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 without traverse of Group II (drawn to a polycyclic amide derivative represented by formula (II) or formula (III)), in the reply filed on 01/06/2026 is acknowledged.
Claims 1-10 are pending of which claims 1, 3-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected INVENTION, there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 2 has been examined on the merits.
Applicant elects a compound recited in claim 2, having the following structure:
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Wherein Rc is C(O)NH2, R1 is hydrogen, R2 is 5-7 membered cycloalkyl, substituted with Ra which is NHC(O)Rb, and Rb is C1-3 alkyl.
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 and
the prior art has been applied to the generic claims, as discussed below. MPEP §
803.02(III)(C)(2).
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.
Claim 2 is 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 Lil/yin Ariadwhile 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 2 recites a polycyclic amide derivative represented by formula (II) or (III) 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 R1, R2, Rc, Ra, Rb, Ra1, and Rd:
(#permutations at R1) x (#permutations at R2) x (#permutations at Rc) x (#permutations at Ra (#permutations at Rb) x (#permutations at Ra1) x (#permutations at Rd) = Total compounds
Taking the R1 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 5-16) depicts about 59 species with very little variation at R2, and Rc, i.e., Rc only discloses species with CN, H, C(O)N(CH3)2 and C(O)NH2. The 59 species of as presented in the specification and claim 2offered to support the genus of billions of compounds account for very little variation as compared to the claimed genus. These 59 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 2, 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 § 103
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 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office
action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3 is rejected under 35 U.S.C. 103 as being unpatentable over Pike et al.,
in view of Belal et al., Bioorg Med Chem. 2014 Jan 1;22(1):46-53.
Pike (abstract) teaches “pyridine or pyrimidine derivatives of Formula (I) which inhibit CDK9 and may be useful for the treatment of hyperproliferative diseases,” such as cancer. Pike (page 185) teaches a compound of Example 43, wherein R1 is Cl; R2 is 6-membered cycloalkyl
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or diaza-pyrrolizine, substituted with Ra which is NHC(O)Rb, and Rb is C1-3 alkyl or methyl. Pike, however, does not explicitly teach mono-nitrogen pyrrolizine and Rc is hydrogen.
Nonetheless, Belal (abstract) teaches “pyrrolizine derivatives constitute a class of heterocyclic compounds which can serve as promising scaffolds for anticancer drugs.” Belal (abstract; page 46-47) discloses that pyrrolizine scaffolds possess broad antitumor activity. Given the share anticancer activity and the close structural similarity between diaza-pyrrolizine as disclosed by Pike and pyrrolizine ring, therefore, a person of ordinary skill in the art (POSITA)
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would consider modifying Pike’s disclosure by removing one nitrogen from the bicyclic heteroaromatic core to obtain mono-nitrogen pyrrolizine derivatives, as this would allow expansion of the pyrrolizine-derivatives library in the search for potent anticancer agents; and to arrive at the claimed invention; wherein Rc is hydrogen.
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