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 .
Election/Restrictions
Applicant's election with traverse of Group I (drawn to a compound of Formula (I)), in the reply filed on 03/11/2026 is acknowledged.
Claims 1-30 are pending of which claims 29-30 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 1-28 have been examined on the merits.
Please note, for clarity of the record, on 03/11/2026, Applicant elected the species, Compound I-32; as shown below and recited in claim 12, having the following structure:
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The elected species was searched and determined to be free of the art of record. MPEP §
803.02(III)(C). The search/examination was extended to the non-elected species cited in the § 103 rejections below. The full genus of claim 1 was searched.
Response to argument
Applicant’s election with traverse of Group I in the reply filed on 03/11/2026 is acknowledged. The traversal is on the ground(s) that the Group I and II possess a common special technical feature. Applicant also argues that the amendment to claim 1, excludes a 7 to 10-membered heteroaryl, distinguishes the claimed subject matter from prior art PubChem CID 58935990. Applicant’s argument is not persuasive because PubChem CID 58935990 teaches wherein CyB is a bicyclic indazole ring substituted with an oxo, was based on previous claim set and was proper, regardless of the current amendment. In addition, the newly added prior art cited in the 102 rejection reads within the scope of the amended claim. Furthermore, the restriction wherein regarding Invention Group I and II, Group I is directed to a compound of formula (I); whereas Group II is focused to a method of treating a plasma kallikrein-mediated disease. The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claims 2-5 and 23-26 recite a list of chemical structure without appropriate commas between the items. For clarity and proper interpretation, commas should be inserted to separate each element in the list (e.g., “A, B and C”). Applicant is required to correct the claims by inserting commas between each item in the list.
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 1-28 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.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane), the Federal Circuit noted the importance of an application's disclosure and stated, "the hallmark of written description is disclosure." A disclosure adequately describes an invention when it "reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Id. at 1351. "A 'mere wish or plan' for obtaining the claimed invention is not adequate written description." Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement "varies with the nature and
scope of the invention at issue, and with the scientific and technologic knowledge already in
existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Federal Circuit
explained what is required to meet the written description requirement in Ariad Pharm., Inc. v.
Eli Lilly & Co.:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F .3d 1349, 1357-58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including "the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue." Id. at 1359.
A written description of a chemical genus "requires a precise definition, such as by
structure, formula, [or] chemical name" of the claimed subject matter sufficient to distinguish it
from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed.
Cir. 1997). The Federal Circuit reflected on Eli Lily in Ariad while explaining how to sufficiently
describe of a genus of compounds:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F .3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented age nus and not just a species.
A "representative number of species" must typify the entire claimed genus and account
for variation between the species of the genus.
[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated. Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
Claim 1, 15, and 22-25 recite a compound of formula (I), wherein substituents are selected from an extensive set of chemical groups. The size of this genus of claimed compounds may be roughly determined by cumulatively multiplying the number of possibilities, n, for each possible substitution around the rings, specifically at the Rx, Rx’, RY, RY’, CyB, CyA, L, CyC, RD, and RC:
(#permutations at Rx) x (#permutations at Rx’) x (#permutations at RY) x (#permutations at RY’) x (#permutations at CyB) x (#permutations at CyA) x (#permutations at L) x (#permutations at CyC) x (#permutations at RD) x (#permutations at RC) = Total compounds
Taking the CyA as an example, the number of possible substitutions is not limited, thus, a conservative estimate of the number of possible substitutions would be in the thousands
(103) at a minimum. By inserting the optionally substituted groups into the equation, these estimates yield results in the billions (1012) of compounds making up the claimed genus.
