1867DETAILED 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, 4, 8, 9, 11, 12, 15, 18, 20, 29, 31, 32, 35, 40, 42, 47-50, and 53 are pending.
Claims 1, 4, 8, 9, 11, 12, 15, 18, 20, 29, 31, 32, 35, 40, 42, 47-49 are examined herein.
Claims 50 and 53 are withdrawn (see restriction/election below).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 09/05/2024 has been considered unless marked with a strikethrough.
Election/Restrictions
Applicants elect Group I (Claims 1, 4, 8-9, 11-12, 15, 18, 20, 29, 31-32, 35, 40, 42, and 47-49), 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 08/19/2026 is acknowledged. Group II (Claims 50, and 53) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use, there being no allowable generic or linking claim.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 48,
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in claim 3 in the reply field on 08/19/2026 is acknowledged. Claims 1, 4, 8-9, 11-12, 15, 18, 20, 29, 31-32, 35, 40, 42, and 47-49 read on the elected species and will be examined on their merits.
If the elected species is not identified in the prior arts, 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, 4, 8-9, 11-12, 15, 18, 20, 29, 31-32, 35, 40, 42, 47, and 49 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.
Abstract
The abstract of the disclosure is objected to because the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. Currently, the abstract has 45 words.
The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. Examiner requests to bring satisfied form the abstract requirement.
Correction is required. See MPEP § 608.01(b).
Claim Objections
Claims 18, 20, 29, 31, and 48 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, 4, 8, 9, 11, 12, 15, 32, 35, 40, 42, 47 and 49 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 a 5-membered heteroaryl comprising one, two, or three heteroatoms independently selected from the group consisting of O, N, and S”. Thus, claim 1 encompasses a broad of five membered heteroaryl rings having different numbers, identities, and arrangements of nitrogen, oxygen, and sulfur atoms.
However, although the specification identifies a general description of “heteroaryl” extending beyond the scope of Ring A has been provide (paragraph [51]), the specification further identifies limited Ring A embodiments. In particular, the specification states that, “Ring A comprises one, two, or three N.”, and further identifies Ring A as “pyrazolyl, triazolyl, and imidazolyl” (paragraph [90]). Therefore, the specifically identified embodiments emphasize nitrogen containing five membered heteroaryl systems.
For a genus claim, written description may be established by disclosure of a representative number of species or by disclosure or relevant identifying characteristics sufficient to show possession of the genus. (see MPEP 2163) This written description issue is whether the disclosure reasonably conveys possession of the broader claimed genus, including materially different O and S containing Ring A structures, as members of the genus associated with the biological function described in the specification.
The specification identifies the functions for the compounds. It describes the compounds as myelin promoting compounds and explains that compounds of Formula (I) can modulate cholesterol biosynthesis (paragraph [166]). Specifically, the specification states that compounds of Formula (I) can inhibit emopamil binding protein (EBP) and can inhibit the EBP mediated conversion of zymostenol to lathosterol (paragraph [17]-[19]). The specification further explains that inhibition of this pathway can results in accumulation of Δ8,9-unsaturated sterol intermediates in oligodendrocyte differentiation, survival, proliferation, and/or maturation and thereby promote myelination (paragraph [20]). Accordingly, the specification links the claimed chemical structures to a particular biological function involving cholesterol biosynthesis modulation, EBP associated activity, and promotion of oligodendrocyte differentiation and myelination.
However, the specification merely presents biological functional properties for pyrazolyl,
triazolyl, imidazolyl, and related nitrogen-containing embodiments; it fails to demonstrate possession of the entire class of substantially different 5-membered heteroaryl rings encompassed by Ring A as compounds sharing the disclosed biological function. In particular, the disclosure does not establish that the inventors possessed O and S containing Ring A classes as part of the same functional genus represented by the specifically identified nitrogen containing Ring A systems.
This distinction is material because five membered heteroaryl rings having different heteroatom identities and arrangements are not necessarily functionally interchangeable. Perrone et al. (ChemMedChem., 7(4), 629-41, pub’d 01/25/2012) studies related compounds in which the five membered heterocyclic core was varied, and reports that replacement of an isoxazole core with an isothiazole or pyrazole core resulted in a drastic decrease in COX-1 inhibitory activity (results and discussion section). Thus, Perrone presents experimental evidence demonstrating that, even within a structurally similar chemical class, altering the type and arrangement of heteroatoms in a five-membered heterocycle can lead to substantial differences in biological activity. Perrone is not cited to demonstrate the activity or inactivity of the specific Ring A compounds currently claimed. Rather, Perrone supports the position that structurally distinct five-membered heteroaryl systems cannot simply be assumed to behave alike merely because they belong to the same functional class. This point is particularly relevant to the instant specification, given that EBP is specifically identified as a biological target associated with the compounds of the invention. Moreover, 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.
In view of Perrone and Long, the specification does not disclose a reasonable structure function correlation sufficient to show possession of the full scope extending from the specifically identified nitrogen containing Ring A systems to all O, N, and S containing five membered heteroaryl ring encompassed by claim 1. Furthermore, the specification does not disclose a representative number of species encompassing the substantially different classes of Ring A included in the claims. Therefore, the mere disclosure of pyrazolyl, triazolyl, imidazolyl, and related nitrogen-containing embodiments cannot be considered to reasonably convey possession of the entire Ring A genus, absent the presentation of additional distinguishing characteristics or established structure-function relationships.
The reason for this rejection is not based on a lack of working examples for every claimed species; the written description requirement does not mandate that every species within a genus be individually exemplified. Rather, the issue is that the disclosed species fail to adequately represent the structural and functional diversity of the claimed Ring A genus, and the specification does not provide sufficient identifying characteristics to demonstrate that the inventors possessed the broader O, N, and S containing genus as of the effective filing date.
Claims 4, 8, 9, 11, 12, 15, 32, 35, 40, 42, 47 and 49 narrow selected structural variables 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, and the unpredictability of functionality suggested by Perrone 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.
Art of Record but not Applied
WO 2015/091889 A1 (pub’d 2015091889, made or record in the IDS) teaches relevant structural prior art because it discloses pyrazole containing compounds bearing spiro-substituted bicyclo[3.1.0]hexane moieties framework. However, it does not disclose the specific overall structural combination required by the instant claims, including the claimed SO2- containing spiro moiety and the particular E1-E5 arrangement of Formula (Ic). In addition, the biological teaching of ‘889 patent is also materially different. ‘889 patent is directed to compounds develop as inhibitors of dual leucine zipper kinase (DLK/MAP3K12). By contrast, the compounds of the instant claims are directed to modulation of cholesterol biosynthesis and promotion of remyelination. Accordingly, 889 patent lacks enough of the same embodiments to qualify as 102 and 103 prior art.
Conclusion
Claims 1, 4, 8, 9, 11, 12, 15, 32, 35, 40, 42, 47 and 49 are rejected.
Claims 18, 20, 29, 31, and 48 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
