DETAILED ACTION
Claims 1-11 and 15-21 are currently pending in the instant application.
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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to claims 1-7, 11 and 17 with election of free acid crystal form A, found in claim 2, in the reply filed on 06/10/2026 is acknowledged. The traversal is on the ground(s) that the claimed structural formula, the common feature shared among Groups I-III, provides a structurally significant distinction over CN 103097358. CN ‘358 teaches compound
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and the claimed compound has significantly superior EP4 antagonistic activity and enhanced binding affinity for the EP4 receptor compared to the control compound.
This is not found persuasive because as discussed in the following 103(a) rejection, a crystal form of a compound of formula
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would not be considered a structurally significant distinction over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-10, 15-16 and 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/10/2026.
Priority
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Information Disclosure Statement
Applicant's Information Disclosure Statement filed on 02/27/2024 has been considered. Please refer to Applicant's copies of the 1449 submitted herewith.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 2, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Specifically claim 2 recites
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as well as under condition (1) after a TGA curve, and “preferably about”. Additionally claim 4 recites “preferably, the pharmaceutically acceptable salt” at the end of p. 4 of the claims. Claim 5 also recites preferably in line 8 of the claim, as well as in condition (1) a TGA curve, and “more preferably” at the end of p. 5 of the claims. Further claim 6 recites “preferably, the crystal form A” after the first full paragraph of the claim and “preferably” twice under condition (1) a TGA curve, condition (2) a DSC curve, and at the beginning of the last paragraph of claim 6.
Regarding claims 2 and 4-6, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 2 recites e.g.
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. There are multiple instances of “e.g.” are found throughout claim 4. Claims 5-6 recite e.g. under the condition (1) a TGA curve of the crystal form A.
Regarding claim 4, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “or the free acid
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,” and the claim also recites “further, the free acid
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” which is the narrower statement of the range/limitation. The claim also recites “
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” as well as “
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”. It is unclear if the term “further”, “furthermore” and “still further” can be interpreted as “or” or “and”. If these terms are interpreted as “and”, then the claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. This rejection may be overcome be replacing the terms “further”, “furthermore” and “still further” with “or”.
Similarly claims 3 and 5-7 also recite the terms “further”, “furthermore” and “still further” throughout the claims and are also rejected.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation
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, and the claim also recites
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which is the narrower statement of the range/limitation.
Claim 6 recites the broad recitation
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, and the claim also recites
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.
Claim 6 recites at (1) TGA curve “showing a weight loss of about 0.50%-3.00%”, “and showing a weight loss of about 2.00%-5.00%”, etc. The claim contains various different numerical ranges for the same item. This is ambiguos because the claim boundaries are not clearly defined. The same ambiguity is found at (2) DSC curve.
In claims 5 and 6, it states that FIG. 9 and FIG. 13 is drawn to a 1H NMR spectrum of the crystal form A of tromethamine salt or diethylamine salt of the compound of Formula I. However, FIG. 9 and FIG. 13 show the 1H NMR spectrum of the molecular structure in solution (i,e, the compound is dissolved in a solvent such as CD3OD). Thus FIG. 9 and FIG. 13 do not necessarily correspond to the solid-state arrangement of the crystalline form, since studying the crystal itself without dissolving it would require a solid-state NMR spectrum. Thus FIG. 9 and FIG. 13 do not provide data that is a 1H NMR spectrum of the crystal form A of tromethamine salt or diethylamine salt of the compound of Formula I. As a result, FIG. 9 and FIG. 13 do not narrow claim 5 or 6, respectively.
Regarding the spectral data of claims 5-6, MPEP 2173.05(s) Reference to Figures or Tables states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parteFressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
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.
Claim(s) 1, 4, 11 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over SPYVEE (see US Pat. No. 8,686,018, pub. 04/01/2014) and further in view of DATTA (see Nature Reviews, Drug Discovery, 2004, Vol. 3, p. 42-57).
SPYVEE teaches compounds of formula
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(see col. 8) with compounds such as
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(see col. 49) exemplified. The compounds are taught in pharmaceutical compositions (see col. 8, lines 60-65) and may include pharmaceutically acceptable salts thereof (see col. 3, line 6). The exemplified compound corresponds to a compound of formula I
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except that rather than having R4 as CF2CH3, R4 is CF2H. However, substituting a CH3 for a H in the compound of the prior art (example 32), one would arrive at the compound of the instant claims. Compounds of the same structural formula that differ only by the replacement of a methyl for a hydrogen atom would be obvious. As stated in re Wood, 199 USPQ 137, hydrogen and methyl are deemed obvious variants, and substitution of a methyl for the hydrogen (i.e. substitution of CH3 for H) in the compound of SPYVEE would give rise to the compounds of the instant claims. One would be motivated to synthesize a compound wherein R4 is CF2CH3 rather than CF2H to find further compounds that suppress PGE2/EP4. The motivation to make the claimed compound derives from the expectation that structurally similar compounds are generally expected to have similar properties and similar utilities. Further, there is close structural similarity of the instantly claimed compounds to the prior art compounds and the common utility shared among the compounds. There is an expectation among those of ordinary skill in the art that similar structural compounds will have similar properties and that modification of a known structure is mere experimentation within the means of a skilled artisan. See MPEP 2144.09(I).
