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
This office action is in response to applicant’s communication filed on 5/21/26. Claims 1-20 are pending in this application.
Applicant's election with traverse of Group 1, claims 1-9 and 13-20, in the reply filed on 5/21/26 is acknowledged. The traversal is on the ground(s) that the Office Action has not established that it would pose an undue burden to examine the full scope of the claims. This is not found persuasive because the claims of the various groups are divergent in subject matter and are classified separately.
Claims 10-12 are withdrawn from consideration being drawn to the non-elected invention.
Applicant’s election of the following compound is acknowledged herewith:
(R)-L4
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The elected species is understood as the (R)-L4 chiral bisphosphine ligand species shown in claim 5, corresponding to the BTFM-Garphos type ligand. Accordingly, the claims have been searched solely to the extent of the species as shown herein. The search has not been extended to determine the patentability of the other species encompassed by the claims.
Claims 1-9 read on the elected species. Thus claims 13-20 are withdrawn as being non-readable on the elected species.
As a result, claims 1-9 are being examined in this Office Action and claims 10-20 are withdrawn.
Priority
The applicant claims benefit as follows:
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Objections
Claims 4, 5 and 9 are objected to because of the following informalities:
Claim 4 is objected to because claim 1 recites “palladium catalyst,” while claim 4 recites “said palladium catalysts.”
Claim 5 is objected to because claim 1 recites “chiral bisphosphine ligand,” while claim 5 recites “said chiral diphosphine ligand.”
Claim 9 is objected to because claim 1 recites “organic additive,” while claim 9 recites “organic additives.”
Appropriate correction is required.
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.
Claims 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 is indefinite because of the claim language “the tertiary propargyl alcohol with different substituents.” The phrase “the tertiary propargyl alcohol” lacks antecedent basis. It is further unclear whether the phrase “different substituents” requires R1, R2 and R3 to be different from each other, or whether the phrase merely refers to different possible tertiary propargyl alcohol starting materials within the genus. Thus, the metes and bounds of the claimed tertiary propargyl alcohol are unclear.
Claim 1 is also indefinite because of the claim language “highly optically active.” The specification states that the reaction has high enantioselectivity, such as 77% ee to 96% ee, but the claims do not recite any numerical enantiomeric excess, optical purity, or other objective standard for determining what degree of optical activity constitutes “highly optically active.” Thus, one would not know what is included and what is excluded from the scope of “highly optically active.”
Claim 3 is indefinite because of the claim language “putting the reaction tube in the preset low-temperature bath at -20 ~80°C or oil bath” and “raising the reaction tube from the oil bath.” The claim first recites either a low-temperature bath or an oil bath, but later requires raising the reaction tube from “the oil bath.” It is unclear whether the reaction tube must be placed in a low-temperature bath or an oil bath, and “the oil bath” lacks clear antecedent basis when the low-temperature bath is used. It is further unclear how a temperature range extending to 80°C constitutes a “low-temperature bath.” Thus, the metes and bounds of the claimed reaction temperature condition are unclear.
The dependent claims are rejected as being dependent on a rejected claim. Appropriate correction is required.
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. See 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.2d438, 164 USPQ 619 (CCPA 1970); and 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-9 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of Ma et al. (US 11,623,907 B2, issued April 11, 2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are drawn to a method of directly constructing highly optically active axial chirality-containing allenoic acid compounds by reacting tertiary propargyl alcohol, carbon monoxide and water in solvent under the action of a palladium catalyst. The patented claims of Ma et al. recite the same general reaction scheme for preparing optically active tetrasubstituted allenoic acid compounds from tertiary propargyl alcohol, carbon monoxide and water using a palladium catalytic system.
