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 .
This is a second Non-Final Office Action.
Election/Restrictions
Applicant's election with traverse of Group (I) in the reply filed on December 12, 2025 is acknowledged. Group (I), drawn to a process for the synthesis of 21-(acetyloxy)-17-(1- oxopropoxy)-pregn-4-ene-3,20- dione (compound of formula (VI)), embraced by claims 15-22 was elected by Applicant.
Applicant elected the following for the species election: enzymatic hydrolysis with supported lipase as the enzyme, and continuous flow conditions. Claims 15, 16 and 18-22 read on the election.
Claims 15-27 are pending and claims 15, 16 and 18-22 are under examination. Claim 17 is withdrawn based on the species election. Claims 23-27 are withdrawn based on the lack of unity.
Specification
The objection to the disclosure because of the formulas on page 3 being blurry is withdrawn based on the amendments.
Claim Rejections - 35 USC § 112
The rejection of claim 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the term “(21-chloro/21-bromo)-17a-hydroxy-3-(1- pyrrolidinium-1-yliden)-pregn-4-en-20-one chloride” is withdrawn based on the amendments.
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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) 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 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 15, 16 and 18-22 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Claudel et al. ((Synthesis, 2009, 20, 3391-3398), cited on the IDS) in view of Swaminathan et al. (Tettrahedron, 1987, 13(16), 3827-3838), Ryakhovskaya et al. (Pharm Chem., 1990, 24, 839-842, cited on the IDS), Cosmo Spa (WO 2009019138, cited on the IDS), Mugo et al. (Journal of Molecular Catalysis B: Enzymatic, 2010, 67, 202-207) and Mei et al. (Process Biochemistry, 2020, 98, 241-246).
The present application the following process:
PNG
media_image1.png
366
697
media_image1.png
Greyscale
PNG
media_image2.png
469
646
media_image2.png
Greyscale
PNG
media_image3.png
336
660
media_image3.png
Greyscale
PNG
media_image4.png
250
546
media_image4.png
Greyscale
Followed by selected hydrolysis with a lipase of the beta position of the steroid as follows found in claims 16-22:
PNG
media_image5.png
218
567
media_image5.png
Greyscale
Claudel et al. teach instant steps a), b) and c) as shown below and page 3392:
PNG
media_image6.png
153
215
media_image6.png
Greyscale
PNG
media_image7.png
176
699
media_image7.png
Greyscale
PNG
media_image8.png
54
842
media_image8.png
Greyscale
Claudel does not teach the intermediate mixture (IV) as presently claimed. However, based on the reaction conditions in Claudel, the mixture of intermediate (IV) is inherently made.
Swaminathan teaches the conversion of compound 16 with HCl and Br2, see steps 11 and 12 below the reactions on page 3829, with a similar compound as presently claimed, to obtain the presently claimed mixture of chloro and bromo-intermediates (IV), similar to instant step d) above.
PNG
media_image9.png
232
616
media_image9.png
Greyscale
The only difference between the claimed compounds and the cited compound 16, is the methyl group at C-16 of the steroid core. Since a methyl group is considered a homologue of hudrogen these compounds are considered equivalent. These compounds are homologues. The MPEP 2144.09 states “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).
Moreover, similar compounds are expected to have similar properties, see MPEP 2144.09, “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990).”
Claudel et al. does not teach step e) of the present synthesis.
Ryakhovskaya et al. teaches step e) of the claimed synthesis with acetic anhydride in the presence of perchloric acid (HClO4), see page 840 and below, also page 841, paragraph 4 for the discussion.
PNG
media_image10.png
85
181
media_image10.png
Greyscale
PNG
media_image11.png
36
63
media_image11.png
Greyscale
PNG
media_image12.png
112
140
media_image12.png
Greyscale
The difference between the acetic anhydride and Applicant’s propionic anhydride is the length of the carbon chain. These compounds are homologues. The MPEP 2144.09 states “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).
Claudel nor Ryakhovskaya teach the selective hydrolysis of the ester at position 21 of the steroid core.
Cosmo Spa (‘138 publication) teaches the selective hydrolysis using Candida lipase at position 21 over position 17 of the steroid core, see the bottom of page 2, page 3 and page 5, which teaches toluene and butanol as solvents.
Cosmo Spa does not each the enzymatic hydrolysis as a supported lipase or the reaction in a flow reactor.
Mugo et al. teach immobilized lipases in microreactors for lipid transformations, see abstract and Mei et al. teach lipase-catalyzed hydrolysis reactions in a microchannel reactor, see abstract.
Thus, the claims are rendered obvious over Claudel et al. in view of Swaminathan et al., Ryakhovskaya et al., Cosmo Spa, Mugo et al. and Mei et al.
This is a new rejection with an additional reference.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 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, Jeffrey Murray can be reached on 571-272-9023. 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.
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
Prosecution Insights