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
The listing of claims filed 03 April 2024 has been reviewed.
Claims 1-47 are pending.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 07 August 2024 is acknowledged and has been considered. Any lined-through references have not been considered and must be submitted or resubmitted in proper format for consideration. Specifically, a copy of an NPL document (“European Drug Discovery Innovation & Outsourcing Programme – Barcelona, Spain, 12 – 13 September 2023; Blaszczyk. R., Arginase ½ inhibitor OATD-02: from discovery to first in-man setup in cancer immunotherapy.”) is missing.
Priority
The instant application, filed 03 April 2024, claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/494,557, filed 06 April 2023, and priority to PLP.444342, filed 06 April 2024. Acknowledgment is made of Applicant’s claim to the benefit of an earlier filing date. However, a certified copy of the priority document PLP.444342 has not been received.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “…MeOLi suspended in the second solvent, at elevated temperature….” Examiner suggests adding “an” immediately prior to “elevated.”
Appropriate correction is requested.
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 1-46 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.
Claims 1, 8, 10, 19, 27, and 29 recite the limitations "the first solvent," “the second solvent,” “the third solvent,” and/or “the fourth solvent.” There is insufficient antecedent basis for these limitations in the claims because, for example, it is unclear whether “the first solvent” refers to some newly recited solvent of step c) or a previously recited solvent of steps a) or b). Claim 1 further recites the term “at elevated temperature”. However, the claim does not provide guidance as to what the recited temperature is elevated is with respect to. The specification does not define “elevated temperature”, so the term is considered to be a relative term. A person having ordinary skill in the art would not be reasonably apprised of the scope of the invention. See MPEP 2173.05(b)
Claims 2, 4-5, 7, 10-11, 20, 22-23, 25, and 29-30 use the phrase "preferably," which renders these claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 44 contains the trademark/trade name DOWEX®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the ion-exchange resin and, accordingly, the identification/description is indefinite. Examiner suggests removing the trademarked term from claim 44.
Claims 3, 6, 9, 12-18, 21, 24, 26, 28, 31-43, and 45-46 are rejected due to their dependency on rejected claims 1 or 19 because claims 3, 6, 9, 12-18, 21, 24, 26, 28, 31-43, and 45-46 inherit the 112(b) rejection of claims 1 and 19 without rectifying the issue.
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.
Claim 46 is 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 46 is drawn to, “The process of claim 19, wherein the sequence steps of (g), (h), [and] (i) is replaced by the sequence comprising…” Thus, claim 46 does not include all the limitations of claim 19, upon which claim 46 depends. For example, step (i) in claim 19 recites quenching the reaction using saturated aqueous sodium carbonate, but this limitation is absent from claim 46.
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.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
Claims 1-18 are drawn to a process for the preparation of methyl (1R,2R,4R)-2-acetamido-2-(tert-butylcarbamoyl)-4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl)cyclohexane-1-carboxylate of formula 11.
Claims 19-46 are drawn to a process for the preparation of the solid crystalline solid crystalline (1R,2S,5R)-1-amino-5-[2-(dihydroxyboranyl)ethyl]-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid of formula 1.
Close prior art to claims 1-46 includes Blaszczyk (WO 2017/191130 A2). Blaszczyk discloses (1R,2S,5R)-1-amino-5-[2-(dihydroxyboranyl)ethyl]-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid, which is identical to the compound of formula 1 (p. 177, Example 43; p. 268, Ex. No. 38; p.33, Example No. 17), as well as compounds similar to the compound of formula 11 (p.253, Example 68):
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Furthermore, Blaszczyk discloses methods by which such exemplary compounds may be synthesized (p. 75, Paragraph [0242]). However, Blaszczyk does not disclose the same reaction intermediates as those recited in the instantly claimed process. For example, Blaszczyk uses an alkene-containing intermediate (p. 102, Example 10; p. 113, Example 17):
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In contrast, the closest intermediate compound in the instantly claimed process is the compound of formula 8, which has a haloalkyl. Thus, while the synthesis methods disclosed by Blaszczyk and the instantly claimed processes are similar, Blaszczyk contains no suggestion to make modifications to the disclosed synthesis methods which would result in the instantly claimed processes. The instantly claimed process differs from Blaszczyk in the following respects:
Step A. described by Blaszczyk involves producing ethyl 2-oxocyclohex-3-ene-1-carboxylate from 2-cyclohexen-1-one, which already has a ketone group (p. 113, Paragraphs [0375-0376]). However, in the claimed process step a) involves (S)-2-(1,4-dioxaspiro[4.5]decan-7-yl)ethan-1-ol, which already has a hydroxyalkyl group, and a ketone is introduced later in step b). Thus, the sequence in which different functional groups are added varies between Blaszczyk’s method and the claimed method.
