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
This application claims priority to US Provisional Application No. 63/286,749, filed December 7, 2021.
Election/Restrictions
Applicant’s election of Group I with the addition of
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as the elected compound species in the reply filed on 08/07/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 6, 7, 16, 19, and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/07/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/26/2024 has been considered by the examiner.
Status of Claims
Claims 1-3, 5-8, 11-12, 14-16, 18-19, 21-26 are pending. Claims 6, 7, 16, 19, and 24-26 are withdrawn. Claims 1-3, 5, 8, 11-12, 14-15, 18, and 21-23 are examined in accordance to the elected species.
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 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.
Claims 1-3, 5, 8, 11-12, 14-15, 18, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Amberg et al. (US2017/0174672 A1); hereinafter “Amberg”) in view of Lange et al. (WO2012/020133 A1; hereinafter “Lange”).
Amberg relates to fused (hetero)cyclic compounds having affinity for sphingosine-1-phosphate (SIP) receptors and their use in treating diseases and conditions involving S1P receptors. See ¶[0001]. Amberg also teaches a pharmaceutical composition comprising a compound according to the invention or a pharmaceutically acceptable salt, Solvate, tautomer, Stereoisomer or N-oxide thereof, and at least one pharmaceutically acceptable carrier, diluent and/or excipient. See ¶[0658]. Amberg particularly concerns modulators of the S1P5 receptor, especially agonists, and explains that S1P5 is primarily expressed in the CNS. See ¶¶[0003]-[0004], p. 1. Amberg further teaches the usefulness of S1P5 modulation in cognitive and neurodegenerative disorders and discusses, inter alia, Alzheimer’s disease and multiple sclerosis. See ¶¶[0004]-[0008]. Pp. 1-2. Of particular relevance, Amberg Compound 2 is:
1-(6-((2-chloro-6-ethylbenzyl) oxy)-1,2,3,4-tetrahydronaphthalen-2-yl) azetidine-3-carboxylic acid. See ¶¶[0720]-0722], p.30, particularly p. 30, lines corresponding to the heading for Compound and its preparation. Amberg teaches that Compound 2 is prepared according to the procedure for Compound 1, except that 6-hydroxy-3,4-dihydronaphthalen-2(1H)-one is employed in place of 7-hydroxychroman-3-one and 2-(bromomethyl)-1-chloro-3-ethylbenzen is employed in place of 2-(bromomethyl)-1-chloro-3-ethylbenzene is employed in place of 2-(bromoethyl)-1,3-dichlorobenzen. See ¶[0721], p. 30. Amberg additionally provides analytical characterization of Compound ¶[0722].
Accordingly, Compound 2 expressly possesses:
an azetidine ring;
a carboxylic acid at the 3-position of the azetidine;
attachment of the azetidine nitrogen to the fused bicyclic core;
a tetralin (1,2,3,4-tetrahydronaphthalene) fused bicyclic core;
a terminal benzyl phenyl ring bearing both chloro and alkyl substitution.
Thus, Amberg Compound 2 differs from the presently elected species
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principally in that (1) Amberg employs a tetralin core whereas the elected species employs a tetralin core whereas the elected species employs the corresponding one-carbon-smaller indane core and (2) Amberg Compound 2 bears ethyl at the pertinent alkyl-substituted position of the benzyl phenyl ring whereas the elected species bears methyl.
This structural relationship is especially significant because these differences do not
require reconstruction of the azetidine-carboxylic-acid pharmacophore or the benzyloxy linkage from unrelated teachings.
Amberg also expressly demonstrates that the tetralin/azetidine-3-carboxylic-acid
structure is not an isolated disclosure. For example, Compound 4 is 1-(6-((2,6-dichlorobenzyl) oxy)-1-1,2,3,4-tetrahydronaphthalen-2-yl)azetidine-3-carboxylic acid. See ¶¶ [0726]-[0730], p. 31. Amberg describes preparation of the tetralin/azetidine intermediates and subsequent benzylation and conversion to the carboxylic acid. Amberg therefore expressly demonstrates variation of the terminal benzyl substituents while maintaining the tetralin-azetidine-3-carboxylic-acid architecture.
Amberg additionally teaches that the pertinent phenyl group may be optionally
substituted by one or more substituents independently selected from, inter alia, halogen and C1-4alkyl. See ¶¶[0221]-[0229], p. 10, particularly ¶¶[0223]-[0229]. Amberg repeats the same preferred phenyl substitution teaching at ¶¶[0237]-[0245], p. 11. Thus, the disclosure expressly encompasses both chloro as the halogen and methyl as a C1-4 alkyl substituent.
