DETAILED ACTION
Claims 1-12, 15-16, 19-20, 25-26, 28, 33, 39, 44, 49, 51, 56, 61, 66, 69 and 72-73, submitted 12 June 2024, are pending in the application and subject to examination in the instant Office 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 .
Claim Objections
Claim 73 is objected to because of the following informalities: dependent claim 73 recites “A bis-besylate salt of Compound 1…”. Claim 73 references a series of compounds of the instant claims in an inconsistent manner. For example, claim 1 is drawn to the compound of Formula I and claim 73 references Compound 1 for the same compound. Applicant could overcome this objection by amending instant claim 73 to be consistent with the terminology of the remainder of the claim set. Appropriate correction is required.
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 1-12, 15-16, 19-20, 25-26, 28, 33, 39, 44, 49, 51, 56, 61, 66, 69, and 72 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 the process of preparing a compound of Formula I or a salt, solvate, hydrate, enantiomer, or mixture of enantiomers, does not reasonably provide enablement for the compound of Formula I wherein the compound is an isotopologue. 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 the invention commensurate in scope with these claims.
Breath of the Claims
Claim 1 recites “A process for preparing a compound of Formula (I): or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof…”. The instant claim is not drawn to any isotopologue in particular, thus can be interpreted to encompasses all isotopologues.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to a compound of Formula (I), a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof.
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to those in the art at the time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc. v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enabled requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
Sib et al. ("Method development and syntheses examples of isotopically labeled compounds to foster operational excellence in pharma industry." Synlett 35.19 (2024): 2155-2173.) teaches many methods of synthesis of isotopic compounds. With regards to 14C synthesis, Sib states “Its superior stability comes with a price though, as the installation of the label mostly includes a multistep synthesis and high costs of starting material” (pg. 2168, Section “Challenges in 14C-synthesis Projects”, Left Col., 1st paragraph). Additionally, Sib teaches where similar compounds, AVE2268 and AVE8887, despite their similarity, required labeling through two different methods. Sid states “For AVE2268, a five-step synthesis was used” (pg. 2168, Section “Challenges in 14C-synthesis Projects”, Left Col., 3rd paragraph) and “Unfortunately, this route was not applicable to AVE8887 and a new route was developed” (pg. 2169, Section “Challenges in 14C-synthesis Projects”, Left Col., 1st paragraph). Thus, this gives credence to the unpredictability in precursor reactions within isotopic chemistry. That is to say that a reaction that works for one precursor compound will not work for all precursor compounds.
Isotopic labeling is known to be a specialized art found in the pharmaceutical industry requiring careful design and performance of synthesis. Elmore et al. ("Isotope chemistry; a useful tool in the drug discovery arsenal." Bioorganic & medicinal chemistry letters 25.2 (2015): 167-171.) teaches that “Isotope Chemistry (IC) is a specialty function found in many large pharmaceutical companies” (pg. 167, Section “Introduction”, Left Col., 1st paragraph). Elmore goes on to recite “When outsourcing a synthesis, a full proposed reaction scheme is provided as a minimum, and typically full experimental details for the non-radioactive reactions. In addition, advanced intermediates are often provided for use in the synthesis and to serve as reference standard” (pg. 168-169, Section “Introduction”, Right Col. and Left Col., 5th and 1st paragraphs, respectively). Due to the specialized nature of isotopic chemistry, it would follow that not all precursor compounds would have similar reactions under identical reaction conditions. The specification merely suggests the preparation of isotopologue variants of the compound of Formula (I) but does not teach nor suggest how one skilled in the art would perform such an isotopic labeling process. Given the lack of teachings in how to prepare the isotopic labeling and the broadly claimed scope of the instant claim encompassing all isotopologues, it would not be possible for one trained in the art to perform such labeling as a routine process.
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known
the relevant art at the relevant time. Factors that may be considered in determining the
level of ordinary skill in the art may include: (A) "type of problems encountered in the
art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are
made;" (D) "sophistication of the technology; and" (E) "educational level of active
workers in the field. In a given case, every factor may not be present, and one or more
factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121
(Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955,
962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil
Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of
ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art
field with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely
related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount
of guidance or direction” refers to that information in the application, as originally filed,
that teaches exactly how to make or use the invention. The more that is known in the
prior art about the nature of the invention, how to make, and how to use the invention,
and the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the
invention and the art in unpredictable, the specification would need more detail as to
how to make and use the invention in order to be enabling. The scope of the required
enablement varies inversely with the degree of predictability involved, but even in
unpredictable art, a disclosure of every operable species is not required. A single
embodiment may provide broad enablement in cases involving predictable factors, such
as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ
122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA
1971). However, in applications directed to inventions in arts where the results are
unpredictable, the disclosure of a single species usually does not provide an adequate
basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA
1938). In cases involving unpredictable factors, such as most chemical reactions and
physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166
USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide
more objective evidence to support the enablement of the aforementioned claims to
contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor in regards to the currently claimed method of preparation of all compound variants (e.g., all isotopologues) of Formula (I). The unpredictability stems from prior art teaching that not all precursor compounds will react similarly to isotopic reactions under similar conditions.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of
the unpredictability of the art. Given the context and scope of the claims mentioned
above, the inventor failed to provide the necessary amount of direction for one skilled in
the art to adequately use the invention across all suggested utility in the broadly stated
disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant provided certain aspects of the instantly claimed invention. For example, guidance was provided on the synthesis of compounds of Formula (I) wherein the variant is a salt thereof, found in paragraph 258 of the disclosure, a solvate thereof, found in paragraph 257, a hydrate thereof, found in paragraph 269 of the disclosure, or an enantiomer or mixture of enantiomers, found throughout the disclosure. The instant disclosure fails to discuss any isotopologues thereof and as such, the Applicants are not entitled to any and all known or unknown isotopologues.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the
predictability of the art, and the direction provided by the inventor. For one skilled in the
art to practice the invention as disclosed, the artisan trying to practice Applicant’s claimed invention would be required to undertake unduly burdensome activities
including:
Experimentation to show the synthesis of compounds of the application wherein the compounds are isotopologues of a compound of Formula (I).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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