The reactions by which the pinacolborane group is added differs. In the claimed process, the compound of formula 8 is dissolved in a mixture containing triphenylphosphine, B2(pin)2, CuI, and MeOLi. However, in the method disclosed by Blaszczyk, rac-(1R, 2S, 5R)-1-acetamido-N-(tert-butyl)-2-((dimethylamino)methyl)-5-vinylcyclohexane-1-carboxamide is dissolved in DCM and 4,4,5,5-teramethyl-1,3,2-dioxaborolane [pinacolborane] was added and, subsequently, an iridium catalyst is utilized. The reaction product yielded after adding a pinacolborane group in Blaszczyk’s process is rac-(1R, 2S, 5R)-1-acetamido-N-(tert-butyl)-2-((dimethylamino)methyl)-5-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl)cyclohexane-1-carboxamide (Paragraph [0389]).
Additionally, Blaszczyk does not disclose compounds of formulas 6, 7, 8, 9, or 10 or involve using such compounds as reaction intermediates. Accordingly, various reaction catalysts and reagents used Blaszczyk differ from those recited by the claimed process.
Thus, multiple changes to Blaszczyk’s synthesis method would have been required and a skilled artisan would not have had a reasonable expectation of success in making all the necessary modifications to each step which would have resulted in the instantly claimed process.
Claim 47 is drawn to solid crystalline (1R,2S,5R)-1-amino-5-[2-(dihydroxyboranyl)ethyl]-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid of formula 1 in anhydrous form A, that is characterized by at least one of the following:
XRPD peaks at 7.39, 8.55, 9.49, 12.83, 14.71, 16.86, 17.37, 17.88, 19.11, 19.88, 20.55, 21.19, 22.18, 22.87, 23.66, 24.52, 25.73, 26.09, 26.94, 28.19, 28.61, 28.88, 29.69, 30.28, 31.45, 32.02, 33.06, 33.36, 34.05, 34.52, 35.15, 36.20, 37.52, 38.95, 40.54, and 41.76;
IR bands at 3134, 2992, 2918, 2859, 2826, 2789, 2764, 2727, 1584, 1522, 1458, 1404, 1369, 1344, 1310, 1263, 1202, 1159, 1105, 1074, 1028, 993, 887, 845, 762, and 731 cm⁻¹; and
DSC trace with two broad endothermic events: onset at 141.9°C and peak at 173.7°C; onset at 237.4°C and peak at 254.1°C.
Close prior art includes Blaszczyk (WO 2017/191130 A2). Blaszczyk discloses (1R,2S,5R)-1-amino-5-[2-(dihydroxyboranyl)ethyl]-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid (p. 177, Example 43; p. 268, Ex. No. 38). However, Blaszczyk does not indicate whether the instantly claimed compound is in solid crystalline form, nor does Blaszczyk disclose its XRPD peaks, IR bands, or DSC trace. A skilled artisan could not have predicted the instantly claimed solid crystalline (1R,2S,5R)-1-amino-5-[2-(dihydroxyboranyl)ethyl]-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid having the recited characteristics. Furthermore, there is no evidence that the prior art compound disclosed by Blaszczyk is inherently the same crystalline form as is instantly claimed. This is because the process by which (1R,2R,5R)-1-amino-5-(2-boronoethyl)-2-((dimethylamino)methyl)- cyclohexane-1-carboxylic acid dihydrochloride is synthesized as disclosed by Blaszczyk (p. 118, Example 18) differs from the method disclosed by the instant application. Specifically, the synthesis steps taught by Blaszczyk are the same as those discussed above in regards to instant claims 1-46. Additionally, steps k) and l) in the claimed process involve extracting the compound of formula 5 in aqueous 6 M HCl, which is similar to the process disclosed by Blaszczyk wherein 6 N HClaq is used and the mixture is subsequently purified by ion exchange chromatography on DOWEX® (p. 118, Paragraph [0395]). However, the preceding steps in the process taught by Blaszczyk and the claimed process differ. Consequently, the claimed solid, crystalline compound is formed under different conditions than the compound described by Blaszczyk, so the instantly claimed crystalline form would not have inherently been produced.
Conclusion
Claims 1-2, 4-5, 7-8, 10-11, 19-20, 22-23, 25, 27, 29-30, and 44 are rejected under 35 U.S.C. 112(b).
Claims 3, 6, 9, 12-18, 21, 24, 26, 28, 31-43, and 45-46 are rejected due to their dependency on rejected claims 1 or 19 because claims 3, 6, 9, 12-18, 21, 24, 26, 28, 31-43, and 45 inherit the 112(b) rejection of claims 1 and 19 without rectifying the issue.
Claim 46 is rejected under 35 U.S.C. 112(d)
Claim 47 is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C 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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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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