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 .
Response to Amendment/Disposition of Claims
Applicant’s Amendment filed on 12 December 2025 has been received and entered. Claims 72-94 were pending. Claims 72, 81, 88-89, and 91-92 have been amended. Claims 1-71, 77-78, and 90 have been cancelled. No new claims have been added.
Accordingly, Claims 72-76, 79-89, and 91-94 are currently pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0220356 A1, Published 13 July 2023. Applicant’s amended Specifications as presented on 12 December 2025, 01 November 2022, 15 September 2022, and 25 April 2022 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Of note, there is still not an attorney of record on file due to a lack of an official power of attorney of record. While a customer number has been provided on the ADS submitted 25 April 2022, this is not the equivalent of a power of attorney or an authorization to act in a representative capacity. In order to expedite prosecution in the instant application, it is suggested that a power of attorney be filed as per MPEP §402 or MPEP §1807, or an Authorization to Act in a Representative Capacity be filed as per MPEP §403 in order for the Office to freely and openly discuss the merits of the case with the applicant's representative(s). Please refer to the MPEP or http://www.uspto.gov/patents/law/poafaqs.jsp#a if you have questions regarding the proper filing of a power of attorney.
Response to Arguments
Applicant's arguments filed 12 December 2025 regarding the previous Office action dated 17 September 2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Specification
(Objections withdrawn) – The objections to the Abstract of the disclosure for containing implied language and minor informalities are withdrawn in light of the amendments to the Abstract.
(Objection withdrawn) – The objection to the disclosure for containing possible minor errors is withdrawn in light of the amendments to the Specification.
Claim Objections
(Objection maintained) – The objection to Claims 72 and 91-92 for containing more than one period is maintained.
(Objection withdrawn) – The objection to Claim 72 for containing minor informalities is withdrawn in light of the amendments to the claim.
(Objection maintained) – The objection to Claim 73 for containing minor informalities is maintained.
(Objection withdrawn) – The objection to Claims 90-92 for containing an undefined abbreviation is withdrawn in light of the cancellation of one of the claims and the amendments to the remainder of the claims.
Response to Arguments
Applicant's arguments filed 12 December 2025 with respect to the objection to Claims 72 and 89-92 for containing multiple periods have been fully considered but they are not persuasive.
In their Response, Applicant argues that “Applicant has amended claims 72, 73, and 89-92 to address the informalities and, accordingly, requests withdrawal of the objections” (see Page 1 of Remarks, Last Paragraph). This is not entirely accurate. Applicant failed to address the objections to Claims 72, 91, and 92 with regard to the claims containing multiple periods. As such, this objection is withdrawn with respect to Claim 89, which was amended appropriately, and Claim 90, which was cancelled, but is maintained with respect to Claims 72, 91, and 92.
Applicant's arguments filed 12 December 2025 with respect to the objection to Claims 72-73 and 89-93 for containing minor informalities have been fully considered but they are not persuasive.
In their Response, Applicant argues that “Applicant has amended claims 72, 73, and 89-92 to address the informalities and, accordingly, requests withdrawal of the objections” (see Page 1 of Remarks, Last Paragraph). This is not entirely accurate. Applicant failed to address the objection to Claim 73. As such, this objection is withdrawn with respect to Claims 72 and 89-92, but is maintained with respect to Claim 73. Claims 72, 91, and 92 are also objected to for still containing multiple periods, as noted above.
(New Objection) – Claim 81 is objected to because of the following informalities: it is suggested that it say “sodium chloride (NaCl)”. There should be parentheses around “NaCl”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
(Rejection withdrawn) – The rejection of Claim 81 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn) – The rejection of Claim 88 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Note: for the purposes of examining these claims on their merits, the term “hydrodynamic radius” will be interpreted as referring to its plain meaning since no special definition was provided in the instant Specification, i.e., the radius of a hypothetical sphere that diffuses at the same rate as the particle or molecule in question, under the same conditions. Additionally, the term “alkylating agent” in Claim 92 will be interpreted to encompass formalin, as disclosed in the instant Specification (see Paragraph 0127). No special definition is provided in the instant Specification for “formalin”, so Examiner is using what is understood to be the standard definition of formalin (i.e., formalin is the name for saturated [37%]formaldehyde solution) as starting point. Since Applicant did not specify a certain percentage of formalin in the claims, however, Examiner is interpreting “formalin” as reading upon any formaldehyde treatment (e.g., 10% formalin is roughly equivalent to 4% formaldehyde), which is encompassed by the term “alkylating agent”. Regarding Claim 80, the presence of NaCl will be treated as optional since the claim recites a concentration as low as 0 mM (i.e., not present).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(Rejection withdrawn) - The rejection of Claims 72-73, 75, 77, 80, 84, and 93 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost (US 2009/0304729 A1) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn) – The rejection of Claim 89 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost (US 2009/0304729 A1) is withdrawn in light of the amendments to the claim.
(Rejection withdrawn) – The rejection of Claim 90 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost (US 2009/0304729 A1) is withdrawn in light of the cancellation of the claim.
