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 .
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.
Election/Restrictions
Applicant’s election of Group I (claims 1-12) and election of species “ODDA-Paclitaxel as the compound as Formula 11” and “the compound of Formula 15, wherein R14 is allyl” in the reply filed on 05/25/2026, are acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction/election requirement, the election has been treated as an
election without traverse (MPEP § 818.01(a)).
The prior art search of the process of preparing the elected species ODDA-Paclitaxel from Paclitaxel and compound of Formula 15 (wherein R14 is allyl) retrieved prior art reference (see attached search notes). Thus, the Markush search will not be unnecessarily extended in this action, in line with Markush search practice.
The elected species read on claims 1-12.
Claims 13-17 are withdrawn from further consideration pursuant to 37 CFR
1.142(b) as being drawn to nonelected inventions of Groups II and III, there being no allowable generic or linking claims. Election was made without traverse in the reply filed on 5/25/2026.
Current Status of 18/695,504
This Office Action is responsive to the amended claims filed on 09/29/2025. Claims 1-2, 4 are original. Claims 3, 6, 8-12 are previously presented. Claims 5 and 7 are currently amended. Claims 13-17 have been withdrawn. Claims 1-12 are pending and have been examined on the merits.
Priority
This application is a 371 of PCT/IB2022/059286 filed 09/29/2022, which claims the priority of ITALY 102021000025172 filed 09/30/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that the priority document is not in English. The effective filing date is 9/29/2022.
Information Disclosure Statement
The information disclosure statements (IDSs) filed on 3/26/2024 and 08/11/2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
15. Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
1). The claims lack written description because the instant claim 1 cites the limitation of R14 on Formula 15 (mono R14 protected octadecanedioic acid) as “R₁₄ is a protecting group that can be removed by catalysis with a transition metal”, which is described by function, and not by structure. There are no definitions in the Specification on what the protection groups are referred to. The artisan would not know what a protection group is used to perform the reaction.
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.
Claims 1-12 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
1). The claims are unclear because there are grainy chemical structures/formulas in claim 1 Formula (11) and claims 3, 6, 7 and 12. Many variables and alkyl chain numbers cited in the claims are difficult, and/or impossible, to discern. The artisan can’t describe them without knowing the variables. That make the claims indefinite.
2). The phrase “alternated with” is cited multiple times in claims 1 and 2 when the variables are defined, for example, in defining R1, R3, R4, R8 and R9 (see the screen shot below, highlighted in green). It occurs multiples times when defining R2, R6, R7, R10 and R11; R12 and R13. It’s not clear if they are replaced with or interposed. That make the claims indefinite.
3). The double bonds cited multiple times in claim 1 (between the arrows on the last line of the screen shot below) when the variables are defined, for example, in defining R1, R3, R4, R8 and R9. It occurs multiples times under R2, R6, R7, R10 and R11; R12 and R13 in claim 1. It’s not clear how these double valence bonds are connected to a single valence variables, such as R6 or R7 thereby rendering the claims indefinite.
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4). The open valence exists with some variables cited in claim 1(Between the arrows in the screen shot)) and claim 2. The compounds would be missing an attachment(s) to the opening end (such as -O-, -NH-, =N-, etc.), so we don't have fully defined compounds, rendering the claims indefinite.
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I 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.
19. Claim(s) 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over CALLMANN (US20180000951 A1, pub. 01/04/2018) in view of ALAOUI (Alaoui et al. “Protecting Groups for Glucuronic Acid: Application to the Synthesis of New Paclitaxel (Taxol) Derivatives” J. Org. Chem. 2006, 71, 9628-9636) and HUANG (Huang et al. “An Efficient Method for Removal of Residual Palladium from Organic Solution of Faropenem Sodium in the Pd(II)-Catalyzed Cleavage of Allyl Faropenem” Organic Process Research & Development 2010, 14, 939–941).
Determining the scope and contents of the prior art
CALLMANN teaches preparation of fatty acid attached taxanes, including mono-TIPS octadecanedioic-acid paclitaxel (ODDA-paclitaxel) for anticancer drugs. The preparation involves making a mono-TIPS protected octadecanedioic acid intermediate, then reacting the acid intermediate with a taxane, such as paclitaxel, and finally removing the TIPS protecting group with a conventional fluoride base at room temperature (see following schemes. Example 1, p 20).
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ALAOUI teaches allyl ester and allyl carbonates used as protecting groups of the glucuronic moiety linked to paclitaxel and their easy removal using Pd(PPh3)4 catalyst to afford the desired compounds in good yields without chromatographic purification (Conclusion).
