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 1-55 are pending in the application. Claims 16-21 and 28-37 are rejected. Claims 1-15, 22-27 and 38-55 are withdrawn.
Restriction/Election of Species
Applicant’s election without traverse of Group I, claims 1-37, in the reply filed on December 29, 2025 is acknowledged. Applicant’s further election with traverse of “Form B” for a species of a crystalline form of a compound of Formula I in the reply filed on December 29, 2025 is also acknowledged. The traversal is on the ground(s) that “there is no search and/or examination burden.” See Applicant’s Remarks filed December 29, 2025, page 12 of 13. This is not found persuasive as the instant claims are anticipated by or rendered obvious over the prior art. See rejections under 35 U.S.C. § 102(a)(1) and 35 U.S.C. § 103 below.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-15, 22-27 and 38-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim.
Priority
This application claims benefit of Provisional Application No. 63/350,936, filed on June 10, 2022.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) filed on July 17, 2023 and December 18, 2023 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the Examiner has considered the IDS documents and signed copies of the 1449 forms are attached.
Claim Interpretation
Independent claims 16 and 28 are both drawn towards a crystalline form of a compound of Formula I. However, as discussed below in the rejections under 35 U.S.C. § 112(a) and 35 U.S.C. § 112(b), the instant specification is limited in support for a crystalline form of a compound of Formula I per se (i.e., the non-salt, free base form). Based on evidence in the specification, it appears Applicant’s original intent was for the instant claims to instead be drawn towards a crystalline form of an adipate salt of a compound of Formula I. Accordingly, for the purposes of examination, instant claim 16 and 28 and claims dependent therefrom are being interpreted as being drawn towards the crystalline form (i.e., Form B) of an adipate salt of a compound of Formula I.
Claim Rejections - 35 USC § 112(a)
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 16-21 and 28-37 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.
(Claim Scope) MPEP § 2163 outlines the methodology for determining adequacy of written description. MPEP § 2163(II)(A)(1) instructs “For Each Claim, Determine What the Claim as a Whole Covers”. Instant claims 16 and 28 are both drawn to a crystalline form of a compound of Formula I, wherein the crystalline form is Form B (i.e., Applicant’s elected species).
(Disclosed Support) MPEP § 2163(II)(A)(2) instructs “Review the Entire Application to Understand How Applicant Provides Support for the Claimed Invention Including Each Element and/or Step”. The specification generally discusses the field of endeavor beginning on page 1 including a background on the Rho kinase inhibitor compound, NRL-1049. As indicated in paragraph [0009], NRL-1049 (R) corresponds to the instantly claimed compound of Formula I and has also been previously referred to as BA-1049 (R). In paragraph [0009], Applicant indicates that “the present disclosure provides one or more salts or crystalline forms of a compound of Formula I, having the structure:
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.”
The specification also discloses various crystalline forms (i.e., Form A, Form B and Form C) of the compound of Formula I, which are crystalline polymorphs of the adipate salt of the compound of Formula I. See paragraph [0010]. In addition, the specification provides an X-ray powder diffraction spectrum for each of polymorph Form A, Form B and Form C of NRL-1049 (R) adipate. See FIG. 2, FIG. 6 and FIG. 10 for XRPD spectrum of crystalline Form A, Form B and Form C, respectively. The specification, however, is limited in support for the crystalline form of a neutral, non-salt form of NRL-1049 (R). For instance, although the specification states the instant disclosure is directed to NRL-1049 (R) and crystalline polymorphs thereof (see paragraph [0008]) or provides pharmaceutical formulations comprising crystalline forms of the compound of Formula I (see paragraph [0009]), the specification does not disclose a specific crystalline form (e.g., Form B) for the NRL-1049 (R) free base.
