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 the first action on the merits.
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. The traversal is on the ground(s) that the compound cited by the Examiner is clearly different than compound (VI), see below:
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. Applicant points to the one difference between the compounds which is circled. However, these compounds are homologues and are considered equivalent. Since a methyl group is considered a homolog of hydrogen these compounds are considered equivalent. 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).
Applicant further notes that the asymmetric diester is more difficult to produce than a symmetric diester. This is not persuasive since this a general statement, which is relative, depending on the starting materials. As a reminder, the claims in Group (II) are drawn to a compound in the restriction requirement. Furthermore, homologues are considered equivalent and rendered obvious without a secondary teaching.
Therefore, the lack of unity is maintained.
The requirement is still deemed proper and is therefore made FINAL.
Applicant elected the following for the species election: enzymatic hydrolysis with supported lipase as the enzyme, and continuous flow conditions. Applicant indicated claims 15 and 18-22 read on the election. However, claim 16 is drawn to the hydrolysis step that claims 18-22 depend from. Therefore, claim 16 will also be examined.
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 Claim 17 is withdrawn based on the species election. Claims 23-27 are withdrawn based on the lack of unity.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 disclosure is objected to because of the following informalities: the formulas on page 3 are blurry and require replacement. 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.
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.
Claim 15 is 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 pre-AIA the applicant regards as the invention.
With regards to claim 15, the term “(21-chloro/21-bromo)-17a-hydroxy-3-(1- pyrrolidinium-1-yliden)-pregn-4-en-20-one chloride” is vague because of the “/,” see section b) and c).
To overcome the rejection, the 21-chloro and 21-bromo compounds should be named separately.
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) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 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:
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Followed by selected hydrolysis with a lipase of the beta position of the steroid as follows found in claims 16-22:
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Claudel et al. teach instant steps a), b) and c) as shown below and page 3392:
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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.
Claudel further teaches the conversion of an iodo-compound 11 to the acetyloxy compound 12 with acetic acid, see below and page 3393, versus Applicant’s mixture of chloro and bromo-intermediates (IV) to obtain the same product, see instant step d) above.
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The iodo-, chloro- and bromo-compounds similar and 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.
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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 Ryakhovskaya et al., Cosmo Spa, Mugo et al. and Mei et al.
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.
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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.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624