HUANG teaches improved cleavage reactions of the allyl group in allyl faropenem using different palladium-catalysts, such as PdCl2(PPh3)2/PPh3, Pd(PPh3)4, Pd(OAc)2, and PdCl2 and an efficient method for the removal of palladium impurities from the crude product.
Ascertaining the differences between the prior art and the claims at issue
The claims are generally directed to a process for making high-purity anticancer drugs of taxane derivatives, especially octadecanedioic-acid paclitaxel (ODDA-paclitaxel). The process comprises making a mono-protected octadecanedioic acid intermediate, then coupling that acid to a taxane such as paclitaxel, followed by removing the protecting group with a transition-metal catalyst under mild conditions, instead of harsher deprotection methods. The process is designed to suppress dimeric or over-esterified impurities during synthesis. The result is a product in higher purity and, for ODDA-paclitaxel, in a more manageable solid form. Overall, the invention is focused on making taxane prodrugs cleaner, more scalable, and easier to isolate.
CALLMANN’s teaching meets all limitations of claim 1, except: 1). mono-TIPS protected ODDA in the reference vs. mono-allyl protected ODDA in claim 1; 2) removal of the protecting group with Bu4NF in reference vs. a transition metal catalyst (for example, a palladium catalyst).
ALAOUI teaches allyl ester and allyl carbonates used as protecting groups of the glucuronic moiety linked to paclitaxel and their easy removal using Pd(PPh3)4 catalyst to afford the desired compounds in good yields without chromatographic purification.
ALAOUI cures both CALLMANN’s defects of allyl protection of an acid moiety linked to paclitaxel and removing the allyl protecting group using a palladium catalyst.
HUANG further teaches expanding scope of palladium catalysts for improved cleavage reactions of the allyl group and provides an efficient method for the removal of palladium impurities from the crude product to meet the requirement on limit of metals (for example, below 10 ppm for Pd) in API products (see Introduction).
Considering objective evidence present in the application indicating obviousness or nonobviousness
Regarding the elected species “ODDA-Paclitaxel” and its preparation with mono-allyl protected ODDA, CALLMANN teaches its synthesis from paclitaxel and mono-TIPS protected ODDA as Example 2 ([0127]-[0128], p 20). Both processes are similar and the protecting groups of allyl and TIPS are commonly used in the art. It would have been obvious for an artisan before the effective filing date of the claimed invention to modify the mono-TIPS protected ODDA of CALLMANN with allyl protecting group as taught by ALAOUI with a reasonable confidence of success as demonstrated by ALAOUI. The reason for the modification is that its easy introduction and mild conditions of removal with palladium taught by ALAOUI (the last paragraph, p 9629).
Thus, Claims 1-7 are obvious over CALLMANN in view of ALAOUI.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over CALLMANN in view of ALAOUI of claims 1-7 above further in view of HUANG.
Claim 8 is drawn to more transition metal catalysts, Huang discloses improved cleavage reactions of the allyl group using different palladium-catalysts, such as PdCl2(PPh3)2/PPh3, Pd(PPh3)4, Pd(OAc)2, and PdCl2 thereby making claim 8 obvious.
Regarding claims 9 and 10 drawn to separation and purification of product, such as extraction and crystallization, CALLMANN discloses the Paclitaxel-C18 diacid conjugate (PTX-FA18) coming out through precipitation and extraction without chromatography after deprotection of the TIPS group ([0128], p.20). In addition, ALAOUI teaches removal of allyl protecting group using Pd(PPh3)4 catalyst to afford the desired compounds in good yields without chromatographic purification. Although CALLMANN and ALAOUI do not expressly disclose the solvents used to wash/purify the product, the artisan would know it as a routine optimization and of general knowledge of the art.
Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA1969). For more recent cases applying this principle, see in re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); In re Williams, 36F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Regarding claims 11 and 12, directing to the contents of impurities/purity of product, ALAOUI teaches that the conditions for removal of allyl protecting group with Pd(PPh3)4 in the presence of Et3N/HCO2H avoid the formation of byproducts during the classical deprotection (the last paragraph, p. 9631). A process of avoiding the formation of byproduct would increase the yield of product with less amounts of impurities.
Therefore, claims 9-12 are obvious over CALLMANN in view of ALAOUI.
Conclusion
Claims 1-12 are rejected.
Claims 13-17 are withdrawn.
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/B.T./
Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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