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 .
Claim Objections
Claims 2-4 are objected to because of the following informalities: “characterized in that” should read “wherein”. 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.
Claims 1-4 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.
Claim 1 recites the limitation "the betulin solution" in line 3. There is insufficient antecedent basis for this limitation in the claim because the betulin solution is not recited previously in the claim and it is unclear what the betulin solution entails as it is not clearly defined.
Claim 4 recites the limitation "the diafiltration buffer solution" in line 2. There is insufficient antecedent basis for this limitation in the claim because the diafiltration buffer us not recited previously in the claim or the claim 1 or 2 for which claim 4 is dependent on and it is unclear what the diafiltration buffer entails as it is not clearly defined.
For the purposes of compact prosecution, “the betulin solution” is being understood as any solution that primarily contains betulin. It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection and art may be readily applied in a subsequent final Office action.
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.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov, et al. (RU 2545714 C1, FOR-IDS, filed 06/29/2023, hereinafter “Krasilnikov”) and further in view of O’Driscoll (Why Variable-Frequency Ultrasonic Homogenizers Don’t Exist, Laboratory Supply Network, 20 April 2019), FDA (Vaccine Excipient Summary January 2019), and Peng, et al. (Advanced Materials Volume 32, Issue 40 October 8, 2020, hereinafter “Peng”).
Regarding claim 1, Krasilnikov teaches a method of producing a betulin-based adjuvant for use in a viral vaccine comprising the following steps: (1) sterilizing a mixture of betulin and tetrahydrofuran (THF) by filtering through a nylon membrane with a pore size of 0.22 µm (Example 1 ¶1), (2) adding 25 volume of 0.01 M Tris buffer using a peristaltic pump and 15 minutes of constant stirring with a propeller-style stirrer (Example 1 ¶2), (3) ultrasonic homogenization for 5-10 minutes, creating spherical amorphous nanoparticles (Claim 1), and (4) removing THF through ultrafiltration (Claim 1).
Krasilnikov does not teach that ultrasonic homogenization occurs at 35 kHz. However, O’Driscoll teaches that the most common frequencies for ultrasonic homogenization are between 20-40 kHz (Frequency in Practice). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Krasilnikov of a method of producing a betulin-based adjuvant which includes ultrasonic homogenization with the teachings of O’Driscoll of the typical range of kHz (20-45) used for ultrasonic homogenization. One of ordinary skill would have a reasonable expectation of success with using a frequency within the range of the common prior art.
Krasilnikov and O’Driscoll do not teach that the adjuvant can be used for a SARS-CoV-2 vaccine. However, FDA teaches that a single adjuvant can be used in multiple viral vaccine (alum) and Peng teaches that alum can be used for SARS-CoV-2 vaccines. As the instant specification teaches that the betulin adjuvant can be used for both influenza and hepatitis B vaccines, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to use the betulin adjuvant in a SARS-CoV-2 vaccine.
Regarding claim 2, Krasilnikov teaches that the ultrafiltration occurs with a buffer solution and filter weight a molecular weight cut-off of 300 kDa (Abstract).
Regarding claim 3, Krasilnikov teaches that sonication causes homogenization (Example 1 ¶2). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to repeat the homogenization step taught by Krasilnikov after ultrafiltration in order to obtain the same and predictable benefit of a homogenized suspension.
Accordingly, the claimed method was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov, O’Driscoll, FDA, and Peng as applied to claims 1-3 above, and further in view of Gao, et al. (Journal of Membrane Science, Volume 587, 1 October 2019, 117136, hereinafter “Gao”).
As discussed above, claims 1-3 were rendered prima facie obvious by teachings of Krasilnikov, O’Driscoll, FDA, and Peng.
Regarding claim 4, Krasilnikov, O’Driscoll, FDA, and Peng teach that sonication at 35kHz causes homogenization. The references do not teach reversing the flow of the filter to remove particles.
However, Gao teaches that reversing the flow on during ultrafiltration will defoul the membrane, removing particles from the membrane and allowing for continuous flow and removing debris from the filter (Abstract). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Krasilnikov, O’Driscoll, FDA, and Peng for the method of sterilizing and filtering betulin and Gao of reversing the flow during ultrafiltration. Gao provided motivation by teaching that reversing the flow removing particles and mitigates membrane fouling (Abstract). One of skill in the art would have had reasonable expectation of success applying a known technique in the art of filtration to yield a predictable result of removing particles from the filter.
Accordingly, the claimed method was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672