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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed on 29 June 2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Response to Amendment
The amendment filed 27 April 2026 in which claims 1-4 were amended and claims 5-6 were added has been entered.
Claims 1-6 are under examination on the merits.
Claim Objections
(Previous objection, withdrawn as to claims 2-4). Applicant’s amendments to claims 2-4 submitted on 27 April 2026 have overcome the objection previously set forth in the Non-Final Office Action mailed 26 January 2026.
(New objection). Claim 1 is objected to because of the following informalities: “SARS-COV2” in line 2 should read “SARS-CoV-2” Appropriate correction is required.
Claim Interpretation
Instant claim 1 is drawn to a “method of production of a betulin-based adjuvant for use in a SARS-COV-2 vaccine.” As such, the claim is drawn to a method of producing a betulin-based adjuvant with an intended downstream use of producing a SARS-CoV-2 vaccine with the betulin-based adjuvant. It is noted that only instant claim 5 actually requires “formulating the purified suspension with a SARS-CoV-2 antigen.”
As such, the intended use recited in instant claim 1, while fully considered, was not given any patentable weight, and the claim was broadly interpreted to read on any prior art method comprising the recited method steps, which, absent evidence to the contrary, would yield a betulin-based adjuvant suitable for the recited intended use.
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.
(Previous rejection, withdrawn as to claims 1-4). Claims 1-4 were 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. The rejection is withdrawn due to Applicant’s amendment to claims 1 and 4 submitted on 27 April 2026.
(new rejection). Claims 1-6 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.
Regarding claim 1, the phrase "(pH-9.0±0.1)" renders the claim indefinite because it is unclear whether the limitation(s) following in the parentheses are part of the claimed invention or an example. See MPEP § 2173.05(d).
Claim 1 recites the limitation "the SARS-CoV-2 protein" in line 12. There is insufficient antecedent basis for this limitation in the claim. There is insufficient antecedent basis for this limitation in the claim because the SARS-CoV-2 proteins are not recited previously in the claim.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Prior rejection, withdrawn as to claims 1-3). Claims 1-3 were rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov and further in view of O’Driscoll, FDA, and Peng.
(Prior rejection, withdrawn as to claim 4). Claim 4 was rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov, O’Driscoll, FDA, and Peng as applied to claim 1-3 above and further in view of Gao.
(new rejection). Claims 1-3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov and further in view of O’Driscoll.
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.
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.
Regarding claim 6, Krasilnikov teaches that the betulin solution before sterilization with a nylon membrane comprises betulin, THF, and oleic acid (Example 1 ¶1). Oleic acid is added to the solution to ensure storage stability (pg. 6 lines 18-24). Adding oleic acid to the solution does not change the predictable final product of a betulin solution, removing the oleic acid would only remove the function of ensuring storage stability. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention that the oleic acid taught by Krasilnikov was an optional component that is only required when the function of the oleic acid, storage stability, is desired. See MPEP 2144.04(II)A). The Specification does not demonstrate any unexpected results or characteristics that occurred by not adding in/removing the oleic acid from the betulin-based solution before purification.
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.
(new rejection). Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov and O’Driscoll as applied to claims 1-3 above, and further in view of Grimes, et al. (WO 9640733 A1, hereinafter “Grimes”).
As discussed above, claims 1-3 and 6 were rendered prima facie obvious by teachings of Krasilnikov and O’Driscoll.
Regarding claim 4, Krasilnikov and O’Driscoll teach that sonication at 35kHz causes homogenization. The references do not teach reversing the flow of the filter to remove particles.
However, Grimes teaches backflushing the ultrafiltration/diafiltration device (Figure 1, 13) to remove the particles from the membrane (Operation 4, pages 12 and 13).
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 and O’Driscoll for the method of sterilizing and filtering betulin and Grimes of backflushing after ultrafiltration/diafiltration. Grimes provides motivation by teaching that backflushing removes particles from the membrane (Operation 4 pgs 12 and 13). 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.
(new rejection). Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Krasilnikov and O’Driscoll.as applied to claims 1-3 and 6 above, and further in view of Taylor, et al. (https://www.labome.com/method/SARS-CoV-2.html, available at WayBack Machine https://web.archive.org/web/20201202100025/https://www.labome.com/method/SARS-CoV-2.html published 02 December 2020, hereinafter “Taylor”).
As discussed above, claims 1-3 and 6 were rendered prima facie obvious by teachings of Krasilnikov and O’Driscoll.
Regarding claim 5, Krasilnikov teaches that the betulin adjuvant can be used for a variety of viral vaccines to enhance the immunogenic activity of the viral vaccine (Effect). This includes viral protein vaccines like the surface antigens of the hepatitis B virus (Examples 4-5) and influenza hemagglutinin (Example 6). Krasilnikov and O’Driscoll do not teach a SARS-CoV-2 protein vaccine. However, Taylor teaches that the SARS-CoV-2 S protein is a major target for SARS-CoV-2 vaccines included protein-based vaccines (Vaccine Development, ¶1 and 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the viral protein antigens taught by Krasilnikov for the SARS-CoV-2 S protein taught by Taylor. Krasilnikov teaches that the betulin adjuvant can be used for many different vaccines including viral protein vaccines (Examples 4-6). One of skill in the art would have had a reasonable expectation of success in substituting the viral protein antigens taught by Krasilnikov for the SARS-CoV-2 S protein taught by Taylor because they are both immunogenic proteins used in vaccines.
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.
Response to Arguments
Applicant contends on pages 2-7 of the Remarks submitted on 27 April 2026 that Krasilnikov teaches adding oleic acid to the solution while the instant claims do not.
In response: In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the absence of oleic acid) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims 1-5 do not require the absence of oleic acid. While newly added claim 6 adds the limitation, it is addressed above in the U.S.C. 35 §103 rejection.
Applicant contends on pages 2-7 of the Remarks submitted on 27 April 2026 that alum and betulin are not interchangeable adjuvants.
In response: Applicant’s arguments with respect to claims 1-4 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The rejection above does not rely upon teachings of the use of alum in vaccines.
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
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