(Rejection withdrawn) – The rejection of Claim 91 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost (US 2009/0304729 A1) is withdrawn in light of the amendments to the claim.
(Rejection maintained) – The rejection of Claim 92 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost (US 2009/0304729 A1, Published 10 December 2009) is maintained.
Response to Arguments
Applicant's arguments filed 12 December 2025 with regard to the rejection of Claim 92 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost have been fully considered but they are not persuasive.
In their Response, Applicant argues that independent claim 72 has been amended “to recite ‘a reagent comprising at least one non-ionic surfactant and cetrimonium bromide (CTAB), wherein the concentration of the CTAB ranges from about 1.25 g/L to 3.0 g/L” (see Page 2 of Remarks, Paragraph 5) and that though “different in scope, amended independent claims 89, 91, and 92 recite similar features as allowable claim 72” (see Page 3, Paragraph 2). This is not entirely accurate. While independent Claims 72, 89, and 91 have been amended to recite the claimed concentration range of CTAB, amended independent Claim 92 does not recite this concentration range, or any for that matter. Claim 92 now simply recites CTAB as the ionic surfactant, a limitation which Gregersen and Kost already meets (see Paragraphs 0085-0086, 0129). Gregersen and Kost already met the rest of the claim limitations, as noted in the previous Office Action. As such, Gregersen and Kost still meet all of the claim limitations of amended independent Claim 92. Therefore, the rejection of Claim 92 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gregersen and Kost is maintained.
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.
(Rejection maintained) – The rejection of Claims 74, 76, 79, 81-83, 85-88, and 94 under 35 U.S.C. 103 as being unpatentable over Gregersen and Kost (US 2009/0304729 A1, Published 10 December 2009) as applied to claims 72-73, 75, 80, 84, and 93 previously, and further in view of Haussmann (WO 2009/115917 A2, 24 September 2009) (cited by Applicant on IDS filed on 25 April 2022), Garcon et al. (WO 02/067983 A1, Published 06 September 2002), and Felgenhauer et al. (US 2017/0327559 A1, Published 16 November 2017) is maintained.
Response to Arguments
Applicant's arguments filed on 12 December 2025 with regard to rejection of Claims 74, 76, 78-79, 81-83, 85-88, and 94 under 35 U.S.C. 103 as being unpatentable over Gregersen and Kost as applied to claims 72-73, 75, 77, 80, 84, and 93 previously, and further in view of Haussmann, Garcon et al., and Felgenhauer et al. have been fully considered but they are not persuasive.
In their response, Applicant argues that a “concentration reciting (v/v) units is not equivalent to Applicant’s concentration reciting g/L units. Moreover, the ordinary artisan would recognize that (v/v) units cannot simply be converted to arrive at g/L units, as the Office has alleged. And, even if convertible, there is no guidance in Felgenhauer for arrive at Applicant’s narrow claimed range of “about 1.25 g/L to 3.0 g/L” of CTAB from Felgenhauer’s broad teaching of about 0.01% to about 1.0% (v/v). Furthermore, Felgenhauer’s disclosure of surfactant concentrations relates to sufficiency to promote aggregation between surfactants and lipo-protein membranes. Applicant’s CTAB concentration, on the other hand, serves an entirely different purpose, as recited in the claims: inactivating and splitting viral particles. Thus, the Office’s reliance on Felgenhauer is improper at least in view of the above.”
Applicant’s argument regarding Felgenhauer’s disclosure of surfactant concentrations relates to sufficiency to promote aggregation between surfactants and lipo-protein membranes appears to be referring to Paragraph 0024 of Felgenhauer, which has to do with the organic solvent, not the surfactant. Paragraph 0030 of Felgenhauer refers to the surfactant and specifically states that its purpose is for inactivating virus. As such, this aspect of Applicant’s argument is not found persuasive. Furthermore, even if the purposes of the reagents of the instant claims are different for the prior art and Applicant, this does not obviate the rejection. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
The office agrees that the value amplitudes of v/v units may not match value amplitudes of equivalent concentration in g/L units. However, the office does not agree that one cannot convert between the units as this requires only known relationships between concentration, molecular weight, etc.
Regarding Applicant’s argument regarding the instant concentration range and the prior art concentration range of CTAB, this is also not found persuasive, as the claims recite a concentration of CTAB ranging “from about 1.25 g/L to 3.0 g/L” (emphasis added). Applicant’s use of the word “about” undermines their argument as they do not provide a clear definition for this word in the instant Specification. Applicant attempts to define this term (see Paragraphs 0066-0067), but fails, mainly because it uses “about” in the definition of “about”. The prior art reference recites about the same concentration recited in the instant claims due to the use of the word “about” in the claim language because of the definition, or lack thereof, of the term in the instant Specification. Therefore, the rejection of Claims 74, 76, 79, 81-83, 85-88, and 94 under 35 U.S.C. 103 as being unpatentable over Gregersen and Kost as applied to claims 72-73, 75, 80, 84, and 93 previously, and further in view of Haussmann, Garcon et al., and Felgenhauer et al. is maintained but is withdrawn as it relates to Claims 77-78 in light of the cancellation of these claims.
