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 instant application, filed 04/04/2022, is a Continuation of PCT/US2020/054134, filed 10/02/2020, which claims domestic priority to U.S. Application No. 62/910,278, filed 10/03/2019.
Preliminary Amendments and Claim Status
The preliminary amendment filed on 10/15/2025 is acknowledged and entered.
Claims 1, 6-9, 10, 12, 13, 15-19 are amended;
Claim 14 is cancelled;
Claims 1-13 and 15-27 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 02/02/2024, 08/20/2024, 01/02/2025, and 10/15/2025 are acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election without traverse of Group I (claims 1-13, 15-19 and 24) drawn to a compound of formula (I), and compound I-20 (Example 35) as a species of a compound of formula (I) in the reply filed on 10/15/2025 is acknowledged.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made FINAL.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species (Figure 1) makes a contribution over the prior art of record. Therefore, according to MPEP 803.02: should the elected species appear allowable, the search of the Markush-type claim will be extended. The Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration. It has been determined that the entire scope claimed is not patentable.
Figure 1. Elected Species
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Figure 1. 5-fluoro-N-hydroxy-6-((1-(pyridin-3-yl)cyclopropyl)amino)nicotinamide
Status of Claims
Claims 1-13 and 15-27 are pending in the instant application. Claims 2, 11, 13, 16-23, and 25-27 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 1, 3-10, 12, 15, and 24 read on an elected invention and species and are therefore under consideration in the instant application.
Specification Objection
The disclosure is objected to because of the following informalities:
It is evident that within the specification (pages 22-26) that multiple different programs have been used to generate chemical structures. There is little uniformity within the way the structures have been drawn, and sometimes, it is very difficult to ascertain which substituents have been placed, due to low resolution used. For example, on page 23, lines 1-5:
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In some two-dimensional representations of the structures, it is clear that a Fluorine substituent is present, because it is very clearly legible, such as in the structures printed on lines 2 and 5. However, because of the different fonts and representations used, it is not entirely clear that Fluorine is present as a substituent, for example in the compounds of lines 1, 3, and 4. It is imperative that all structures are legible, and uniformly generated for consistency purposes.
Appropriate correction is required.
Claim Objections
Claims 6 and 12 are objected to because of the following informalities:
Regarding claim 6, the claim recites “pyrimidinyl, pyridinyl, pyridazine, and pyrazine.” Applicant has used both substituent and molecular naming to define the same substituent, and this naming is inconsistent. The claim should recite either “pyrimidinyl, pyridinyl, pyridazinyl, and pyrazinyl” or “pyrimidine, pyridine, pyridazine, and pyrazine.”
Regarding claim 12, it is evident that within the claim that multiple different programs have been used to generate chemical structures. There is little uniformity within the way the structures have been drawn, and sometimes, it is very difficult to ascertain which substituents have been placed, due to the size and resolution of the two-dimensional structures used. For example: on pages 4 and 5 of the instant claims filed 10/15/2025, applicant recites:
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In several representations it is very difficult to ascertain the exact chemical substituents drawn. For example, in some representations, it is clear that a Fluorine substituent is present, while in others, it is very difficult to ascertain. The only compound which is satisfactory, and fully legible of the example compounds included above, is the last structure reproduced. It is imperative that all structures be legible, and uniformly generated for consistency purposes and to avoid confusion.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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, 3-10, 15, and 24 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. § 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 3-10, 15, and 24 of the instant application are drawn to compounds having following substituents:
R2 and R3 are H, halogen, alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —(CH2)-carbocyclyl, —(CH2)-heterocyclyl, —(CH2)-aryl, and —(CH2)-heteroaryl (see instant claim 1)
R4 and R4′ are H, alkyl, —CO2-alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —(CH2)-carbocyclyl, —(CH2)-heterocyclyl, —(CH2)-aryl, and —(CH2)-heteroaryl; or R4 and R4′ taken together with the carbon atom to which they are attached form a carbocyclyl or heterocyclyl (see instant claim 1)
wherein each alkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from the group consisting of halogen Fluoro, haloalkyl, oxo, hydroxy, alkoxy, —OCH3, —CO2CH3, —C(O)NH(OH), —CH3, morpholine, and —C(O)N-cyclopropyl (see instant claim 1)
R1 is a heteroaryl selected from the group consisting of pyrimidinyl, pyridinyl, pyridazine, and pyrazine (see instant claim 6)
R2 and R3 are independently selected from the group consisting of H, F, C1-6 alkyl, C3-6 cycloalkyl, —(CH2)—C3-6 cycloalkyl, 4- to 6-membered heterocyclyl, and —(CH2)-(4- to 6-membered heterocyclyl) (see instant claim 8)
35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of compounds having the following claimed substituents:
R2 and R3 as halogen, heteroaryl, —(CH2)-carbocyclyl, —(CH2)-heterocyclyl, —(CH2)-aryl, and —(CH2)-heteroaryl;
R4 and R4′ as alkyl, —CO2-alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —(CH2)-carbocyclyl, —(CH2)-heterocyclyl, —(CH2)-aryl, and —(CH2)-heteroaryl; or R4 and R4′ taken together with the carbon atom to which they are attached form a carbocyclyl or heterocyclyl
wherein the substituents on each alkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are defined as Chloro, Bromo, Iodo, oxo, hydroxy, alkoxy, and —C(O)NH(OH);
R1 as pyridazine, and pyrazine
R2 and R3 as F, C3-6 alkyl, C5-6 cycloalkyl, —(CH2)—C3-6 cycloalkyl, 5- to 6-membered heterocyclyl, and —(CH2)-(5- to 6-membered heterocyclyl);
The instant specification (pages 45-50) teaches compounds which are characterized as having only the following substituents:
R2 and R3 are H, alkyl, carbocyclyl, heterocyclyl, aryl
R4 and R4′ are H
wherein the substituents on each alkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are Fluoro, haloalkyl,—OCH3, —CO2CH3,—CH3, morpholine, and —C(O)N-cyclopropyl
R1 is a heteroaryl selected from pyrimidinyl, pyridinyl
R2 and R3 are H, C1-2 alkyl, C3-4 cycloalkyl, —(CH2)—C3-6 cycloalkyl, 4-membered heterocyclyl, and —(CH2)-(4-membered heterocyclyl)
Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-5, above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 11-15, above).