(Determination of Sufficient Support) MPEP § 2163(II)(A)(3) instructs “Determine Whether There is Sufficient Written Description to Inform a Skilled Artisan That Inventor was in Possession of the Claimed Invention as a Whole at the Time the Application Was Filed”. This section of the MPEP further provides the following guidance:
Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
In this situation and as discussed above, Applicant has disclosed support for crystalline Form A, Form B and Form C of the salt (e.g., adipate) of a compound of Formula I. However, Applicant has NOT provided support for the instantly claimed, specific crystalline form (i.e., Form B) of the non-salt form of a compound of Formula I. Accordingly, the disclosure of the instant specification is narrower than the instant claims. Therefore, based on evidence in the specification, a person of skill in the art would not be convinced that Applicant has demonstrated possession of the claimed crystalline Form B of a compound of Formula I. Applicant may overcome this issue of lack of written description by amending both instant claims 16 and 28 to be drawn towards a crystalline form of an adipate salt of a compound of Formula I as opposed to the free base compound of Formula I as recited currently. Dependent claims 17-21 and 29-37 do not correct this issue of a lack of written description and are likewise rejected.
Claim Rejections - 35 USC § 112(b)
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 16 and 28-37 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.
Independent claims 16 and 28 each recite the term “Form B” with respect to the recited “crystalline form of a compound of Formula I” and are rejected as indefinite. The term “Form B” is not defined in each claim and it is unclear how one of ordinary skill could reasonably determine the objective boundaries of the scope of the claim based on the term. A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. In re Musgrave, 431 F.2d 882, 893, 167 USPQ 280, 289 (CCPA 1970). Furthermore, a claim should particularly point out and distinctly claim the subject matter which the Applicant regards as his invention and, under modern claim practice, stand alone to define the invention. MPEP 2173.05(s) states: Where possible, claims are to be complete in themselves. Incorporation by reference is a necessity doctrine, not for applicant’s convenience. Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). Notwithstanding, the instant specification does not appear to provide support for the recited crystalline Form B of a compound of Formula I. Instead, with respect to crystalline polymorphs, the instant specification appears to be limited in scope to a salt (e.g., adipate) of a compound of Formula I but otherwise does not disclose a crystalline polymorph for a compound of Formula I per se. For instance, the XRPD pattern peaks disclosed in paragraphs [0029]-[0032] of the instant specification are related to FIG. 6 which depicts an X-ray powder diffraction spectrum of the crystalline polymorph Form B of NRL-1049 (R) adipate (i.e., an adipate salt of a compound of Formula I) and not NRL-1049 (R) free base. Moreover, for the sake of argument, even if the various embodiments drawn to different XRPD peaks as disclosed in paragraphs [0029]-[0032] of the instant specification were in reference to crystalline Form B of a neutral, non-salt compound of Formula I, it would still be ambiguous as to which of these embodiments Applicant intended the scope of claims 16 and 28 to be defined by. To overcome these issues of indefiniteness, it is suggested Applicant amend both claims 16 and 28 to be drawn towards a crystalline form of an adipate salt of a compound of Formula I. As stated above, for the purposes of examination, claims 16 and 28 are being interpreted as being drawn towards an adipate salt of the recited compound of Formula I. Dependent claims 29-37 do not correct these issues of indefiniteness and are likewise rejected.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. § 112(d):
(d) REFERENCE IN DEPENDENT FORMS — Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. § 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 29-32 are rejected under 35 U.S.C. § 112(d) or pre-AIA 35 U.S.C. § 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 29 recites “the crystalline form is a salt” but is also drawn towards the crystalline form of a compound of Formula I as recited in parent claim 28. As discussed above, parent claim 28 is drawn towards a crystalline form of a compound of Formula I and NOT a crystalline form of a salt (e.g., adipate) of a compound of Formula I. Therefore, claim 29 fails to further limit the subject matter of parent claim 28. Dependent claims 30-32 do not correct for this improper dependent form and are likewise rejected.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 16-18 and 21 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by U.S. PGPub. No. 2020/0199105 A1 (June 25, 2020).
The prior art teaches compound “BA-1049 (R)” which corresponds to the instantly claimed compound of Formula I as recited in instant claim 16. See e.g., Fig. 21A.
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Regarding instant claims 16-18 and 21, the prior art discloses a “graphic representation of X-Ray powder diffraction analysis traces of BA-1049 (R) adipate” (reproduced below). See e.g., Fig. 21A, FIG. 27 and paragraph [0074].
