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 .
Status of the Claims
Claims 1-6 and 8-11 are pending in the instant application and subject to examination herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/EP2023/055672, filed on 03/07/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/06/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5-6 and 8-11 are anticipated by An.
Claims 1, 5-6 and 8-11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by An (WO 2012/100436 A1)1.
Claim 1 is drawn to a genus of amidocyclopropyl compounds, designated as formula (I), including a 5-membered heteroaryl ring, a 6-membered aryl or heteroaryl ring, and additional substituents and limitations as shown in the table below. An discloses a genus of arylamido and arylsulfonamido compounds, including multiple compounds that anticipate the instant formula (I), for example An’s compound 102 shown in the table below:
Claim Number(s) of Instant Application
Instant Application
An
1
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362
244
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Greyscale
wherein:
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348
278
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Greyscale
Compound 10
Thus, claim 1 is anticipated by the disclosure of An.
Claim 5 further limits claim 1 to a pharmaceutical composition comprising the compound according to claim 1, in admixture with one or more pharmaceutically acceptable carriers or excipients. Claim 6 further limits claim 5 to wherein the pharmaceutical composition is formulated for administration by inhalation.
An discloses a pharmaceutical composition comprising a therapeutically effective amount of a compound disclosed therein or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable inactive ingredient such as a carrier or diluent, and further discloses that such composition may be manufactured in a conventional manner by mixing, granulating or coating method for various routes of administration, including inhalation (page 5, central paragraph).
Thus, claims 5-6 are anticipated by the disclosure of An.
Claim 8 further limits claim 1 to a method for treating a disease, disorder or condition associated with dysregulation of lysophosphatidic acid receptor 1 (LPA1), comprising administering the compound of claim 1 to a subject in need thereof.
Claim 9 further limits claim 1 to a method of treating fibrosis and/or a disease, disorder, or condition that involves fibrosis, comprising administering the compound of claim 1 to a subject in need thereof.
Claim 10 further limits claim 9 to wherein the fibrosis is at least one selected from a Markush group that includes idiopathic pulmonary fibrosis.
Claim 11 further limits claim 10 to wherein the fibrosis comprises idiopathic pulmonary fibrosis.
An discloses that lysophosphatidic acid (LPA) is a bioactive lipid mediator that plays a role in several cellular functions that can influence many physiological and pathological processes including angiogenesis, wound repair, fibrosis, inflammation and carcinogenesis, and that small molecule compounds that antagonize LPA receptors can be used in the treatment of diseases, disorders or conditions that are dependent on or mediated by LPA (page 1). An also discloses that LPA plays a role in lung fibrosis (page 1). Thus, while the prior art does not explicitly teach that fibrosis is a disease in which LPA is dysregulated, as evidenced by Tager (Tager, et al.; Nature Medicine, v14, pp45-55; 2008), aberrant wound-healing responses to injury have been implicated in the development of pulmonary fibrosis, and lysophosphatidic acid levels increase in bronchoalveolar lavage fluid following lung injury in the bleomycin model of pulmonary fibrosis, and, in persons with idiopathic pulmonary fibrosis, LPA levels in bronchoalveolar lavage fluid were also increased, and inhibition of LPA1 markedly reduced fibroblast responses to the chemotactic activity of this fluid, and therefore LPA1 represents a new therapeutic target for diseases in which aberrant responses to injury contribute to fibrosis, such as idiopathic pulmonary fibrosis (Abstract, page 45). Thus, the patient population to be treated by the method of An appears to be identical to that of instant claim 8. If Applicant disagrees, Applicant is required to show proof of any disqualifying distinction. Applicant is referred to MPEP 2112.01:
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not."
An specifically discloses a method to treat patients suffering from one or more LPA-dependent or LPA-mediated conditions or diseases (page 2, “Summary of the Invention”) and specifically lists idiopathic pulmonary fibrosis as an example of an organ fibrosis for treatment of which a compound disclosed therein is useful (page 6). An further discloses a method of “inhibiting the physiological activity of LPA in a human subject comprising administering a therapeutically effective amount of the present compound or a pharmaceutically acceptable salt thereof to the human subject in need thereof” (page 11). An also discloses “Example 3”, in which the compounds disclosed therein are assayed for inhibition of recombinant human LPA1 receptor, and all compounds disclosed in the invention of An have IC50 of <20 mM in the assay (page 22). Thus, all compounds of the invention of An, including An’s compound 10, effectively inhibit human LPA1 and are useful in the treatment of idiopathic pulmonary fibrosis comprising administering an effective amount of the compound to a subject in need thereof.
Thus, claims 8-11 are anticipated by the disclosure of An.
Claim Rejections - 35 USC § 103
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.
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 1-3, 5-6 and 8-11 are unpatentable over An in view of Patani.
Claims 1-3, 5-6 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over An (WO 2012/100436 A1)3 in view of Patani (Patani, G. A., LaVoie, E. J.; Chemical Reviews, v96, pp3147-3176; 1996).
The limitations of claims 1, 5-6 and 8-11 and the disclosure of An are discussed in the rejection above and hereby incorporated into the instant rejection.
Claim 2 further limits claim 1 to wherein the compound of instant formula (I), has nitrogen as the “X” atom in the central 6-membered ring, thus rendering said ring as a pyridyl ring.
Claim 3 further limits claim 1 to w wherein the compound of instant formula (I), has nitrogen as the “X” atom in the central 6-membered ring, thus rendering said ring as a pyridyl ring, and further requiring that ring A is an isoxazole.
As shown in the table above, compound 10 of the disclosure of An does have an isoxazole as ring A. Compound 10 differs from the scope of instant claims 2-3 in that the 6-membered central ring of compound 10 is a phenyl ring rather than a pyridyl ring. However, a person of ordinary skill in the art would have a reasonable expectation of success in replacing the central phenyl ring of An’s compound 10 with a pyridyl ring, because these ring types are known to be bioisosteric equivalents of one another. For example, see Patani.
Patani teaches that bioisosteric groups are groups with similar physicochemical properties such as electronegativity, steric size, and lipophilicity, and that medicinal chemists have relied on bioisosteric replacements in drug design for many years with an expectation of similar biological activity between compounds where the differences amount to bioisosterically equivalent groups (pages 3147-3148). Patani also teaches that pyridyl and phenyl are ring equivalents. The use of the classical bioisosteres benzene and pyridine resulted in analogues with retention of biological activity within different series of pharmacological agents. One of the successful uses of this replacement resulted in the potent antihistamine mepyramine which evolved by the replacement of the phenyl moiety in antegran by a pyridyl group. Substitution of benzene by pyridine also improved activity in the tricyclic antihistamines promethazine and isothipendyl and neuroleptics promazine and prothipendyl and resulted in a reduction of both sedative and extrapyramidal effects. (page 3158).
Applicant’s invention is unpatentable over the disclosure of An in view of the teaching of Patani, because a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in making and using a derivative of An’s compound 10 having a pyridyl ring in place of the central phenyl ring, because it was known in the art that these rings are bioisosterically equivalent, per the teaching of Patani.
Thus, the invention was prima facie obvious at the time of filing.
Allowable Subject Matter
Claims 4 is 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. Prior art does not teach or reasonably suggest, alone or in combination, any of the specific compounds claimed in instant claim 4.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Cited in Applicant’s Information Disclosure Statement dated 09/06/2024.
2 Methyl 1-((4-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)amino)-3-methylisoxazol-5-yl)phenyl)carbamoyl)-cyclopropanecarboxylate
3 Cited in Applicant’s Information Disclosure Statement dated 09/06/2024.
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