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 Status
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 26 January 2024, in which applicant; amended 3-8, 10-12, 14, 16-17. Therefore, claims 1-17 are pending in the application.
Election/Restrictions
Applicant’s election without traverse of Group I Claims 1-14 drawn to a method for producing a composition comprising parvoviral particles in the reply filed on 13 April 2026 is acknowledged.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-14 are under current examination.
Priority
This application was filed 12/20/2023 and is a 371 application of PCT/EP2022/066879 filed on 06/21/2022, which claims benefit to the foreign application EP21180623.7 filed on 06/21/2021.
Applicant files the certified English translation of the foreign application EP21180623.7 on 12/20/2023 is acknowledged. MPEP 2304.01(c). Thus, the earliest possible priority for the instant application is 06/21/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/26/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Title Objection
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. See MPEP 606.01
The following title is suggested:
“Method for producing parvoviral particles using a charge neutral surfactant.”
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.
Claim 1-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cardinal et al. (WO2020023612A1, cited in IDS filed 01/26/2024; hereinafter “Cardinal”) and evidentiary reference Wikipedia ("Lauryldimethylamine oxide" Wikipedia, 4 Dec. 2025. Web. 20 Jun. 2026; cited in PTO892).
Regarding claims 1, 4, and 8-10, Cardinal teaching is directed to the production of adeno-associated virus (AAV) particles for gene therapy and AAV formulations (abstract), wherein, the wild-type AAV viral genome can be modified to replace the rep/cap sequences with a nucleic acid sequence (i.e., a protein of interest [1064], (limitation of instant claim 9) including a payload region with at least one ITR region that generates AAV particles [0081] (limitation of instant claim 8). Cardinal further discloses the viral expression construct can contain parvoviral genes under control of one or more promoters include nucleotide sequences encoding non-structural AAV replication proteins, such as Rep genes which encode Rep52, Rep40, Rep68 or Rep78 proteins [0171]. Therefore, POSITA would anticipate that i) Cardinal teaching to culturing the cells are expressing a gene encoding parvoviral Cap protein [0364]; ii) lysing the cells using a charge neutral surfactant having a single linear alkyl chain (i.e., Lauryldimethylamine oxide (LDAO)) to obtain a lysate [0352]; iii) isolating the parvoviral particles from the lysate ([0362], [0364], Example 2, claims 1-3 and 7-10).
[AltContent: textbox ([img-media_image1.png]
Fig. from CAS (see the attached file))]Regarding claims 2-3, Cardinal teaches that the surfactant is a charge neutral with a single head group and a single tail ([0352], claim 8, see the CAS LDAO structure). Evidentiary reference Wikipedia (see the attached copy) discloses that LDAO is a zwitterionic surfactant. MPEP 2112.01 states that “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established,” In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). it is noted that the claimed wherein clauses do not recite any additional active method steps, but simply state a function, characterization or measurement of the results of product positively recited (e.g., zwitterionic,). In here, Cardinal et al., suggest producing the instant claim particle (i.e., parvoviral particles) specifically, using same cell culture method and product (i.e., LDAO). Accordingly, at the time of the invention POSITA would have anticipate that the charge neutral surfactant LDAO is a zwitterionic and has a single head group and a single tail, and this limitations are not unexpected.
Regarding claims 5-7, Cardinal teaches that the charge neutral surfactant is present during lysis at a concentration of at least 0.184% w/v, contains water, buffer and nuclease [0347], [0357].
Regarding claim 11, Cardinal teaches that the cells are insect cells, mammalian cells, or yeast cells [0280].
Regarding claims 12-13, Cardinal teaches that the genes encoding for the parvoviral proteins are expressed with a virus-based expression system using a helper virus [0285], wherein the helper virus is a baculovirus [0298].
