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 Office action is responsive to Applicant’s amendment and remarks, filed 01 May 2026, in which claims 1, 11, and 21 are amended to change the scope and breadth of the claim, and claims 9, 19, and 29 are canceled.
This application is a domestic application, filed 05 Jan 2023; claims benefit as a CON of PCT/EP2021/068832, filed 07 July 2021; and claims benefit of foreign priority document EP 20184839.7, filed 09 July 2020. This foreign priority document is in English.
Claims 1-2, 4-8, 11, 18, 20-22, 24-25, 27-28, and 30 are pending in the current application. Claims 22 and 24-25, drawn to non-elected inventions, are withdrawn. Claims 1-2, 4-8, 11, 18, 20-21, 27-28, and 30 are examined on the merits herein.
Objections Withdrawn
Applicant’s amendment, filed 01 May 2026, with respect that the disclosure is objected to because it contains an embedded hyperlink has been fully considered and is persuasive, as the amended specification does not contain browser-executable code.
This objection has been withdrawn.
Rejections Withdrawn
Applicant’s amendment, filed 01 May 2026, with respect that claims 19 and 21 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been fully considered and is persuasive, as claim 19 is canceled, and amended claim 21 does not recite the indicated language.
This rejection has been withdrawn.
Applicant’s amendment, filed 01 May 2026, with respect that claims 1-2, 4-9, 11, 18, 20-21, and 27-30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by McPherson et al. (US 2022/0251128, filed 15 May 2020, of record) has been fully considered and is persuasive, as amended claim 1 recites the method further wherein the concentration of the iodine in the oxidation solution is 75 mM to 100 mM. Upon reconsideration, McPherson et al. does not specifically disclose a method meeting the all limitations of the claimed invention.
This rejection has been withdrawn.
Applicant’s amendment, filed 01 May 2026, with respect that claims 1-2, 4-8, 18, 20-21, 27-28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Reddy et al. (US 5,783,684, issued 21 July 1998, provided by Applicant in IDS filed 03 Dec 2024) in view of Zon (Argrawal, S., ed., Methods in Molecular Biology, Vol. 20 Protocols for Oligonucleotides and Analogs, 1993, Humana Press Inc., p165-189, of record) has been fully considered and is persuasive, as amended claim 1 recites the method further wherein the concentration of the iodine in the oxidation solution is 75 mM to 100 mM. Upon reconsideration, Reddy et al. in view of Zon does not teach or fairly suggest a method meeting the all limitations of the claimed invention.
This rejection has been withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment, filed 01 May 2026, in which claims 1, 11, and 21 are amended to change the scope and breadth of the claim, and claims 9, 19, and 29 are canceled.
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 (i.e., changing from AIA to pre-AIA ) 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, 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.
Amended Claims 1-2, 4-8, 11, 18, 20-21, 27-28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over McPherson et al. (US 2022/0251128, filed 15 May 2020, of record).
McPherson et al. discloses methods for synthesizing oligonucleotides having at least one phosphorothioate diester linkage and at least one phosphate diester internucleoside linkage. In certain embodiments, the present disclosure provides oxidation reagents that produce low amounts of unwanted phosphate diester impurities (abstract). The oxidation step comprises oxidation of an intermediary phosphite triester compound into a phosphodiester compound (figure 2, step 3), addressing the structural limitations of the claimed formulas I and II. The oxidizing agent can be used to produce highly pure oligonucleotides that contain only a low percentage of unwanted phosphate diester linkages. In certain embodiments, adding an iodide source to a pyridine, water, and iodine oxidizing reagent results in an oxidizing reagent that can be used promptly upon preparation (paragraph 11 spanning pages 1-2), addressing limitations of claim 1 and 6-7. In certain embodiments, the oxidizing agent is a mixture of I2, a salt, pyridine, and water. In certain embodiments, the salt is selected from Nal, KI, Lil, or pyridinium iodide. In certain embodiments, the concentration of I2 is 0.001 M, 0.08 M, 0.09 M, or 0.1 M, or any range selected from two values above. In certain embodiments, the concentration of the salt is the same as the concentration of I2. In certain embodiments, the concentration of the salt is 0.001 M, 0.08 M, 0.09 M, or 0.1 M. In certain embodiments the oxidizing agent is a mixture of 0.05 M I2, 0.05 M KI, in a 9:1 volumetric ratio of pyridine and water (page 10, paragraph 234-235), addressing limitations of claims 1-2, 4-9, and 27-28. In working example 11, the oligonucleotide compound 682884 precursor is synthesized using the freshly prepared oxidizing agent to give a (P=O)1 impurity of 1.7% and no detectable incomplete oxidation (page 25, paragraph 362 to page 26, paragraph 363), addressing limitations of claims 18 and 30. The oligonucleotide compound 682884 contains 20 nucleotides (page 23, paragraph 338), addressing limitations of claim 21.
