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 1-11 of A. Padilla-Acevedo et al., US 18/289,307 (Jun. 1, 2022) are pending and under examination. Claims 1-11 are rejected.
Maintained 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under AIA 35 U.S.C. 103(a) 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 1-11 are rejected under AIA 35 U.S.C. 103 as being unpatentable over A. Padilla-Acevedo et al., WO 2019/067272 (2019) (“Padilla-Acevedo”) in view of K. Jantunen et al., Journal of Alloys and Compounds, 363-368 (2007) (“Jantunen”); N. G. Anderson, PRACTICAL PROCESS & RESEARCH DEVELOPMENT, 27-52 (2000) (“Anderson”); and Y. Hayashi, 7 Chemical Science, 866-880 (2016) (“Hayashi”).
A. Padilla-Acevedo et al., WO 2019/067272 (2019) (“Padilla-Acevedo”)
Padilla-Acevedo teaches that metallocene complexes comprise a transition metal atom that is bonded to two ligands independently selected from an unsubstituted cyclopentadienyl (Gp) ligand (formally an anion of formula C5H5) and/or a substituted cyclopentadienyl ligand, which is isolobal to Gp and the transition metal is an element of any one of Groups 3 to 12 (such as titanium, zirconium, and hafnium) are useful for catalyzing polymerizations of olefins. Padilla-Acevedo at page 1, [0002].
Padilla-Acevedo teaches a method prepare a zirconocene dimethyl complex, the method comprising synthesizing the compound (8) and/or its R5/R4 regioisomer and contacting the compound (8) and/or its R5/R4 regioisomer with an effective amount of methyl magnesium bromide under reaction conditions sufficient to make a compound of formula (9). Padilla-Acevedo at page 7, [0014].
Padilla-Acevedo teaches working Example 13, summarized by the Examiner as follows, where correspondence to instant claim 1 is indicated in parentheticals.
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Padilla-Acevedo at pages 25-26, [0084].
Padilla-Acevedo, Example 13, meets each and every limitation of the claim 1 step of:
Claim 1 . . . reacting a chloride compound with a lithium compound to make a reaction mixture comprising an intermediate dichloride compound . . .
Padilla-Acevedo further teaches prophetic example 7, summarized by the Examiner as follows, where correspondence to instant claim 1 is indicated in parentheticals.
PNG
media_image2.png
200
400
media_image2.png
Greyscale
Padilla-Acevedo at page 23, [0078]. Padilla-Acevedo, Example 7, meets each and every limitation of the claim 1 step of
Claim 1 . . reacting the intermediate dichloride compound with an alkylating agent to make the alkylated metallocene having one or more tetrahydropentalenyl groups . . .
Differences between Padilla-Acevedo and Claim 1
Padilla-Acevedo differs from instant claim 1 in that it does not teach the following claim 1 limitations:
Claim 1 . . . wherein the dichloride compound is not isolated from the reaction mixture . . .
wherein the reactions occur in the same reaction vessel.
Rather, Padilla-Acevedo first isolates the (intermediate) dichloride compound and then reacts it with methyl magnesium bromide (the claim 1 alkylating agent).
K. Jantunen et al., Journal of Alloys and Compounds, 363-368 (2007) (“Jantunen”)
Jantunen is cited here as evidencing the facile and high-yield nature of displacement of dichloride from zirconium and hafnium cyclopentadienyl metallocenes with methyl magnesium bromide to give the demethylated compound.
Jantunen teaches preparation of (C5H5)2Zr(CH3)2 (1) by reacting (C5H5)2Zr(Cl)2 (12) with magnesium bromide in diethyl ether at room temperature, following by precipitating the product with dioxane, to give the corresponding dimethyl product (1) in 94% yield, summarized by the Examiner as follows:
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Jantunen at page 366, col. 1. Jantunen teaches the same result with the corresponding hafnium metallocene. Id.
N. G. Anderson, PRACTICAL PROCESS & RESEARCH DEVELOPMENT, 27-52 (2000) (“Anderson”)
Anderson teaches that chemists have developed generally applicable paradigms for synthetic-process optimization; for example, use of convergent synthesis, telescopic workups, solvent and protecting group selection, and minimizing the number of reaction steps. Anderson at pages 27-52. Anderson teaches that telescopic workup can be cost effective. See Anderson at page 29, Table 2.1. In this regard, Anderson teaches that isolating intermediates has many potential disadvantages; for example, isolation is usually costly and invariably leads to some loss of valuable material and that on a manufacturing scale, isolating intermediates and API requires about 50% of personnel time and about 75% of equipment financial outlay and that this additional handling required increases both exposure of operators to pharmacologically potent materials and opportunities for contamination of batches and loss of valuable product. Anderson at page 34. Anderson teaches that isolations are avoided by telescoping, also known as concatenation or through-processes, is the process of carrying the product of a reaction without isolation into the next step and that appropriate telescoping can greatly increase overall yields. Anderson at page 34. Anderson further teaches that unless significant purification or other benefits are realized by isolating intermediates, telescoping is incorporated as part of cost-effective routes. Anderson at page 34.
