Certified physician in oncological diseases with an MD degree. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of parasitic diseases. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent parasitic diseases. That is, the skill is so low that no compound effective generally against the prevention of parasitic diseases. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 6, 30, 32, 34, 38, 41, 46, 49, 54, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guzikowski et al. (J. Med. Chem.; 1997; IDS filed 01/22/2026).
Guzikowski et al. discloses the following compounds (p. 2425-2426).
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These compounds are within the scope of Formula (A-I) wherein X and Z are CH2, R5 and R6 are each OH or =O, R1 is absent, R2 is heteroalkyl, R3 and R4 are hydrogen or halogen, and R3a and R4a are hydrogen or form a double bond.
Claim(s) 1-3, 5, 6, 8, 14-15, 24, 30, 32, 34-36, 38, 46, 54, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wulff et al. (J. Org. Chem; 1984; IDS filed 01/22/2026).
Wulff et al. discloses the compounds of the following core structure (p. 2295; Table I).
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Compounds g, s, and u (see Table I) are within the scope of Formula (A-I) wherein X is O or CH2, Z is O or CH2, R1 is absent, R2 is propyl, R3 and R4 are hydrogen, and R3a and R4a are hydrogen.
Claim(s) 1, 3, 6, 30, 32, 34, 38, 46, 54, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry Number 16368-80-2 (CAS; 16 Nov 1984).
Registry Number 16368-80-2 has the following structure.
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The compound is within the scope of Formula (A-I) wherein X and Z are CH2, R5 and R6 are each OH, R1 is absent, R2 is alkyl, R3 and R4 are hydrogen, and R3a and R4a are hydrogen.
Claim(s) 1, 3, 6, 30, 32, 34, 38, 46, 54, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry Number 1223158-34-6 (CAS; 14 May 2010).
Registry Number 1223158-34-6 has the following structure.
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The compound is within the scope of Formula (A-I) wherein X and Z are CH2, R5 and R6 are each =O, R1 is -SO3H, R2 is alkyl, R3 and R4 are hydrogen, and R3a and R4a are hydrogen. Examiner notes that the dashed circle in the structure of Formula (A-I) has been interpreted to have the same meaning as
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.
Claim(s) 1-2, 6, 18, 32, 35-37, 41, 46, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry Number 100972-14-3 (CAS; 22 Mar 1986).
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The compound is within the scope of Formula (A-I) wherein X is O, Z is CH2, R5 and R6 are each =O, R1 is absent, R2 is alkyl, R3a and R3 are alkyl, and R4 and R4a are hydrogen.
Claim(s) 1-2, 5, 8, 17, 30, 32, 34-35, 38, 46, 54, and 61 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar et al. (WO 2014130869 A1).
Kumar et al. discloses the following compound (p. 257).
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The compound is within the scope of Formula (A-I) wherein X and Z are O, R5 and R6 are each OH, R1 is absent, R2 is alkyl substituted by one or more Q, Q is oxo or aryl (phenyl), R3 and R4 are hydrogen, and R3a and R4a are hydrogen.
Examiner’s Note
No claims are allowed. However, claims 11-13, 16, 55, 66, and 71 are free of the art. The closest prior art is of record as above. The prior art does not teach a utility similar in scope to that of the instant invention, such that one of ordinary skill in the art would not be motivated to modify the prior art in order to arrive at additional antiparasitic agents or administer the above compounds to treat a parasitic disease. Examiner additionally notes that the reference US 2019/0343794 A1 (IDS filed 09/19/2024) discloses methods of treating chagas disease comprising administering quinone compounds, but the compounds do not fall within the scope of Formula (A-I).
Conclusion
No claims are allowed.
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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/MADELINE E BRAUN/Examiner, Art Unit 1624 07/06/2026
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