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 .
Claim Status
Claims 1, 2, 4, 6, 9, 10, 12, 13, 24, 26, 29, 30, 32, 45, 46, 49-51, 54, 59, 75-77, and 80 are pending.
Claims 1-2, 6, 12-13, 29-30, 32, 46, 49-50, 54, 59, and 75-76 are examined herein.
Claims 4, 9, 10, 24, 26, 45, 51, 77 and 80 are withdrawn (see restriction/election below).
Priority
This application is filed 5/21/2024, and claims the benefit of domestic priority as below:
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Information Disclosure Statements
One IDS(s) received on 09/04/2024 has been considered unless marked with a strikethrough.
Election/Restrictions
Applicants elect Group I (Claims 1, 2, 4, 6, 9, 10, 12, 13, 24, 26, 29, 30, 32, 45, 46, 49-51, 54, 59, 75, and 76), is drawn to a compound or a pharmaceutical acceptable salt thereof, and pharmaceutical compositions comprising such compounds or salts, without traverse in the reply field on 08/14/2026 is acknowledged. Group II (Claims 77, and 80) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use, there being no allowable generic or linking claim.
Applicant’s election the compound 102,
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in claim 75, in the reply field on 08/14/2026 is acknowledged. Claims 1-2, 6, 12-13, 29-30, 32, 46, 49-50, 54, 59, and 75-76 read on the elected species and will be examined on their merits. Claims 4, 9, 10, 24, 26, 45, and 51 that do not read on the elected species are withdrawn from further consideration.
If the elected species is not identified in the prior art, the elected species would be allowable if an independent claim was drafted with that species alone. (see MPEP 802.03)
The elected species was not identified in prior arts. Further, the Examiner expanded the
search for alternative species. No anticipatory art was found of the elected/ alternative species, and no motivation was found to make an obvious-type 103 rejection.
As set forth below, claims 1-2, 6, 12-13, 29-30, 32, 46, 49-50, 54, 59, and 75-76 in Group I rejected under 35 USC 112(a) or objected to as an internal disclosure-based rejection focused on the contents of the patent application's own specification rather than external prior art references.
Claim Objections
Claims 13, 59, and 75 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112, Written Description
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 1-2, 6, 12, 29-30, 32, 46, 49-50, 54, and 76 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by applicants. (see MPEP 2163.02)
An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Further, the MPEP states that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. (see MPEP 2161.01)
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171, the court stated as follows:
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 [25 USPQ2d 1601] (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 a genus and not just a species.
With respect to claim 1, the claim recites compounds of Formula (I) wherein “Ring A is phenyl, or 5- to 6-membered heteroaryl comprising one, two, or three heteroatoms independently selected from the group consisting of 0, N, and S”. Thus, claim 1 encompasses a broad of 5- to 6-membered aryl and heteroaryl rings having different numbers, identities, and arrangements of nitrogen, oxygen, and sulfur atoms.
The specification provides working examples containing several Ring A classes, including phenyl, pyridyl, pyrimidinyl, and pyrazolyl groups. Thus, the issue is not that the disclosure is limited to a single heteroaryl class. Rather, the claimed genus extends to additional heteroatom compositions and arrangements, including sulfur or oxygen containing Ring A systems, that are not comparably represented or functionally characterized in the specification.
The specification itself shows that Ring A structure can materially affect the biological activity relied upon in the application. For example, compounds 226 and 230 contain the same 2-thia-7-azaspiro[3.5]nonane scaffold and closely related aryl ether substituents, but compound 226 contains a 4-(trifluoromethyl)phenyl Ring A, whereas compound 230 contains a 6-(trifluoromethyl)pyridine-3-yl Ring A (paragraph [131]). Compound 226 exhibits an hEBP-DHCRE7 Ki of 0.00929 uM, mZymoGCMS EC50 of 0.00088 uM, and an mOPC EC50 of 0.0022 uM, whereas compound 230 exhibits corresponding values of 0.749 uM, 0.011 uM, and 0.022 uM (paragraph [707]). Thus, even introduction of a single ring nitrogen in an otherwise closely related Ring A system is associated with a substantial change in EBP related and cellular activity. Similarly, compounds 152 and 153 provide comparison between pyridyl and phenyl ring A system and further show that changes in Ring A identity can alter hEBP-DHCRE7, mZymoGCMS, and mOPC differentiation activity (paragraph [131], and [707]). These results support that different Ring A heteroatom compositions cannot be presumed to be functionally interchangeable. Accordingly, the specification does not provide representative sulfur and/or oxygen containing Ring A species or another structure function relationship sufficient to show possession of the sulfur/oxygen containing portion of the genus encompassed by claim 1.