Y. Hayashi, 7 Chemical Science, 866-880 (2016) (“Hayashi”)
Hayashi teaches that the one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry. Hayashi at Abstract. Hayashi teaches that “telescoped”, “one pot” reactions, where intermediates are not isolated improve reaction economy (reduces expense) because intermediate workups are avoided. Hayashi at page 868, col. 1 (4). Hayashi discusses criteria for effective one-pot synthesis of, including the case where the intermediate compound is unstable or hazardous. Hayashi at page 868, col. 2 (6.1).
Obviousness Rationale
One of ordinary skill is motivated to obtain the following dimethyl zirconium metallocene (falling with the scope of claim 1):
PNG
media_image4.png
200
400
media_image4.png
Greyscale
in view of Padilla-Acevedo’s teaching that such metallocenes are useful catalysts in olefin polymerization. Padilla-Acevedo at page 1, [0002].
One of ordinary skill is motivated to practice Padilla-Acevedo Example 13 and then treat the reaction solution of dichloro-intermediate 9-1 directly (without isolation as taught by Padilla-Acevedo), in the same reaction vessel, with two equivalents of methyl magnesium bromide to give the desired dimethyl product directly in a one-pot procedure. One of ordinary skill is so motivated in view of Anderson’s and Hayashi’s teachings that a one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry. One of ordinary skill thereby meets every limitation of claim 1, including the claim 1 limitations of:
Claim 1 . . . wherein the dichloride compound is not isolated from the reaction mixture . . .
wherein the reactions occur in the same reaction vessel.
One of ordinary skill has a reasonable expectation of success because Jantunen evidences the facile and high-yield nature of displacement of dichloride from zirconium cyclopentadienyl metallocenes with methyl magnesium bromide to give the demethylated compound. Claim 1 is therefore obvious.
The limitations of claims 2-6 are clearly met by practice of Padilla-Acevedo as proposed above.
Claim 7 is clearly claimed using ‘product by process language’:
Claim 7 . . . wherein the lithium compound is made by. . .
Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. MPEP § 2113(I). If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. MPEP § 2113(I) (citing In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)).1 The Padilla-Acevedo lithium compound 6-1 is the same lithium compound claimed, therefore the further claim 7 product-by-process limitations, regarding its source, cannot distinguish over the cited art. MPEP § 2113(I).
Claim 7 is obvious under the following alternative rational, Padilla-Acevedo teaches that lithium compound 6 is prepared by contacting compound 5 with an alkyl lithium under reaction conditions sufficient to make compound 6, summarized by the Examiner as follows:
PNG
media_image5.png
200
400
media_image5.png
Greyscale
Padilla-Acevedo at page 5, [0013].
In working Example 5, Padilla-Acevedo demonstrates the synthesis of compound (6-1), where R1 to R3 are H and R4 and R5 are methyl, by treating the corresponding compound 5 with butyl lithium in hexanes (38% yield). Padilla-Acevedo at page 22, [0076]. Padilla-Acevedo therefore teaches even the product-by-process limitations of claim 7. Claim 7 is obvious because one of ordinary skill is motivated to prepare the lithium compound 6-1 according to Padilla-Acevedo (as discussed above) for use in the above-proposed modification of Padilla-Acevedo Example 13.
Claim 8 is clearly claimed using ‘product by process language’:
Claim 8 . . . wherein the bicyclic alkene compound is made by reacting a bicyclic ketone compound with an alkylating agent and diethyl ether to form a bicyclic alcohol compound and dehydrating the bicyclic alcohol compound to make the bicyclic alkene compound. . .
The claim 8 product-by-process language does not distinguish over Padilla-Acevedo for the same reasons as claim 7 above.
