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 1-2, 4, 8-9, 11-17, 19, 21-23, and 27-30 are pending. Claims 1-2, 4, 8-9, 11-17, 19, 21-23, and 27-30 are rejected.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 3/2/2024 has been considered by the Examiner.
Election/Restrictions
Applicant’s election without traverse of ethyl acetate (claim 8) and anti-cholesterol drugs (claim 23) in the reply filed on 5/19/2026 is acknowledged.
Claims 1-2, 4, 8-9, 11-17, 19, 21-23, and 27-30 embrace Applicant’s elected species and are therefore under examination. Applicant’s elected species are not allowable and have been rejected below. Examination was limited for all purposes to the elected species.
Drawings
The drawings are objected to because para. [0024] of the instant specification refers to “Fig. 1A” which does not exist in the drawings. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claim(s) 1, 11-15, and 27-29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Titi et al. (Chem Commun. 2017, 53, 8569-8572).
Regarding instant claim 1, Titi discloses a method of forming a co-crystallized composition (see title, abstract, formation of ionic co-crystals), said method comprising: mixing a first molecule with a second molecule to form a mixture (abstract, the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate was utilized as a liquid-state crystallization agent to form ionic co-crystals using amphoteric azoles; p. 8569, column 2, fourth para. the mixing of a liquid salt with solid), wherein the first molecule is in a solid phase (abstract, amphoteric azoles; p. 8569, column 2, fourth paragraph, the use of neat ILs as co-formers for ionic co-crystals with amphoteric azoles. The uniqueness of this approach lies in the mixing of a liquid salt with solid, molecular co-former to generate new solid-state forms), and wherein the second molecule is in a liquid phase (abstract, the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate; p. 8659, column 2, 4th para. the use of neat ILs as co-formers for ionic co-crystals with amphoteric azoles),
wherein the co-crystallized composition is in the form of a crystalline solid (see abstract-form ionic co-crystals).
Regarding instant claims 11-15, Titi et al. discloses wherein the first molecule (solid) comprises an acidic group capable of donating protons and the second molecule (liquid) comprises a basic group capable of accepting protons (see p. 8570, column 1, 1st para. the azoles used here…. All of them can be protonated, deprotonated and donate and accept hydrogen bonds but differ in acidity, ie. The first molecule comprises an acidic group capable of donating protons, p. 8571, column 1, second para. the [OAc]-,i.e., the second molecule comprises a basic group capable of accepting protons, does interact with the acidic heterocyclic N-H group). Regarding the formation of intermolecular hydrogen bonds, Titi discloses the following on p. 8571, column 1, 2nd para.:
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. The acidic and basic groups described supra lack halogens/halogen bonds.
Regarding instant claim 27, Titi discloses the method of claim 1 wherein the co-crystallized composition is in neutral form (see p. 8571, col. 1, 2nd para. Compound 2…rigidly bound [OAc]-DAOim network, p. 8572, col. 1, 3rd para., 1 and 2 are neutral co-crystals). Regarding instant claim 28, Titi discloses wherein the co-crystalized composition comprises ionic co-crystals of the first molecule and the second molecule (abstract, the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate was utilized as a liquid-state crystallization agent to form ionic co-crystals using amphoteric azoles, see. P. 8569, col. 2, 4th para. the mixing of a liquid salt with solid, molecular co-former to generate new solid-state forms). Regarding instant claim 29, Titi discloses wherein the first molecule of the co-crystallized composition is in anionic form and wherein the second molecule of the co-crystallized composition is in cationic form (abstract; ionic co-crystals, p. 8571, col. 1, 3rd para. the asymmetric unit of 3 bears anionic [DCNim]-and neutral HDCNim entities, in the presence of [C2mim]+ cations (Fig. 3a)).
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.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Titi et al. (Chem Commun. 2017, 53, 8569-8572), in view of Nakach et al. (Int. J. Miner. Process. 74S, 2004, S173-S181).