Amberg’s Compound 2 narrower supplies concrete exemplification of the immediately
neighboring ethyl species. Accordingly, replacement of ethyl by methyl does not require selection of an unrelated functional group but instead represents selection of an expressly disclosed member of Amber’s lower-alkyl genus at a position Amberg demonstrates may bear lower alkyl.
Amberg does not expressly disclose Compound 2 with indane core in place of its tetralin
core.
Lange expressly relates to “tetralin and indane derivatives” and pharmaceutical
compositions containing such compounds. See Title and p. 1. Lange’s disclosure therefore provides evidence that skilled artisan recognized tetralin and indane as closely related fused carboxylic scaffolds suitable for use as alternative medicinal-chemistry framework. Structurally, conversion of Amberg’s tetralin ring to the presently elected indane ring corresponds to removal of a methylene unit from the saturated portion of the fused bicyclic ring system. Tetralin and indane therefore stand in the conventional homologous relationship relevant to medicinal-chemistry structural modification.
MEPE §2144.09 explains that homologs differing regularly by addition or removal of a
common group, such as -CH2-, generally possess sufficiently close structural similarity to give rise to an expectation of similar properties, although the homologous relationship must be considered together with all of the relevant evidence.
The Federal Circuit’s predecessor court similarly explained that obviousness based upon
close chemical structural and function considers whether the ordinary artisan would have been motivated to make the structurally related compound with an expectation that structurally similar compounds would possess similar properties. In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). MEPE §2144.09.
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to prepare the indane homolog of Amberg Compound 2. Amberg already identifies Compound 2 as a member of its S1P-modulating compound series and expressly provides the complete substituted-benzyloxy/tetralin/azetidine-3-carboxylic-acid architecture. Amberg ¶¶[0720]-[0722], p. 30. Lange independently establishes that tetralin and indane were recognized as closely related fused carboxylic medicinal-chemistry scaffolds.
A person of ordinary skill seeking additional analogs of Amberg Compound 2 would
therefore, have had reason to investigate the corresponding one-carbon-smaller indane homolog, because Lange teaches the indane and tetralin fused-ring systems together as closely related medicinal-chemical scaffolds, while the modification preserves the remaining structural architecture of Amberg Compound 2.
The proposed modification does not depend upon hindsight selection of several
unrelated fragments from disparate references. Rather, Amberg supplies substantially the complete molecule and Lange supplies evidence supporting the specific homologous modification of the fused carbocyclic ring.
It further would have been obvious to employ methyl in place of the ethyl of Amberg
Compound 2, because Amberg expressly teaches C1-4 alkyl substitution of the pertinent phenyl group, which includes both methyl and ethyl. See ¶¶ [0223]-[0229], p. 10 and ¶¶[0239]-0245], p11. Compound 2 provides an actual chloro/ethyl embodiment, while Amberg expressly identifies lower alkyl generally as suitable at such aromatic substituent position. Thus, methyl represents an expressly contemplated lower homolog of the exemplified ethyl substituent, rather than a substituent selected only after knowledge of Applicant’s disclosure.
One of ordinary skill in the art would have had reasonable expectation that the resulting
compound would retain the relevant S1P-modulating properties of Amberg’s compounds. Amberg expressly identifies its compounds as S1P receptor modulators and particularly concern S1P5 agonists. See ¶¶[0001], [0003]-[0008], pp. 1-2. Moreover, the proposed modification preserves the azetidine-3-carboxylic acid, N-to-fused-ring connectivity, benzyloxy linkage, substituted terminal phenyl group, and fused aromatic carbocyclic framework of Compound 2.
The modifications are limited to:
contraction of the saturated ring of tetralin by one methylene to provide its closely related indane homolog, which Lange establishes as a recognized related fused-ring scaffold; and
replacement of ethyl by methyl both of which fall within Amberg’s expressly disclosed lower-alkyl substituent class.
Close structural similarity coupled with similar disclosed utility supports an expectation that closely related compounds will possess similar properties. MPEP §2144.09; in re Payne, 606, F.2d at 313. Absolute predictability is not required; the standard is a reasonable expectation of success. MPEP §2144.09.
Accordingly, one of ordinary skill would reasonably have expected the indane/methyl
homolog to retain useful S1P receptor-modulating activity.
Conclusion
Claims 1-3, 5, 8, 11-12, 14-15, 18, and 21-23 are not allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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