(New Rejection – necessitated by amendment) – Claims 89 and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Gregersen and Kost (US 2009/0304729 A1, US 2009/0304729 A1, Published 10 December 2009) (cited in a previous Office Action) and Felgenhauer et al. (US 2017/0327559 A1, Published 16 November 2017) (cited in a previous Office Action).
Gregersen and Kost teach a method for producing a viral vaccine comprising immunogenic proteins derived from a virus, such as Influenza virus, propagated on cell culture (see Abstract; Paragraphs 0028-0030, 0055). Specifically, they teach a method wherein the vaccine is prepared from viruses which are propagated on cell culture (see Paragraphs 0065-0066), and wherein the viral particles are purified from the cell culture (see Paragraph 0058). They also teach inactivating and splitting the purified viral particles to generate a sub-virion form of the virus, such as a split virus, using a non-ionic surfactant such as polysorbate 80, an ionic surfactant such as myristyltrimethylammonium salt (see Paragraphs 0084-0086, 0129). Additionally, Gregersen and Kost teach a method of purifying sub-virions after splitting (see Paragraphs 0026, 0084, 0087, 0129).
Gregersen and Kost also teach a method for producing a viral vaccine comprising immunogenic proteins derived from a virus, such as Influenza virus, propagated on cell culture (see Abstract; Paragraphs 0028-0030, 0055). Specifically, they teach a method wherein the vaccine is prepared from viruses which are propagated on cell culture, such as Madin-Darby Canine Kidney (MDCK) cells (see Paragraphs 0065-0066), and wherein the viral particles are purified from the cell culture (see Paragraph 0058). They also teach inactivating and splitting the purified viral particles to generate a sub-virion form of the virus, such as a split virus, using a salt such as myristyltrimethylammonium salt, which also happens to be an ionic surfactant, specifically a cationic surfactant (see Paragraphs 0084-0086, 0129). Additionally, Gregersen and Kost teach a method of purifying viral proteins from purified viral particles and/or sub-virions (see Paragraphs 0026, 0084, 0087).
While the instance claim recites a salt, no further definition is provided for is encompassed by this term. As such, it reads on any and all salts, such as myristyltrimethylammonium salt, as recited in the prior art reference. Furthermore, the prior art method also calls for the use of BPL as an alkylating agent, which has the additional benefit of reducing aggregation (i.e., particle size).
Gregersen and Kost do not teach a specific concentration range of CTAB.
Felgenhauer et al. teach a method for inactivating lipid-coat containing viruses, such as Orthomyxoviruses like Influenza virus, using surfactants, such as CTAB. Felgenhauer et al. also teach that said surfactants can be used at final concentration ranging from about 0.01% to about 1.0% (v/v) (see Abstract; Paragraphs 0011, 0027). The instant claims recite a range of about 1.25 g/L to 3.0 g/L, which is equivalent to the prior art range due to Applicant’s use of the term “about” in the claim set and the lack of a clear definition. As such, Felgenhauer et al. meet this claim limitation.
It would have been obvious to a skilled artisan to modify the teachings of Gregersen and Kost with those of Felgenhauer et al. in order to develop methods for producing an Influenza virus vaccine. The inactivation method of Felgenhauer et al., while not directed toward viral vaccine, is applicable because it would render the viral vaccine safe for administration and would provide an efficient means for inactivating and splitting the viral particles to generate sub-virions, as disclosed by Gregersen and Kost. The method of Gregersen and Kost also involved the use of an alkylating agent, BPL, which provides the additional benefit of reducing aggregation. Gregersen and Kost teach that vaccine formulations with reduced aggregates may also have improved immunogenicity and that the immunogenicity of a vaccine relies upon the specificity of antibodies for particular viral epitopes. They also teach that if the surface of a protein is hidden through aggregation in large macromolecules, then the epitopes may become less recognizable and therefore less effective in the vaccine. Additionally, they teach that if the protein is structurally modified by the presence of aggregates, it may not be recognized and subsequently removed during purification instead of being retained. As such, it would have been obvious to a skill artisan to combine the disclosed methods in order to maximize the amount of viral vaccine obtained and the maximize the immunogenicity of said vaccine, which would make it and the process to produce it more effective. Additionally, optimization is not patentable. “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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 (CCPA 1955).
Such modifications, combining prior art elements according to known methods in order to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 89 and 91 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Cui et al. (WO 2013/010797 A1, Published 24 January 2013)
Cui et al. teach a method for the production of viral antigen derived from an enveloped virus as well as using said method for the production of a vaccine. This reference has not been utilized, as rejection would have been redundant to those set forth above.
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 CAREY A STUART whose telephone number is (703)756-4668. The examiner can normally be reached Monday - Friday, 7:30 AM - 4:30 PM EST.
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, Michael Allen can be reached at 571-270-3497. 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.
/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671