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 .
Claims 235-245 are pending.
Claim Objections
Claim 245 is objected to because of the following informalities:
The limitations of claim 245 are designated as (a), (b), and (b). The limitation should instead be designated as (a), (b), and (c). 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.
Claim 240 is 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 240 contains the trademark/trade name DoggyboneTM DNA. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a vector and, accordingly, the identification/description is indefinite.
Claims 239 and 242 recites the limitation “nucleic acid construct”. There is insufficient antecedent basis for this limitation in the claim.
Claims 239 and 242 recite the limitation “nucleic acid construct” without providing sufficient antecedent basic for the term. Claims 239 depends on claim 235. Similarly, claim 242 ultimately depends on claim 235. But the term “nucleic acid construct” is not defined in the claim 235. Accordingly, the claims are indefinite.
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)(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.
Claims 235-241, and 243-245 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Calos (US20060128020A1, published 15 June 2006).
Regarding claim 235, Calos teaches a vector comprising a sequence of interest flanked by first and second attachment sites recognized by a first site-specific recombinase and a third attachment site which is recognized by a second site-specific recombinase (paragraph 0196). The third attachment site will remain intact and associated with the expression cassette and will be available for use in site-specifically integrating the expression cassette into the target genome (see paragraph 0200).
Paragraph 0043 of Calos provides the definition of recombinase as family of enzymes that mediate site-specific recombination between specific DNA sequences recognized by the recombinase and further teaches that “integrase” is a subfamily within the recombinase family.
Figures 23A and 23B disclose an exemplary GFP-INTEC construct comprising a TP901-1 attB site, a GFP sequence, a ΦC31 attB site, and a TP901-1 attP site. In the presence of TP901-1 integrase, a circular GFP-INTEC comprising the GFP sequence, a hybrid TP901-1 attachment site, and the ΦC31 attB site is generated. Thus, the TP901-1 attB and TP901-1 attP sites correspond to the claimed first and second cognate integrase recognition sites, the GFP sequence corresponds to the claimed cargo polynucleotide construct, and the ΦC31 attB site corresponds to the claimed third integrase recognition site.
Calos teaches that, when the first, second and third attachment sites flank the sequence of interest, exposure to the unidirectional site-specific recombinase that recognizes the first and second attachment sites creates a circular vector including the sequence of interest, a hybrid attachment site (hybrid of the first and second sites) and the third attachment site (paragraph 0193). Figure 22A of Calos particularly teaches upon exposure of the vector to the first recombinase, which recognizes the first and second attachment sites, recombination of the first and second attachment sites generates a circular integrating expression cassette vector (INTEC).
Paragraph 0199 of Calos further teaches that the attachment sites recognized by different unidirectional site-specific recombinases are distinct and do not cross-react. Thus, the ΦC31 attB site is orthogonal to the TP901-1 attachment sites used for formation of the circular donor.
Calos further teaches that the third attachment site remains intact following the first recombination and is available for site-specific integration of the expression cassette into the target genome (see 0200). Figure 23B expressly illustrates that, in the presence of ΦC31 integrase, the circular GFP-INTEC is integrated into the genome of K562 cells, with the circular donor’s ΦC31 attB attachment site participating in formation of hybrid ΦC31 attachment sites at the genomic integration site.
See below figures 22A, 23A, and 23B from Calos.
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Regarding claim 236, Calos teaches that the third attachment site remains intact following the first recombination and is available for site-specific integration of the expression cassette into the target genome (see 0200). Figure 23B expressly illustrates that, in the presence of ΦC31 integrase, the circular GFP-INTEC is integrated into the genome of K562 cells, with the donor’s ΦC31 attB site participating in formation of hybrid ΦC31 attachment sites at the genomic integration site.
Regarding claim 237, Calos teaches that the sequence of interest is flanked by a first recombination site (e.g., attB site for a first recombinase “attB 1”) and a second recombination sites (e.g., a second recombination site comprising an attP site for the first recombinase, “attP1,” (see paragraph 0212 and figure 22A).
Regarding claim 238, Calos teaches that the gene of interest is GFP expression cassette (see figures 22A, 23A, and 23B).
Regarding claim 239, Calos teaches that the nucleic acid construct is a DNA construct (see paragraph 0079). In particular, Calos describes a plasmid comprising a GFP expression cassette and the attachment sites and describes generation of circular GFP-INTEC DNA donor from the plasmid (see figure 23A).
Regarding claim 240 and 241, Calos teaches that viral vector delivery vehicles include, but are not limited to: adenovirus, herpesvirus, lentivirus, vaccinia virus and adeno-associated virus (AAV) (see paragraph 0173).
Regarding claim 243, Calos teaches that expression cassettes, targeting constructs, vectors, recombinases and recombinase-coding sequences of the present invention can be formulated into kits with the kits including containers, instructions, solutions, buffers, etc. (see paragraph 0217). When the nucleic acid construct is mixed with solutions or buffer, that meets the requirement of pharmaceutical composition as recited in claim 243.
Regarding claim 244, Calos teaches that the invention comprise a method of treating disorders in a subject in need of such treatment (see paragraph 0254) and disorders includes monogenic disorders, infectious diseases, acquired disorders, cancer, and the like (see paragraph 0255). Furthermore, examples 9 of Calos teaches about treating sickle cell anemia by using φC31 integrase to place a plasmid carrying attB and an expressed γ-globin or a mutant anti-sickling β-globin into the genomes of hematopoietic stem cells of the patient (see paragraph 0737).
Regarding claim 245, Calos teaches an in vitro method for generating a pure expression cassette vector where in the expression cassette is flanked by attachment sites with a unidirectional site-specific recombinase (See paragraph 0195 and figure 22A). Calos further teaches use of a second site-specific recombinase to integrate the resulting circular vector into a genomic target site (see paragraph 0193, 0196, and Figures. 22A AND 23B). The remaining limitations of claim 45 are taught by Calos as discussed above with respect to claim 235.
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.
Claim 242 is rejected under 35 U.S.C. 103 as being unpatentable over Calos (US20060128020A1, published 15 June 2006) as applied to claims 235-241, and 243-245 above, and further in view of Feala (WO2021016075A1, published 28 January 2021).
Regarding claim 242, Calos does not explicitly teach 5’ inverted terminal repeat and 3’ inverted terminal repeat wherein 5’-and-3’ terminal repeat flanks the first and second integration recognition site. However, presence of 5’ and 3’ ITRs is required for any AAV vector to function.
For example, Feala teaches an AAV viral vector comprising 5’-and-3’ITR regions flanking the recombinase recognition site. Specifically, example 18 of Feale teaches that AAV6 template DNA comprise, in order, 5’ ITR, a recombinase recognition site, a pol II promoter, a human fetal g-globin coding sequence, a poly A tail and 3’ITR (see page 294, line 4-17).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have included 5’ and 3’ ITRs in the AAV vectors taught by Calos since such is a requirement for the construction of an AAV vector. An ordinary skill in the art would have been included ITRs in AAV vector because ITRs are cis-acting element of AAV vector and are required for viral packaging, protection, and delivery of the nucleic acid construct.
In view of the foregoing, claim 242 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SURAJ SAPKOTA whose telephone number is (571)270-0842. The examiner can normally be reached Monday-Thursday 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram R Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Suraj Sapkota
Patent Examiner
AU 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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