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Note: As discussed above, instant claim 16 is being interpreted as being drawn towards the adipate salt of a compound of Formula I as this appears to have been Applicant’s intent. With respect to “Form B” as recited in claim 16, the instant disclosure states “Form B is characterized by an XRPD pattern having a peak expressed in degrees 2Ɵ (±0.2) of about 17.2 and about 23.8.” See paragraph [0030] of the instant specification. Accordingly, the prior art teaches the instantly claimed XRPD pattern peaks, in °2Ɵ (±0.2), of about 17.2 and about 23.8 as indicated below.
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Regarding the limitations of instant claim 21, the claimed DSC requirement is considered to be a characteristic which would necessarily be present in the claimed crystalline Form B of a compound of Formula I and is, therefore, non-limiting. “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01(II).
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.
Claims 28-37 are rejected under 35 U.S.C. § 103 as being unpatentable over U.S. PGPub. No. 2020/0199105 A1 (June 25, 2020).
Determining the scope and contents of the prior art (See MPEP § 2141.01)
The prior art teaches compound “BA-1049 (R)” which corresponds to the instantly claimed compound of Formula I as recited in instant claim 28. See e.g., Fig. 21A.
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Regarding instant claims 28-32, the prior art discloses a “graphic representation of X-Ray powder diffraction analysis traces of BA-1049 (R) adipate” (reproduced below). See e.g., Fig. 21A, FIG. 27 and paragraph [0074]. The prior art also teaches pharmaceutical formulations of BA-1049 (R) and/or adipate salts thereof and/or deuterated form thereof. See e.g., paragraph [0100].
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Note: As discussed above, instant claim 28 is being interpreted as being drawn towards the adipate salt of a compound of Formula I as this appears to have been Applicant’s intent. With respect to “Form B” (i.e., Applicant’s elected species) as recited in claim 28, the instant disclosure states “Form B is characterized by an XRPD pattern having a peak expressed in degrees 2Ɵ (±0.2) of about 17.2 and about 23.8.” See paragraph [0030] of the instant specification. Accordingly, the prior art teaches the instantly claimed XRPD pattern peaks, in °2Ɵ (±0.2), of about 17.2 and about 23.8 as indicated below.
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Ascertainment of the differences between the prior art and the claims (See MPEP § 2141.02)
Regarding instant claims 28-37, the prior art does not specifically teach a pharmaceutical formulation having crystalline BA-1049 (R) adipate or the instantly claimed crystalline Form B percentage requirements (i.e., 95%, 98%, 99%, 99.5%, 99.9% and 99.99%).
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 28-37, it would, however, have been obvious based on the teachings of the prior art for a person of ordinary skill in the art to arrive at the claimed pharmaceutical formulation with the claimed Form B crystalline percentages. Considering that the prior art teaches both the instantly claimed crystalline Form B of a compound of Formula I (e.g., see XRPD pattern of crystalline BA-1049 (R) adipate as disclosed in FIG. 27) and pharmaceutical formulations of BA-1049 (R) and/or adipate salts thereof and/or deuterated form thereof (e.g., see paragraph [0100]), it would be considered within the ability of a skilled artisan to apply the prior crystalline BA-1049 (R) adipate in a pharmaceutical formulation. Furthermore, a skilled artisan would recognize the benefit(s) of obtaining the highest level of one specific crystalline form (e.g., Form B) with respect to the prior art crystalline BA-1049 (R) adipate. At least in the interest of applying the purer product in downstream applications such as “further analysis of crystallinity and physical properties via X-ray powder diffraction (XRPD), water absorption by hygroscopicity, melting point and other physicochemical parameters” (see e.g., paragraph [0306]), a person of ordinary skill would have been motivated to arrive at the instantly claimed crystalline percentages based on the teachings of the prior art. MPEP § 2144.04(VII) states: Purer forms of known products may be patentable, but the mere purity of a product, by itself, does not render the product nonobvious. Therefore, instant claims 28-37 are prima facie obvious over the prior art.
Conclusion
No claims are allowed.
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/D.M.S./Examiner, Art Unit 1626
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626