**The 102 rejection supra over Titi et al. of claims 1, 11-15, and 27-29 is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Titi et al. discloses the method of claim 1, as described under the 102 rejection supra, wherein the mixing comprises the utilization of mechanical force (see p. 8570, column 1, Scheme 1, grinding). Titi does not teach milling specifically.
Nakach examines fine grinding techniques in current use in the pharmaceutical industry (see abstract). Milling is a form of grinding (see title). “The main conclusion reinforces and quantifies current practice of using pancake mills that are preferred for ultra fine grinding as they are simple to use, can treat high feed rates and are easy to clean” (see abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art fails to disclose the process of claim 2, with milling specifically.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 2, it would have been obvious to a skilled artisan to employ milling as a known grinding technique with a reasonable expectation of success in increasing the surface area of the first and second molecule of the instant claims. Milling technologies are widely used in the pharmaceutical industry for griding powders. A PHOSITA would have explored the use of milling in an effort to produce high quality co-crystals.
Claim(s) 4 and 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Titi et al. (Chem Commun. 2017, 53, 8569-8572) as applied to claim 1 above, and further in view of Vasireddi et al. (WO2018029611) and Harbin Medical University (CN105330606- as disclosed on 3/2/2024 IDS).
**The 102 rejection supra over Titi et al. of claims 1, 11-15, and 27-29 is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Titi fails to specifically disclose the following limitation of instant claim 4: “evaporating the added solvent, wherein the mixture is in the form of a liquid at the time of adding the solvent, and wherein the solvent is added after the mixing”.
Vasireddi teaches a process of preparing (dapagliflozin) co-crystals (see abstract). Vasireddi additionally teaches: “The dapagliflozin co-crystals obtained is first neutralized in water and a water immiscible solvent such as ethyl acetate….” (see p. 39, lines 41-42). Vasireddi additionally discloses the following process in claim 67:
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Claim 75 of Vasireddi recites the following: “The process of claim 67, wherein the step e) comprises evaporating the dapagliflozin containing organic layer and crystallizing the reissue with a suitable solvent or a mixture of solvent and antisolvent.” (The previous disclosure teaches ethyl acetate as a suitable solvent, described supra.) Vasireddi fails to disclose the evaporation occurring during a period of at least 6 hours and wherein the evaporating occurs by vaporization.
Harbin Medical University teaches the field of preparing co-crystals (abstract) wherein the evaporating occurs during a period of at least 6 hours (see para. [0020], after 7-30 days by a solvent slow volatilization method).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art fails to specifically disclose “wherein the solvent is added after the mixing”. Additional limitations will be addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 4 and 8, it would have been obvious to a skilled artisan to arrive at the process of adding ethyl acetate (an organic solvent) to the mixture in the process of co-crystallizing with a reasonable expectation of success. Ethyl acetate was a known suitable solvent for the co-crystallization process and a skilled artisan would have been motivated to explore its utility with the instantly claimed “first molecule” and “second molecule”. Regarding the limitation: “wherein the solvent is added after the mixing”, the instant specification does not disclose examples describing superiority or unexpected results regarding the sequential ordering of when the solvent is added. “Selection of any order of mixing ingredients is prima facie obvious”; In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). In the absence of unexpected results, the claimed order of events is prima facie obvious over the prior art wherein the addition of solvent in the co-crystallization process is known, as described supra.
Regarding instant claim 9, a skilled artisan would have been motivated to explore vaporization for a period of at least 6 hours with a reasonable expectation of success in arriving at a co-crystallized composition. It would have been obvious to a PHOSITA to explore such a timeline in an effort to arrive at a functional and stable co-crystallized composition.
Claim(s) 16, 17, 19 and 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Titi et al. (Chem Commun. 2017, 53, 8569-8572) as applied to claim 1 above, in view of Loya et al. (Supramolecular Chemistry, 2019, 1-7-as disclosed on 3/2/2024 IDS).