There are no working examples in the instant specification for the wide range of substituents claimed, but for which evidence of possession has not been provided (see substituents 6-10, above). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gosteli, 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.") Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed compounds as indicated above prior to the effective filing of the instant application. Thus, claims 1, 3-10, 15, and 24 of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
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 12 is 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 12 recites the limitation
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, named Compound I-25 in the instant specification (Table 1, page 46). There is insufficient antecedent basis for this limitation in the claim, for the following reasons. Firstly, claim 12 is a dependent claim which depends on independent claim 1. Within the compound I-25, Y is defined as CR2R3 wherein both R2 and R3 are H, resulting in CH2 at the Y position. However, claim 1 recites “wherein at least one of R2 and R3 is not H,” which prohibits a compound of claim 1 from having CH2 at the Y position. As such, the compound lacks antecedent basis, because R2 and R3 are both H resulting in CH2 at the Y position of Compound I-25, explicitly prohibited by claim 1.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-8, 10, and 15 are rejected under 35 U.S.C. § 103 as being unpatentable over Aurora Fine Chemicals CAS Registry Number: RN 2202159-87-1, [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2202159-87-1;. Entered STN: 30 Mar 2018]. Registry Number 2202159-87-1 is available as prior art as of 30 Mar 2018, the date it was indexed into the REGISTRY database (Figure 2). Registry number 2202159-87-1 renders obvious compounds of Formula (I) wherein:
Figure 2. Structural comparison of prior art compound and instantly claimed Formula (I)
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Figure 2. a) CAS Registry Number: RN 2202159-87-1; b) instantly claimed Formula (I)
n is 0 (see instant claims 1, 3, and 10)
X is NR4, wherein R4 is H (see instant claims 1, 4, 10, and 15)
Y is CR2R3 (see instant claims 1 and 5), wherein R2 is CH3 and R3 is H (see instant claims 1, 8, and 10)
R1 is pyridinyl (see instant claims 1, 6, and 7)
Further regarding claim 15, and a compound of Formula (IIa),
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the prior art compound renders obvious the instant claim wherein,
R2 is CH3
R3 and R4 are H
Z1, Z3, Z4 and Z5 are CR5, wherein each R5 is H
Z2 is N
The prior art compound fails to teach Fluorine at the specified position on the pyridinyl ring. The substituent on the pyridinyl ring in a compound of Formula (I) as claimed is Fluorine, and is Chlorine on the prior art compound.
However, the substitution of Fluorine for Chlorine would result in compounds of similar structure and chemical properties. The courts have determined that such substitutions result in compounds which are considered obvious variants of each other. The courts have stated:
similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close' structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP § 2144.08(d)).
Fluorine and Chlorine are both halogens, having the same number of valence electrons and general electron configurations. Therefore, a person of ordinary skill in the art prior to the effective filing date of the instantly claimed compounds, would be motivated to make the Chlorine to Fluorine halogen substitutions in the instantly claimed compounds, as the resulting compounds would have similar chemical properties, and the substitutions are well-known in the art to be modulators of chemical affinity. Thus, substitutions for Fluorine in the instant application by Chlorine found in the prior art are considered obvious.
See MPEP § 2128 “Printed Publications” as prior art. An electronic publication, including an on-line database or Internet publication, is considered to be a “printed publication” within the meaning of 35 U.S.C. § 102 (a) and (b) provided the publication was accessible to persons concerned with the art to which the document relates. In re Wyer, 655 F.2d 221, 227, 210 USPQ 790, 795 (CCPA 1981): since this date represents the date that each compound entered the REGISTRY database on STN, this represents the date that each compound was made accessible to the public.
It is further noted that for the purposes of determining if a reference is a “printed publication,” MPEP § 2128 (I) states the following:
A reference is proven to be a "printed publication" "upon a satisfactory showing that such document has been disseminated or otherwise made available to the extent that persons interested and ordinarily skilled in the subject matter or art, exercising reasonable diligence, can locate it." In re Wyer, 655 F.2d 221, 210 USPQ 790 (CCPA 1981) (quoting I.C.E. Corp. v. Armco Steel Corp., 250 F. Supp. 738, 743, 148 USPQ 537, 540 (SDNY 1966)) ("We agree that ‘printed publication’ should be approached as a unitary concept.
where “prior art disclosures…on an on-line database are considered to be publicly available as of the date the item was publicly posted.” Since each of the database entries above lists the date that each compound was entered into the on-line database, the compounds were made publicly available as of that date in each citation, and are available as prior art disclosures to the public. As such, the instant claims are rendered obvious.
Correspondence
No claim is allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623