Regarding claim 14, Cardinal teaches that the production method comprises:
i) clarification of the lysate, such as by centrifugation; ii) chromatography, such as affinity chromatography or ion exchange chromatography; and/or iii) filtration, such as nanofiltration, ultrafiltration, or diafiltration. [0365]-[0367]
Accordingly, Cardinal anticipates the instant claims 1-14.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Negrete et al., (Briefings in Functional Genomics and Proteomics, 7(4), pp.303-31, 2008, cited in IDS filed 01/26/2024; hereinafter “Negrete”), in view of Cardina et al., (WO2020023612A1, cited in IDS filed 01/26/2024; hereinafter “Cardinal”), and evidentiary reference Xu et al. (Appl Microbiol Biotechnol (2014) 98:3529–3538; cited in PTO892; hereinafter “Xu”).
Regarding claims 1, and 10-11, Negrete discloses a method of producing Adeno-associated virus (AVV) comprising i) culturing cell (i.e., Sf9 insect cells) that express Cap protein; ii) use of non-ionic detergents can be directly derived cell lysing and isolating virus-like particles (VLP) and iii) isolating VLP from lysate (Fig. 1, p. 307 left had col. 2nd ¶). Although produce cell is expressing Cap protein, and evidentiary reference Xu (see the attached copy) discloses that Yes, the Cap gene (short for capsid gene) is naturally a part of the viral genome that gets packaged inside the parvovirus particle (title, abstract and p. 3530 1st ¶ of Xu). MPEP 2112.01 states that “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established,” In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). it is noted that the claimed wherein clauses do not recite any additional active method steps, but simply state a function, characterization or measurement of the results of product positively recited (e.g., Cap protein). In here, Negrete et al., suggest producing the instant claim cell that express Cap protein specifically, using same cell culture method and product Cap protein Accordingly, at the time of the invention POSITA would have oblivious the Cap protein is a parvoviral particle and this limitations are not unexpected.
Although regarding claim 1, Negrete does not specifically teach non-ionic detergents having a single linear alkyl chain. However, such was known in the prior art.
Regarding claims 1-7, Cardinal teaching culturing the cells are expressing a gene encoding parvoviral Cap protein [0364]; ii) lysing the cells using a charge neutral surfactant having a single linear alkyl chain (i.e., Lauryldimethylamine oxide (LDAO)) to obtain a lysate [0352]; iii) isolating the parvoviral particles from the lysate ([0362], [0364], Example 2, claims 1-3 and 7-10). Cardinal teaches that the charge neutral surfactant is present during lysis at a concentration of at least 0.184% w/v, contains water, buffer and nuclease [0347], [0357].
Furthermore, as discussed above, Cardinal et al., suggest producing the instant claim particle (i.e., parvoviral particles) specifically, using same cell culture method and product (i.e., LDAO). Accordingly, at the time of the invention POSITA would have obvious to understand that the charge neutral surfactant LDAO is a zwitterionic and has a single head group and a single tail, and this limitations are not unexpected (MPEP 2112.01).
Accordingly, it would have been obvious to practice the culture method of Xu and include neutral surfactant LDAO in the medium as taught by Cardinal with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Cardinal because Lysis agents comprising detergents include non-ionic detergent helps to breaking cell membranes while preserving the native structure, stability, and functional activity of proteins ([0353] of Cardinal). The POSITA would have had a reasonable expectation of success in combining the teachings of Xu and Cardinal because each of these method teachings to generated parvoviral particles. Therefore, the products and method as taught by Xu et al. in view of Cardinal et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include LDAO of Cardinal had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate LDAO concentration and cell culture technology.
Regarding claims 8-9, Negrete discloses that the cells further express a gene encoding a parvoviral Rep protein and further comprise a nucleic acid construct comprising a gene of interest (e.g. green fluorescent protein, or coagulation factor IX) that is flanked by at least one parvoviral inverted terminal repeat (ITR) (p. 305 left-hand col. 1st ¶).
Regarding claims 12-13, Negrete discloses that the helper virus is a baculovirus (p. 305 left hand col.).
Regarding claim 14, Negrete discloses that the culture method comprises i) the supernatant containing the baculovirus is harvested by centrifugation to remove cells and cell debris (p. 305 right-hand col. 2nd ¶); ii) chromatography, such as affinity chromatography or ion exchange chromatography (p. 308 left-hand col. 4th ¶, Fig. 4); and/or iii) filtration, such as diafiltration (p. 308 left-hand col. 2nd ¶).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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