In any case, claim 8 is obvious under the following alternative rational. Respecting instant claim 8, Padilla-Acevedo teaches the compound 5 is prepared by contacting compound 3 with either a hydride-functional reducing agent or a (C1-C4)alkyl lithium to make compound 4 and then reacting compound 4 under dehydration reaction conditions to make a compound of formula (5), summarized by the Examiner as follows:
PNG
media_image6.png
200
400
media_image6.png
Greyscale
Padilla-Acevedo at page 4, [0012]. In working Example 3, Padilla-Acevedo demonstrates the synthesis of compound 4-1 (wherein R1 to R3 is H and R4 and R5 are methyl) by treating compound 3-1 with methyl lithium. Padilla-Acevedo at page 22, [0074]. In working Example 4, Padilla-Acevedo demonstrates the synthesis of compound 5-1 (wherein R1 to R3 is H and R4 and R5 are methyl) by hydrolyzing compound 4-1 with 6 M HCl. Padilla-Acevedo at page 22, [0075]. Padilla-Acevedo therefore teaches even the product-by-process limitations of claim 8. Claim 8 is obvious because one of ordinary skill is motivated to prepare the bicyclic alkene compound according to Padilla-Acevedo (as discussed above) for use in the above-proposed modification of Padilla-Acevedo Example 13.
Claim 9 is clearly claimed using ‘product by process language’:
Claim 9 . . . wherein the bicyclic ketone compound is made by reacting. . .
The claim 9 product-by-process language does not distinguish over Padilla-Acevedo for the same reasons as claim 7 above.
In any case, claim 9 is obvious under the following alternative rational. Respecting instant claim 9, Padilla-Acevedo teaches that compound 3 is prepared by contacting compound 1 with compound 2 in the presence of an effective amount of a phosphoric and/or sulfonic acid reagent, summarized by the Examiner as follows:
PNG
media_image7.png
200
400
media_image7.png
Greyscale
Padilla-Acevedo at page 3, [0011]. In working Example 2, Padilla-Acevedo demonstrates the synthesis of compound (3-1), where R1 to R3 are H, by reacting cyclopentene (compound 1) with (E)-2-butenoic acid (compound (2) wherein R4 is methyl) in the presence of polyphosphoric acid (PPA) (24% yield). Padilla-Acevedo at pages 21-22, [0073]. Padilla-Acevedo therefore teaches even the product-by-process limitations of claim 9. Claim 9 is obvious because one of ordinary skill is motivated to prepare the bicyclic ketone compound according to Padilla-Acevedo (as discussed above) for use in the above-proposed modification of Padilla-Acevedo Example 13.
The further limitations of claims 10 and 11, which are also all directed to product-by-process limitations, cannot distinguish over the cited art for the same reasons discussed above. In any case, claims 10 and 11 are obvious under the following alternative rational. Padilla-Acevedo teaches that in reaction of compound 1 with compound 2 to give compound 3, a P2O5/H3CSO3H mixture and a polar aprotic solvent may be employed. Padilla-Acevedo at page 15, [0058]. Padilla-Acevedo teaches that the polar aprotic solvent may be selected from sulfolane, 1,2-dimethoxyethane, 1-methoxy-2-(2-methoxyethoxy)ethane (known in the art as diglyme), and mixtures of any two or more thereof. Id. The specification also teaches that the aprotic solvent may be selected from sulfolane, 1,2-dimethoxyethane, diethylene glycol dimethyl ether (diglyme). Specification at page 10, [0038]. These solvents all have polarities falling within the claim 9 range. C. Reichardt, et al., Solvents and solvent effects in organic chemistry, 455-461 (4th ed. John Wiley & Sons, 2011). Claims 10 and 11 are obvious because one of ordinary skill is motivated to select any of sulfolane, 1,2-dimethoxyethane, 1-methoxy-2-(2-methoxyethoxy)ethane (known in the art as diglyme) as the solvent in base claim 9 to prepare the bicyclic ketone compound (3) and also use a P2O5/H3CSO3H mixture because these are the solvents and reagents specifically taught by Padilla-Acevedo.
Applicant’s Argument
Applicant argues that Padilla-Acevedo neither teaches nor suggests improving the alkylation process itself by performing the metalation reaction and the subsequent alkylation reaction as a one-pot synthesis without isolating the intermediate dichloride compound. Reply at page 6. Applicant argues that Padilla-Acevedo provides no teaching or suggestion to eliminate these isolation and purification operations and instead directly introduce the alkylating agent into the reaction mixture in a same reaction vessel; rather, doing so would require modification of the synthetic sequence expressly utilized by Padilla-Acevedo by eliminating the work-up and purification operations employed to obtain the isolated dichloride intermediate before subsequent alkylation. Reply at lines bridging pages 6-7. Applicant further argues to the effect that the additionally cited secondary references Anderson and Hayashi do not cure the argued deficiencies because these references are directed to structurally and conceptually different reactions and/or simply provide general teachings. Reply at pages 7-8.