The instant claims are likewise drawn to a method for preparing a chiral tetra-substituted allenoic acid compound based on a palladium catalytic system, wherein tertiary propargyl alcohol, carbon monoxide and water react in the presence of a palladium catalyst, chiral bisphosphine ligand, organophosphoric acid, organic additive, and organic solvent. The instant claims merely recite obvious variants of the same general palladium-catalyzed preparation of optically active tetrasubstituted allenoic acid compounds. The use of the elected (R)-L4 chiral bisphosphine ligand and organic additive would not render the instant claims patentably distinct from the patented claims because such catalyst and ligand selections are directed to routine optimization of the same palladium-catalyzed allenoic acid-forming process.
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 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 of this title, 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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (“Tetrasubstituted allenes via the palladium-catalysed kinetic resolution of propargylic alcohols using a supporting ligand,” Nature Catalysis, Vol. 2, November 2019, pages 997-1005; in applicant’s IDS filed 10/31/23), in view of Abdur-Rashid et al. (US 2013/0184479 A1, published July 18, 2013) and further in view of Strem Chemicals, Inc., “Garphos™ Ligand Kit,” GarphosKit0711, July 2011.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Zheng et al. teaches a straightforward catalytic asymmetric synthesis of tetrasubstituted 2,3-allenoic acids from readily available racemic propargylic alcohols. Zheng et al. teaches the co-catalysis of palladium and a Brønsted acid in the presence of a commercially available chiral ligand, DTBM-SEGphos, and an achiral monophosphine supporting ligand, PPh3, wherein the kinetic resolution of propargylic alcohols proceeded efficiently in the presence of water and 1 atm CO, affording tetrasubstituted 2,3-allenoic acids in excellent enantioselectivity and atom economy with good functional group compatibility. Zheng et al. further teaches that these allenes are precursors to compounds with quaternary carbon centres and other chiral tetrasubstituted allene building blocks. See the reaction scheme in Figure 2 below as an example. (Zheng et al., page 997, Abstract; Figure 2, page 999)
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Zheng et al. teaches that racemic propargylic alcohols are common chemicals and would be the most straightforward starting point to creating optically active tetrasubstituted allenes. Zheng et al. teaches applying a commercially available chiral ligand, DTBM-SEGphos, with Brønsted acid, forming a transient leaving group, and teaches that the key is the addition of PPh3 as a supporting ligand. (Zheng et al., page 997)
Zheng et al. teaches screening various commercially available chiral ligands for the asymmetric carboxylation reaction of 2-phenyloct-3-yn-2-ol with (PhO)2POOH to form a transient leaving group. Zheng et al. found that the addition of supporting ligand PPh3 led to a dramatic and unexpected enhancement in enantioselectivity. Zheng et al. teaches that the enantioselectivity was improved by increasing the loading of water and PPh3, and that (PhO)2POOH was found to be most efficient in activating the hydroxyl group after examining different Brønsted acids. See Table 1 below. (Zheng et al., pages 997-998, Table 1)
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Zheng et al. teaches optimal reaction conditions including PdCl2, DTBM-SEGphos, (PhO)2POOH, PPh3, H2O, toluene, -5° C., and 1 atm CO, affording the desired allenoic acid in 41% NMR yield with 94% ee. Zheng et al. further teaches that a variety of racemic tertiary propargylic alcohols bearing electron-neutral, electron-rich and electron-deficient aryl moieties smoothly underwent the transformation, forming tetrasubstituted chiral 2,3-allenoic acids in good yields with over 90% ee, and alkyl R2 groups such as t-Bu, cyclohexyl and n-propyl also afforded the desired products with high enantioselectivities. (Zheng et al., page 998)
