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 Interpretation
Claims 25 and 30 depends from claim 8, and recites a final concentration of MgSO4. Claim 8 recites MgSO4 as a member of a Markush grouping of salts. Accordingly, claims 25 and 30 are interpreted as specifying the final concentration of MgSO4 when MgSO4 is selected from the Markush grouping, and as not requiring the salt used to be MgSO4.
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 14, 18, 21, 22, 25, 30 and 37 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.
Claims 14, 18, 21, 22, 25, 30 and 37 use the term “about”. A review of the Specification has not revealed a definition or discussion for what is meant by the term “about”. Therefore, the scope of these claims is unclear and indefinite.
Claims 18 and 22 recite a limitation with the terminology “and optionally about 0.05% (w/v)” (claim 18) and “optionally about 50mM” (claim 22). The claims fail to particularly point out and distinctly claim the subject matter as it is unclear whether the phrase “ optionally about” is intended to further limit the concentration(s) or provide an alternative concentration or merely limit the range.
Claims 25 and 30 recite MgSO4 and are dependent on claim 8, which provides a Markush listing of modifiers that are salts. Thus, the claims is indefinite since it is unclear if MgSO4 is required as a limitation in the dependent claims
Claim 45 recites the use of the language in parenthesis: "(including AAV3A or AAV3B)" which is indefinite since it is unclear if the claim requires AAV3, or a more narrow scope of AAV3A or AAV3B.
Claim Rejections - 35 USC § 102
(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.
Claims 1, 4-8,12, 14,16,18,21,22,25,29,30,37, 40, and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murphy et al., (Purification Process for Plasmid DNA; US 7767399 B2; published 03-08-2010).
Regarding claims 1, 4 and 5, Murphy et al., discloses a purification step that is a two-part lysis/lysate clarification procedure involving, as a detergent, a long chain quaternary ammonium salt that is cyltrimethylammonium bromide (CTAB) (column 55 and 56, claims 16 and 21(g)). A cell lysate is first generated, from host cells in a buffered solution that is physiologically compatible (column 53, ‘Example 9, paragraph 3’), containing host DNA, and said cell lysate is then clarified by flocculation to remove host cell debris and combined with DNA purification methods known in the art (column 9, lines 39-46).
Regarding claims 6-8 and 12, Murphy et al., discloses the use of sodium chloride (NaCl) as a modifier, cells suspended in STET buffer are further incubated as a 50% slurry w/v with a PEG6000 solution suspended in a 150mM NaCl solution for 1 hour (column 51, Example 8, lines 31-33), prior to CTAB treatment (column 51, Example 8, lines 43-55) .
Regarding claims 14, 16, 18, 21, 22, 25, 29, 30 Murphy et al., discloses cells were suspended to a concentration according to an O.D.6oo of 45, approximately 3.6 x1010 cells/ml (column 7, lines 1-3) . Additionally, Murphy et al., discloses the isolation of DNA from mammalian cells (column 18, lines 36-54) (claim 16). Murphy et. al., also discloses “a CTAB low-cut precipitation step can be performed to about 0.15% (w/v)… a CTAB precipitation [in which] DNA is precipitated from the clarified host cell lysate with a single 0.50% w/v CTAB-induced precipitation step...” (column 51, Example 8, lines 43-52) (claim 18). Further, a 2% (w/v) CTAB in 40mM NaCl (claim 22) can be added to a cell lysate, bringing the final concentration to 0.15% (column 22, lines 58-61)—steps are performed in buffered solutions(s) that are physiologically compatible. Within CTAB precipitation steps, a clarified lysate is filtered (claim 29) and the filter cake further washed (column 51, Example 8, lines 51-57).
Regarding claim 37, Since Murphy et al., performs the claimed method, and does not require preparing lysates using octoxynol-9 and/or domiphen bromide, the resulting amount of vector genomes is 1.5 to 10-fold or more, as required by the claim.
Further, with regards to claim 25 and 30, MgSO4 is recited in the Markush grouping in the alternative. Since the prior art teaches sodium chloride, which is also from the Markush grouping, it anticipates the claim limitation.
Regarding claims 40 and 52, Murphy et al., discloses the lysis and flocculation procedure may be combined with a novel downstream polishing step, encompassing precipitation of clinical-grade plasmid DNA and purification steps which provides DNA that can be used in other procedures; use in therapeutics, including gene therapy (column 6, lines 15-21).
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.
Claims 41 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al., (Purification Process for Plasmid DNA; US 7767399 B2; published 03-08-2010) as applied to claims 1, 4-8,12, 14,16,18,21,22,25,29,30,37, 40, and 52 above, and further in view of Large, E.E. et al. Adeno-associated virus receptor complexes and implications for adeno-associated virus immune neutralization. Frontiers in Microbiology.09, February 2023; (14): pp.1-10.
The teaching of Murphy et al., are previously discussed.
Murphy et al. further teaches downstream DNA purification that are pharmaceutical and/or clinical grade for gene therapy.
Murphy et al., does not teach recombinant virus serotypes of AAV (claim 41) and binding capacities to heparan sulfate proteoglycan (HSPG) compared to binding to sialic acid or galactose (claim 45).
However, regarding claims 41 and 45, Large, et al teaches a summation of studies which illustrates the following affinity patterns for binding by AVV serotypes (page 2, “AAV glycan attachment factors”):
heparan sulfate (HSPG) and sialic acid (SIA) are negatively charged whereas the third, galactose, is uncharged
HSPG is known to be important for the cellular attachment of serotypes AAV2, 3B, 6 and 13
AAV1, 5, and 6 use SIA and
AAV9 uses galactose to attach to cells
Glycans with a terminal SIA were found to be important for AAV1, 4, 5, and 6
Glycans with a terminal galactose were implicated in AAV9 cellular entry
Structures for AAV1 and AAV5 complexed with SIA and, more recently of galactose bound to AAV9 have revealed that HSPG, SIA, and galactose glycan attachment sites are mostly distinct.
One of ordinary skill in the art at the effective date of filing would have recognized that the methods described by Murphy et al., combined with Large et al., would provide for “pharmaceutical and/or clinical grade” DNA useful in downstream procedures to produced recombinant AAV particles for the purposes of gene therapy and/or other procedures in which AAV serotypes are able to bind to specific cell receptors with HSPG, and introduce genetic/genomic materials to tissues.
The motivation to combine said methods are to produce therapeutic viral particles that are able to bind to mammalian tissue receptors and introduce genetic material that can modify a disease-specific genetic sequence in cells and/or translate them into proteins to circumvent a disease-specific variant, to then ameliorate and/or reduce phenotypic traits associated with disease. One would expect success with the combination of said methods: as (1) Murphy et al., teaches the use of purified DNA using methods that require CTAB, a modifier salt, and buffered solutions with cell concentrations, resulting in the same outcome as the instant application; (2) Large et al., teaches the differing binding traits of the specified AAV serotypes (used as recombinant vectors) to HSPG and/or sialic acid and galactose. Therefore, the combined art is able to perform the same methods and produce the same outcome as the instant application.
Conclusion
No claims are deemed patentable.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ENUSHA KARUNASENA whose telephone number is (571)272-3972. The examiner can normally be reached Monday-Friday 7:30am-5pm.
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, Sharmila Landau can be reached at 571-272-0614. 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.
/ENUSHA KARUNASENA/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
Prosecution Insights