These arguments are not considered persuasive for the following reasons. One of ordinary skill seeking the above-cited dimethyl zirconium metallocene (falling with the scope of claim 1) for use as a catalyst is motivated to develop optimal/efficient method for its synthesis. References Anderson and Hayashi teach the concept that one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry, including convergent synthesis, telescopic workups, and minimizing the number of reaction steps. Hayashi at Abstract; Anderson at pages 27-52. A "motivation to combine may be found explicitly or implicitly in market forces; design incentives; the ‘interrelated teachings of multiple patents’; ‘any need or problem known in the field of endeavor at the time of invention and addressed by the patent’; and the background knowledge, creativity, and common sense of the person of ordinary skill". MPEP § 2143.01 (citing Zup v. Nash Mfg., 896 F.3d 1365, 1371, 127 USPQ2d 1423, 1427 (Fed. Cir. 2018)). Padilla-Acevedo is clearly combinable with Anderson and/or Hayashi. Contrary to Applicant’s argument (Reply at page 8, last paragraph) the proposed reference combination clearly and directly produces the following claim 1 elements:
Claim 1 . . . wherein the dichloride compound is not isolated from the reaction mixture . . .
wherein the reactions occur in the same reaction vessel.
Applicant argues that there is not motivation to combine the cited references because Anderson and Hayashi are directed to structurally and conceptually different reactions and/or simply provide general teachings as well as the fact that these references point out that optimal routes require appreciable time to develop (Anderson) and careful selection of compatible reagents, reaction sequences, and reaction conditions, and further recognizes that there are a number of restrictions on one-pot reactions (Hayashi). However, one or ordinary skill is not deterred simply because the details have not been completely sorted.
Non-Statutory Double Patenting Rejections
The non-statutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) 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 non-statutory 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).
Non-Statutory Double Patenting Rejection over A. Padilla-Acevedo et al., US 11,299,508 (2022)
Claims 1-9 and 11 are rejected on the ground of non-statutory double patenting as being unpatentable over conflicting claims 1-4 of A. Padilla-Acevedo et al., US 11,299,508 (2022) in further view of in view of K. Jantunen et al., Journal of Alloys and Compounds, 363-368 (2007) (“Jantunen”); N. G. Anderson, PRACTICAL PROCESS & RESEARCH DEVELOPMENT, 27-52 (2000) (“Anderson”); and Y. Hayashi, 7 Chemical Science, 866-880 (2016) (“Hayashi”)
Conflicting claims 3 and 4 teach the limitations of conflicting claims 1-7, except the instant claim 1 limitation of:
Claim 1 . . . wherein the dichloride compound is not isolated from the reaction mixture . . .
is not stated. Instant claim 1 is obvious because one of ordinary skill is motivated to practice conflicting claim 3 and thereafter treat the reaction solution of dichloro-intermediate of conflicting claim 3 directly (without isolation as taught by Padilla-Acevedo) with two equivalents of methyl magnesium bromide (per conflicting claim 4) to give the desired dimethyl product directly. One of ordinary skill is so motivated in view of Anderson’s and Hayashi’s teachings that a one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry.
One of ordinary skill thereby meets the claim 1 limitations of:
Claim 1 . . . wherein the dichloride compound is not isolated from the reaction mixture . . .
wherein the reactions occur in the same reaction vessel.
and arrives at every limitation of claim 1. One of ordinary skill has a reasonable expectation of success because Jantunen evidences the facile and high-yield nature of displacement of dichloride from zirconium cyclopentadienyl metallocenes with methyl magnesium bromide to give the demethylated compound. Instant claims 1-7 are therefore obvious over conflicting claims 3 and 4 in view of the cited secondary art. The rationale is the same as discussed above for the § 103 rejection.
Conflicting claims 1, 2 and 7 teach the further limitations of instant product-by-process claims 8, 9 and 11.
Terminal Disclaimer
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 non-statutory 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 non-statutory 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.
Applicant’s Argument
Applicant argues that it submits a terminal disclaimer concurrently herewith to address the non-statutory double patenting rejection.
This argument is not persuasive because no terminal disclaimer has been filed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER R PAGANO whose telephone number is (571)270-3764. The examiner can normally be reached 8:00 AM through 5:00 PM.
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, Scarlett Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ALEXANDER R. PAGANO
Examiner
Art Unit 1692
/ALEXANDER R PAGANO/Primary Examiner, Art Unit 1692
1 Here, the product-by-process limitation is nested within a method claim; however, this does not change the analysis. Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334 (Fed. Cir. 2020) (“[t]he nesting of the product-by-process limitation within a method . . . claim does not change the proper construction of the product-by-process limitation itself . . . [a]n old method of administration of an old product made by a new process is not novel and cannot be patented”); see also non-binding, non-precedential board opinions in Ex parte Wohaibi, Appeal No. 2024-004112, 17/750,212 (PTAB 2025) and Ex parte Yang, Appeal No. 2025-000566, 17/587,166 (PTAB 2025) discussing and applying Biogen MA Inc. v. EMD Serono, Inc..
Prosecution Insights