DATTA teaches that pharmaceutical solids can be classified as either crystalline solids or amorphous solids. Most marketed pharmaceuticals consist of molecular crystals as arrangement of molecules in a crystal determines its physical properties and, in certain cases, its chemical properties, and so greatly influences the processing and formulation of solid pharmaceuticals as well as key drug properties such as dissolution rate and stability (see p. 42). Amorphous solids often have desirable pharmaceutical properties – such as faster dissolution rates – than their crystalline counterparts but are not marketed as widely as the crystalline forms because of their lower chemical stability and innate tendency to crystallize (see p, 42, 1st column).
Prior to the filing of the instant application, a person of ordinary skill in the art following the teachings of SPYVEE would have found it prima facie obvious to synthesize the instantly claimed compound to find other compounds that serve to suppress PGE2/EP4 signaling for treatment of inflammatory autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Further as DATTA teaches, pharmaceutical compounds are often formed as crystals in order to modify drug properties such as dissolution rate and stability. Thus, it would be obvious to form the crystal form of said compound in order to maximize properties such as dissolution rate, stability and even bioavailability.
Rejection II
Claims 1, 4, 11 and 17 is/are rejected under 35 U.S.C. 103 as being obvious over ZHANG et al (See US PG Pub No. 2023/0125494, pub. 04/27/2023 and filed 03/04/2021 further in view of DATTA (see Nature Reviews, Drug Discovery, 2004, Vol. 3, p. 42-57).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
ZHANG et al teach compounds of formula
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with specific compound
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(see col. 4 and paragraph [0359], p. 43 as compound I-19) taught. The compound is taught as a selective EP4 antagonist which may be useful in the treatment of arthritis (see paragraph [0005], p. 1) and for treatment of EP4-related disease (see paragraph [0038], p. 8). The compound is taught as a salt (see paragraph [0010], p. 2 or claim 6, p. 87) and in a pharmaceutical composition (see claim 7, p. 92). ZHANG et al does not teach crystal form of the compound.
DATTA teaches that pharmaceutical solids can be classified as either crystalline solids or amorphous solids. Most marketed pharmaceuticals consist of molecular crystals as arrangement of molecules in a crystal determines its physical properties and, in certain cases, its chemical properties, and so greatly influences the processing and formulation of solid pharmaceuticals as well as key drug properties such as dissolution rate and stability (see p. 42). Amorphous solids often have desirable pharmaceutical properties – such as faster dissolution rates – than their crystalline counterparts but are not marketed as widely as the crystalline forms because of their lower chemical stability and innate tendency to crystallize (see p, 42, 1st column).
Prior to the filing of the instant application, a person of ordinary skill in the art following the teachings of DATTA would have found it prima facie obvious to form a crystalline solid of the compound of ZHANG et al since DATTA teaches that pharmaceutical solids are often formed as crystals in order to modify drug properties such as dissolution rate and stability. As the compounds of ZHANG et al are taught to function as selective EP4 antagonist and be useful in the treatment of arthritis, it would be obvious to form the crystal form of said compound in order to maximize properties such as dissolution rate, stability and even bioavailability.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 11 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 8-11 of U.S. Patent No. 12,643,889 (hereafter referred to as ‘889) in view of DATTA (see Nature Reviews, Drug Discovery, 2004, Vol. 3, p. 42-57).
US Pat. No. ‘889 is drawn to compounds of formula
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with claims 8 and 12 teaching the instantly claimed compound
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. Further the pharmaceutically acceptable salt of the compound is taught (see claims 1, 8 and 12) as well as a pharmaceutical composition (see claim 6).
DATTA teaches that pharmaceutical solids can be classified as either crystalline solids or amorphous solids. Most marketed pharmaceuticals consist of molecular crystals as arrangement of molecules in a crystal determines its physical properties and, in certain cases, its chemical properties, and so greatly influences the processing and formulation of solid pharmaceuticals as well as key drug properties such as dissolution rate and stability (see p. 42). Amorphous solids often have desirable pharmaceutical properties – such as faster dissolution rates – than their crystalline counterparts but are not marketed as widely as the crystalline forms because of their lower chemical stability and innate tendency to crystallize (see p, 42, 1st column).
A person of ordinary skill in the art following the teachings of DATTA would have found it prima facie obvious to form a crystalline solid of the compound of US Pat. No. ‘889 et al since DATTA teaches that pharmaceutical solids are often formed as crystals in order to modify drug properties such as dissolution rate and stability. As the compounds of US Pat. No. ‘889 are taught to treat colorectal cancer, it would be obvious to form the crystal form of said compound in order to maximize properties such as dissolution rate, stability and even bioavailability.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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 supervisor, Adam Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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