Claim 12 is narrower than claim 1 but does not cure the deficiency. Claim 12 limits Ring A to the six-membered Formula (Ib) genus, while continuing to permit nitrogen and sulfur containing ring systems. The more specific Formula (Ib)embodiments principally identity carbon and nitrogen containing arrangements, including mono and di nitrogen containing six membered rings, but do not provide a corresponding representative disclosure of sulfur containing species. Accordingly, claim 12 continues to encompass a structurally distinct sulfur containing subclass that is not adequately represented in the specification as discussed above.
Allimuthu et al. (Cell Chem. Biol., 26(4), 593-599, pub’d 02/14/2019, made of record in the IDS) teaches that small molecules that promote oligodendrocyte formation have been identified in ‘drug repurposing’ screens to nominate candidate therapeutics for diseases, and evaluation of analogs led to identification of CW3388, a potent EBP-inhibiting enhancer of oligodendrocyte formation poised for further optimization (abstract). The results of Allimuthu’s study support that EBP inhibition and oligodendrocyte promoting activity can vary among closely related compounds (results section). Long et al. (Nat. Commun., 10(1), 2452, pub’d 06/05/2019) shows crystal structures of human EBP bound to pharmacologically active ligands (abstract). Long identifies a defined ligand binding cavity and teaches that specific ligand protein interactions are involved in EBP recognition. Mutagenesis of particular binding site residues decreased ligand binding capacity and, for certain residues, abolished isomerase activity (abstract, results section with Fig. 2-6). Thus, Long supports that EBP associated activity depends upon molecular recognition of specific structural features of a ligand.
Allimuthu and Long are not relied upon to establish that any particular sulfur/oxygen containing Ring A compound is inactive. Rather, they support the structural sensitivity demonstrated by the biological data in the instant specification and show that equivalent EBP associated function cannot be inferred from a broad heteroaryl class.
For a genus claim under MPEP 2163 (35 U.S.C. 112(a)), possession of the claimed invention can be demonstrated either by disclosing a representative number of species or by disclosing relevant, identifying characteristics such as structural features, formulas, or physical/chemical properties common to the members of the genus. Here, the disclosed species and functional data do not reasonably convey possession of the full scope of Ring A encompassed by claims 1 and 12.
Claims 2, 6, 29-30, 32, 46, 49-50, 54, and 76 narrow selected structural variables or compound’s composition of claim 1 and/or claims 12 but continue to encompass the broad Ring A definition discussed above. Those additional limitations do not cure the written description deficiency.
As set forth in the en banc decision in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010), to satisfy the written description requirement, the 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 at the time of filing. Specifically, the specification must describe the claimed invention in a manner understandable to a person of ordinary skill in the art in a way that shows that the inventor actually invented the claimed invention at the time of filing. Id.; Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. (see MPEP 2161.01).
Accordingly, in view of the broad scope of Ring A, the lack of a representative number of species encompassing the substantially different classes of Ring A, the biological data of the instant specification, and the unpredictability of functionality suggested by Allimuthu and Long, the specification fails to reasonably convey to a person skilled in the art that the inventors were in possession of the full scope of the claimed combination therapy at the time of filing.
Conclusion
Claims 1-2, 6, 12, 29-30, 32, 46, 49-50, 54, and 76 are rejected.
Claims 13, 59, and 75 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