By contrast to billions of claimed compounds, the specification provides very few species
of compounds typifying the claimed genus. For example, the specification (page 65-271) depicts about 108 species with very little variation at RY, RX, CyA and CyB i.e., there is limited substitution on CyA and CyB only discloses species with methyl, cyclopropyl ring, chlorine, and methylamino group, as an example. Furthermore, the specification only disclosed CyA as an 8- or 10 membered bicyclic heteroarylene containing nitrogen heteroatoms, with a limited set of structures in which a sulfonyl group is incorporated into the ring in combination with one or two nitrogens. No bicyclic heterocylces containing oxygen as a ring heteroatom, nor any structure containing mixed O/N/S heteroatom combination, are described, as an example of lack representation of the breadth of the claimed genus. Similarly, these deficiencies are also present in claims 2 to 4, 8, 13-16, 18, 20, 22-24, which recite a broad range of RA, RB, RA, Lc and Rc substituents without providing representative species supporting the full scope of the claimed structural diversity. Therefore, the 108 species of as presented in the specification offered to support the genus of billions of compounds account for very little variation as compared to the claimed genus. These 109 supporting species, which lacks variation among the substituents, cannot possibly account for the variability found across a genus that encompasses billions of compounds.
Chemistry is generally considered to be unpredictable and/or have unpredictable factors.
See, e.g.,ln re Carleton, 599 F.2d 1021, 202 USPQ 165,170 (CCPA 1979) ("Although there is a
vast amount of knowledge about general relationships in the chemical arts, chemistry is still
largely empirical, and there is often great difficulty in predicting precisely how a given compound will behave."). The pharmaceutical arts, that is the use of a chemical compound to affect a desired physiological activity, is generally considered to be unpredictable and/or have
unpredictable factors. See, e.g., In re Fisher, 427 F.2d 833, 839 (CCPA 1970) ("In cases
involving unpredictable factors, such as most chemical reactions and physiological activity, the
scope of enablement obviously varies inversely with the degree of unpredictability of the factors
involved (emphasis added); In re Bowden, 183 F.2d 115, 86 USPQ 419, 423 ("chemical reactions frequently are unpredictable").
Considering the unpredictability found in organic synthesis, exchanging even one
substituent for another cannot be considered a foregone conclusion. Accordingly, when a claim
presents a genus with substantial variation as that currently presented by claim 1, the disclosure must adequately reflect such variation with a representative number of species.
The lack of any disclosure of examples may be considered in determining whether a claimed invention was adequately described. Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d
1353 (Fed. Cir. 2011).
As is the case here, very few examples do not provide a "representative number of
species" for an unpredictable art such as a chemistry. See, e.g., Ariad, 598 F.3d at 1354-55
(claiming that the inventor has an obligation to disclose examples when the art is unpredictable).
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying
characteristics demonstrating that Applicant was in possession of the entirety of the genus now
claimed, i.e., additional complete or partial structures, other physical and/or chemical properties,
functional characteristics coupled with a known or disclosed correlation between function and
structure, or some combination thereof demonstrating possession of the entirety of the claimed
genus.
Claim Rejections - 35 USC § 112
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 27 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 27 recites “The compound of claim 1, wherein the compound is selected from Table A.” Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609.
(See MPEP 2173.05(s)).
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.
Claims 1-5, 8, and 10 are rejected under 35 U.S.C. 102(a)(l) as being anticipated by PubChem CID 10156439 (2006-10-25).
Regarding claim 1-2, 8, 10, 13-14, 22, PubChem CID 10156439 teaches compound N-(1H-indazol-3-yl)-2-(2-phenylcyclopropyl) quinazolin-4-amine, wherein CyB is phenyl and the substituent RB is 0; Rx, Rx’, RY and RY’ are hydrogen; CyA is quinazoline and the substituent RA is 0; L is NH; and Cyc is benzimidazole and the substituent LC-RC is 0.
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Therefore, claims 1-2, 8, 10, 13-14, and 22 are anticipated.
Subject Matter Free of the Art of Record
The subject matter of claim 3-7, 9, 11-12, 15-21, 23-28 is free of the art of record. The closest prior art is PubChem CID 10156439. While PubChem CID 10156439 teaches compound N-(1H-indazol-3-yl)-2-(2-phenylcyclopropyl) quinazolin-4-amine, however there is no motivation for an ordinary skill in the art to modify the teaching of PubChem CID 10156439 to arrive at the claimed compound. These claims are not allowable until the 112 rejection is resolved.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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