Abdur-Rashid et al. teaches biaryl diphosphine ligands and the use of the ligands in metal catalysts for asymmetric synthesis. Abdur-Rashid et al. teaches that transition metal complexes used for asymmetric synthesis include metals such as ruthenium, rhodium, iridium, palladium, etc., coordinated with a tertiary phosphine compound as a catalyst. Abdur-Rashid et al. further teaches that numerous chiral diphosphine compounds having various structures had been developed, including BINAP, DuPhos, BPE, SEGPHOS, BIPHEMP, HexaPHEMP, P-Phos and MeO-BIPHEP. (Abdur-Rashid et al., Abstract and paragraphs 0001-0003)
Abdur-Rashid et al. teaches that for applications in industrial asymmetric catalysis, a metal catalyst comprising a transition metal complex of a chiral ligand must exhibit high activity and enantioselectivity for the desired transformation of a particular substrate, and that the chiral ligand and its precursors can be prepared efficiently by an optimized synthetic route amenable to scale-up. Abdur-Rashid et al. also teaches that the 6,6’-alkoxy groups of the ligand impart atropisomerism while the 4,4’-alkoxy groups facilitate enhanced stereoselectivity and activity of catalysts derived from these compounds. (Abdur-Rashid et al., paragraphs 0005 and 0007)
Abdur-Rashid et al. teaches metal complexes incorporating biaryl diphosphine ligands of Formula (B), useful in a variety of catalytic processes including asymmetric hydrogenation of a variety of prochiral substrates. Abdur-Rashid et al. teaches that the catalytic reactions include hydrogenation, transfer hydrogenation, hydroformylation, hydrosilylation, hydroboration, hydroamination, hydrovinylation, hydroarylation, hydration, oxidation, epoxidation, C-C bond formation, C-X bond formation, functional group interconversion, kinetic resolution, dynamic kinetic resolution, cycloaddition, Diels-Alder reaction, retro-Diels-Alder reaction, sigmatropic rearrangement, electrocyclic reaction, olefin metathesis, polymerization, carbonylation and aziridination. Abdur-Rashid et al. also teaches that the transition metal complexes containing compounds of Formula (B) include any metal having catalytic activity, such as iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver or gold. See the structure of compounds of Formula (B) below. (Abdur-Rashid et al., paragraphs 0031 and 0054-0061)
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Strem Chemicals teaches a Garphos™ Ligand Kit, GarphosKit0711, July 2011, listing (R)-BTFM-Garphos™, catalog number 15-1663, and (S)-BTFM-Garphos™, catalog number 15-1664, as Garphos ligand components. Strem Chemicals identifies (R)-BTFM-Garphos™ as (R)-2,2’-Bis[bis(3,5-trifluoromethylphenyl)phosphino]-4,4’,6,6’-tetramethoxybiphenyl, min. 97%, and further identifies the corresponding (S)-BTFM-Garphos™ compound. Strem Chemicals also teaches the Garphos ligand family as chiral ligands used in the preparation of hydrogenation catalysts with exceptionally high activity and selectivity. See figures below. (Strem Chemicals, GarphosKit0711, pages 1-2)
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Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Zheng et al. is deficient in the sense that it does not expressly teach the elected (R)-L4, BTFM-Garphos type, chiral bisphosphine ligand.
Instead, Zheng et al. teaches using DTBM-SEGphos as the chiral ligand with PPh3 as a supporting ligand in the palladium/Brønsted acid catalyzed carboxylation of propargylic alcohols with CO and water to provide tetrasubstituted allenoic acids. (Zheng et al., pages 997-998)
Abdur-Rashid et al. and Strem Chemicals cure this deficiency by teaching the Garphos/BTFM-Garphos family of chiral biaryl diphosphine ligands for asymmetric metal catalysis. Abdur-Rashid et al. teaches that biaryl diphosphine ligands are useful in metal catalysts for asymmetric synthesis and that the catalytic transformations include kinetic resolution, dynamic kinetic resolution and carbonylation using transition metals including palladium. Strem Chemicals teaches the commercial availability and identity of the (R)-BTFM-Garphos ligand. (Abdur-Rashid et al., paragraphs 0001, 0005, 0054-0061; Strem Chemicals, GarphosKit0711, pages 1-2)
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention to substitute Zheng et al.’s commercially available chiral bisphosphine ligand, DTBM-SEGphos, with the known commercially available chiral biaryl diphosphine ligand (R)-BTFM-Garphos, as taught by Abdur-Rashid et al. and Strem Chemicals, in the palladium/Brønsted acid catalyzed carboxylation of tertiary propargylic alcohols with carbon monoxide and water.