McPherson et al. does not specifically disclose the method wherein the concentration of the iodine in the oxidation solution is 75 mM to 100 mM (claim 1). McPherson et al. does not specifically disclose the method wherein the oxidation solution comprises 100 mM KI and 100 mM I2, and the oxidation solution has a conductivity of between 3200 and 3900 μS/cm (claim 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of McPherson et al. to select the concentration of the I2 and the salt in the oxidizing agent. One of ordinary skill in the art would have been motivated to select the concentration of the I2 and the salt in the oxidizing agent with a reasonable expectation of success because McPherson et al. teaches in certain embodiments the concentration of I2 is 0.08 M, 0.09 M, or 0.1 M, and in certain embodiments, the concentration of the salt is the same as the concentration of I2, and teaches embodiments where the oxidizing agent is a mixture of I2 and KI at the same concentration in a 9:1 volumetric ratio of pyridine and water, suggesting it would have been obvious to select the concentration to be 0.1 M (or 100 mM) I2 and 0.1 M KI in a 9:1 volumetric ratio of pyridine and water.
Regarding claim 11, McPherson et al. is silent as to the conductivity of the oxidation solution. MPEP 2112.01 especially at I. citing In re Best, 562 F.2d 1252, 195 USPQ 430 (C.C.P.A. 1977) and In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly recited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to show the inventions of the applicant and the prior art are not the same or that the prior art inventions do not necessarily possess the characteristics of the claimed invention. Further, MPEP 2112 provides “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) In this case McPherson et al. discloses embodiments and working examples of the oxidizing agent being a mixture of 0.05 M I2, 0.05 M KI, in a 9:1 volumetric ratio of pyridine and water, and provides guidance for selecting the concentration of I2 is 0.1M (or 100 mM) and the concentration of the salt is the same as the concentration of I2, making obvious the oxidizing agent have the same components and concentrations as the oxidation solution of the claimed invention. The conductivity of the oxidation solution would be a resultant physical property of the specific solvents, solutes in the solution, and their concentrations.
Regarding claim 20, McPherson et al. does not explicitly disclose the reaction temperature of the oxidation reaction. However, McPherson et al. discloses the invention as an improvement in the field of current solid-phase synthesis manufacturing processes of phosphorothioate diester linked oligonucleotides (page 1, paragraphs 4-7). One of skill in the art would have understood that in the state of the art at the time of McPherson et al. this step of the process is performed at room temperature, addressing limitations of claim 20. Further, McPherson et al. describing the manufacturing processes at page 1, paragraph 9 does not specify heating or cooling for the reaction steps, suggesting that the reactions are performed at room temperature and making obvious this limitation of claim 20.
Response to Applicant’s Remarks:
Applicant’s Remarks, filed 01 May 2026, have been fully considered and not found to be persuasive.
As detailed in the new grounds of rejection above, the broader disclosure of McPherson et al. teaches in certain embodiments the concentration of I2 is 0.08 M, 0.09 M, or 0.1 M, and in certain embodiments, the concentration of the salt is the same as the concentration of I2, and teaches embodiments where the oxidizing agent is a mixture of I2 and KI at the same concentration in a 9:1 volumetric ratio of pyridine and water, suggesting it would have been to select the embodiment wherein the oxidizing agent is a mixture of I2 and KI at the same 0.1 M or 100 mM concentration in a 9:1 volumetric ratio of pyridine and water. The specification at page 11 appears to show similar results for this embodiment compared to the embodiment where the oxidizing agent is a mixture of 50 mM I2 and 50 mM KI, which is the closest disclosed prior art embodiment.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Jonathan S Lau whose telephone number is (571)270-3531. The examiner can normally be reached Monday-Friday 9a-5p Eastern.
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.
/JONATHAN S LAU/Primary Examiner, Art Unit 1693
Prosecution Insights