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 .
DETAILED ACTION
Claims 1-13 and 15-24 are pending in the instant application.
Election/Restrictions
Applicant’s election with traverse of Group I,
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and the election of the species of the claimed pharmaceutical composition comprising (3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-isoxazole-3-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide (the COMPOUND) and the S1P1 receptor modulator Fingolimod,
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in the reply filed on February 4, 2026 is acknowledged.
The traversal is on the ground(s) that Chen et al. primarily disclose compounds or their pharmaceutically acceptable salts that are effective in inhibiting the binding or function of chemokines to the CCR9 chemokine receptor {paragraphs [0004] and [0011]} whereas the compounds of the present disclosure have been shown to modulate CCR(9).
In response, Chen et al. {paragraph [0119] on page 14} teach that one of the embodiments of his invention is that diseases or conditions may be treated with modulators and agonists of CCR(9), which diseases include cancers, cardiovascular diseases, etc. Applicant has stated that the compounds of the present disclosure have also been shown to modulate CCR(9) too. Therefore, Applicant’s argument is not persuasive.
Applicant argues that Chen et al. disclose combinations of his CCR(9) modulators with one or more other therapeutic agents and thus, Chen et al. do not disclose a combination of a CXCR7 modulator (like “the COMPOUND” of the instant invention) with a S1P1 modulator in absence of a CCR(9) modulator nor does Chen et al. disclose pharmacological effect of such a combination.
In response, instant independent claim 1 states “A pharmaceutical composition comprising”. The transitional term “comprising” is open-ended and does not exclude additional ingredients which can be present in the claimed pharmaceutical composition. See MPEP §2111.03(I).
As stated in the lack of unity, Chen et al. {paragraphs [0126]-[0127] on pages 14-15} teach pharmaceutical compositions comprising modulators of CXCR7 in combination with fingolimod, etc. Further, Chen et al. {paragraph [0111] on page 13} teach that “The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.” Therefore, Chen et al. do teach a pharmacological effect of the combination of therapeutic agents. For all the reasons given above, Applicant’s arguments are not persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 4-13, 15 and newly added claims 17-24 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. Applicant timely traversed the restriction (election) requirement in the reply filed on
February 4, 2026.
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims will be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statements filed on May 2, 2022 (2) and January 6, 2026. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 24, line 32, of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Aissaoui et al. {WO 2018/019929 A1} in combination with the teachings in each of Chen et al. {US 2017/0204087} and Legangneux {WO 2010/072703 A1}.
Determination of the scope and content of the prior art (MPEP §2141.01)
Applicant claims a pharmaceutical composition comprising:
(3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-isoxazole-3-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide (the Compound) or a pharmaceutically acceptable salt thereof,
in combination with a sphingosine-1-phosphate receptor 1 (S1P1) receptor modulator (such as fingolimod) or a pharmaceutically acceptable salt thereof, and
as well as at least one pharmaceutically acceptable excipient.
Aissaoui et al. disclose the COMPOUND of the
instant invention (page 206 - Compound 4.032 and claim
12, page 262, lines 3-4) and that his compounds are
modulators of the CXCL11/CXCL12 receptor CXCR7 (page 1,
lines 1-19). Aissaoui et al. teach that his compounds
are useful for treating disorders relating to the CXCR7
receptor such as various cancers, inflammatory diseases (i.e., asthma), autoimmune disorders (i.e., multiple sclerosis), transplant rejection, etc. (page 104). Aissaoui et al. teach pharmaceutical compositions (page 7, lines 19-20) comprising the COMPOUND (page 206 - Compound 4.032 and claim 12, page 262, lines 3-4), a pharmaceutically acceptable excipient (claim 13, page 268) and additional therapeutic agents.
Ascertainment of the difference between the prior art and the claimed invention (MPEP §2141.02)
The difference between the pharmaceutical composition of Aissaoui et al. and the pharmaceutical composition instantly claimed is that Aissaoui et al. do not teach specifically an S1P1 receptor modulator (such as fingolimod) as the “additional therapeutic agent” in his pharmaceutical composition.
Finding of prima facie obviousness--rational and motivation
(MPEP §2142-2143)
However, Chen et al. teach pharmaceutical compositions comprising modulators of CXCR7 in combination with fingolimod, ozanimod, etc. {paragraphs [0126]-[0127] on pages 14-15}. Chen et al. {paragraph [0119] on page 14} teach that one of the embodiments of his invention is that diseases or conditions may be treated with modulators and agonists of CCR(9), which diseases include cancers, cardiovascular diseases, etc. The pharmaceutical compositions of Chen et al. can be administered for the treatment of autoimmune diseases, asthma, leukemia, etc. {paragraph [0028] on page 2}. Further, Chen et al. {paragraph [0111] on page 13} teach that “The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.” Therefore, Chen et al. teach a pharmacological effect of the combination of therapeutic agents.
Legangneux teaches standard daily dosage regimen for S1P receptor modulator or agonist (pages 2-3). Legangneux teaches that a lower than the standard daily therapeutic dosage is administered for treating a patient in need of a S1P receptor modulator or agonist (such as treating an autoimmune condition like multiple sclerosis).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the instant claimed invention, to prepare pharmaceutical compositions as taught by the prior art. A person of ordinary skill in the art would have been motivated to prepare pharmaceutical compositions taught by Aissaoui et al. in combination with the teachings in each of Chen et al. and Legangneux to arrive at the instant claimed pharmaceutical composition with the expectation of obtaining additional beneficial pharmaceutical compositions which could be administered in the treatment of various diseases or conditions such as cancer, cancers, inflammatory diseases, autoimmune disorders (i.e., multiple sclerosis), etc. The instant claimed invention would have been suggested to one skilled in the art and therefore, the instant claimed invention would have been obvious to one skilled in the art.
The elected species of the claimed pharmaceutical composition comprising (3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-isoxazole-3-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide (the COMPOUND) and the S1P1 receptor modulator Fingolimod, is not allowable over the prior art of record. See the above rejection under 35 USC 103.
Reminder to Applicant
As a reminder, Applicant should specifically point out the support in the original disclosure {i.e., page number(s) and line number(s)} for any new claims or amended claims and for any amendments made to the disclosure. Making generic statements such as “all amendments are fully supported in the originally filed disclosure or the originally filed claims” without specifying page numbers and originally filed claim numbers are insufficient. See MPEP §714.02 and MPEP §2163.06(I).
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to:
Laura L. Stockton
(571) 272-0710.
The examiner can normally be reached on Monday-Friday from 8:30 am to 6 pm, Eastern Standard Time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s acting supervisor,
James Alstrum-Acevedo can be reached on 571/272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LAURA L STOCKTON/ Primary Examiner, Art Unit 1626 Work Group 1620
Technology Center 1600
April 13, 2026
Book XXVII, page 89
Prosecution Insights