**The 102 rejection supra over Titi et al. of claims 1, 11-15 and 27-29 is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Titi fails to disclose wherein the first molecule comprises a basic group capable of donating protons and wherein the second molecule comprises an acidic group capable of accepting protons.
Loya et al. in the field of co-crystallization (abstract) teaches wherein a first molecule comprises a basic group capable of donating protons and wherein the second molecule comprises an acidic group capable of accepting protons group (p. 2, column 1, third paragraph, 4-(methylamino)pyridine (4-MetAP), 4-aminopyridine (4-AP), 3-aminopyridine (3-AP), and 2-aminopyridine (2-AP)….BEZA (bezafibrate); p. 3, column 1, first paragraph, the carboxylic acid of BEZA is deprotonated and the pyridyl nitrogen of 4-MetAP is protonated).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art fails to teach a single embodiment of the process of forming a co-crystallized composition wherein the first molecule comprises a basic group capable of donating protons and wherein the second molecule comprises an acidic group capable of accepting protons.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 16, it would have been obvious to a PHOSITA to modify Titi to include wherein a first molecule comprises a basic group capable of donating protons and wherein the second molecule comprises an acidic group capable of accepting protons for the benefit of co-crystallizing and improving stability and efficacy of product. Claim 17 is embraced by the prior art also wherein BEZA comprises a carboxylic acid and 4-aminopyridine, for example, contains an amine group (pictured here for visual:
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).
Regarding instant claim 19, the instantly claimed 2-(methylamino)pyridine (pictured here for visual:
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) is a positional isomer of that of the prior art, 4-(methylamino)pyridine (pictured here for visual:
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). “ ‘Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.’ In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).” See MPEP 2144.09(II). A skilled artisan would have been motivated to explore the use of a positional isomer in the process of co-crystallization with a reasonable expectation of success at arriving at a functional co-crystallized composition.
Regarding instant claims 21-23, BEZA of the prior art is an anti-cholesterol drug and has a molecular weight of more than 200 grams per mole (361.82 g/mol).
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Titi et al. (Chem Commun. 2017, 53, 8569-8572) as applied to claim 1 above, in view of Mohammad et al. (Indian Journal of Science and Technology; 10(6), 2017, 1-5- as disclosed on 3/2/2024 IDS).
**The 102 rejection supra over Titi et al. of claims 1, 11-15 and 27-29 is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Titi fails to explicitly disclose further comprising a step of utilizing the co-crystalized composition as seed crystals to grow additional co-crystallized compositions from the first molecule and the second molecule.
Mohammad is in the field of co-crystals (See abstract) and teaches a step of utilizing a co-crystalized composition as seed crystals to grow additional co-crystallized compositions from a first molecule and a second molecule (abstract, carbamazepine-saccharin (CBZ-SAC) co-crystals; p. 2, column 2, first paragraph, CBZ-SAC co-crystal solution….the crystal was formed….When the temperature of the solution reached 46.05°C (95% of MSZW range), 1.5 wt% seed was added whilst the solution continue to follow the temperature profile with a rate of 0.6 °C/min.)
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment in the prior art of a method of forming a co-crystallized composition of instant claim 1, further comprising a step of utilizing the co-crystalized composition as seed crystals to grow additional co-crystallized compositions from the first molecule and the second molecule.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 30, it would have been obvious to one of ordinary skill in the art to modify Titi to include a step of utilizing a co-crystallized composition as seed crystals to grow additional co-crystallized compositions from a first molecule and a second molecules as taught by Mohammad, for the benefits of arriving at a co-crystallized composition with increased stability and efficacy. A PHOSITA would have been motivated to utilize a seed to impart desired crystal sizes and characteristics optimized by adjusting seed loading and temperature (Mohammad, abstract, p. 2, column 2, 1st para.; p. 3, column 1, 2nd para.) with a reasonable expectation of success at arriving at a useful co-crystallized composition.
Conclusion
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/MEGHAN C HEASLEY/Examiner, Art Unit 1626
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