Zheng et al. expressly teaches screening commercially available chiral ligands and optimizing reaction parameters to improve enantioselectivity in the same palladium-catalyzed allenoic acid-forming reaction.
Abdur-Rashid et al. teaches that Garphos-type biaryl diphosphine ligands are useful in transition metal catalysts for asymmetric synthesis, including palladium-catalyzed reactions, kinetic resolution, dynamic kinetic resolution and carbonylation.
Strem Chemicals confirms that (R)-BTFM-Garphos was a known Garphos ligand available before the effective filing date.
Thus, at the time of the instant invention, one of ordinary skill in the art would have been motivated to substitute one known chiral bisphosphine ligand for another known chiral biaryl diphosphine ligand in Zheng et al.’s asymmetric palladium catalytic system with a reasonable expectation of success.
Furthermore, Zheng et al. already teaches the claimed reaction components and conditions, including tertiary propargyl alcohol, palladium catalyst, chiral bisphosphine ligand, organophosphoric acid/Brønsted acid, PPh3 supporting ligand, organic solvent, carbon monoxide and water. Zheng et al. teaches that the reaction proceeds in toluene under CO and water to form tetrasubstituted chiral 2,3-allenoic acids in high enantioselectivity.
The claimed palladium catalysts, organophosphoric acids, organic additives, solvents, ratios and temperatures would have been obvious optimizable parameters, especially since Zheng et al. teaches optimization of chiral ligand, supporting ligand, Brønsted acid, water amount, solvent, temperature, palladium catalyst and reaction parameters in the same reaction system.
With regard to claim 3, Zheng et al. teaches carrying out the reaction using a palladium catalyst, chiral ligand, Brønsted acid, water, CO and solvent to prepare the allenoic acid product, and the specific order of addition, use of argon, carbon monoxide balloon, low temperature bath, filtration and chromatographic purification would have been obvious routine laboratory procedures for carrying out and purifying the same palladium-catalyzed carbonylation/carboxylation reaction.
With regard to claim 4, Zheng et al. teaches palladium catalysts for the reaction, including [Pd(π-allyl)Cl]2 and PdCl2, which read on or render obvious the claimed palladium catalysts.
With regard to claims 5 and 6, Abdur-Rashid et al. and Strem Chemicals teach the Garphos/BTFM-Garphos family of chiral biaryl diphosphine ligands, including the elected BTFM-Garphos-type ligand.
With regard to claim 7, Zheng et al. teaches using (PhO)2POOH as the Brønsted acid/organophosphoric acid and teaches that (PhO)2POOH was most efficient in activating the hydroxyl group.
With regard to claim 8, Zheng et al. teaches PPh3 as a supporting ligand/additive and toluene as a solvent, and further teaches that chlorobenzene performed similarly to toluene.
With regard to claim 9, the claimed ratios, temperature and solvent amount overlap with or would have been obvious optimizations from the reaction conditions taught by Zheng et al.
Note that an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). The similarity of the known chiral bisphosphine ligands, as ligands for asymmetric transition metal catalysis, suggests the ligands have similar properties and utilities and would have been expected to be useful in the same palladium-catalyzed asymmetric reaction system. The prior art provides the same effect desired by applicant, the utilization of chiral bisphosphine ligands in palladium catalytic systems for preparing optically active chiral products.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer Cho Sawyer whose telephone number is (571) 270 1690. The examiner can normally be reached on Monday-Friday 9 AM - 6 PM PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-274-1690.
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Jennifer Cho Sawyer
Patent Examiner
Art Unit: 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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