DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The instant application is a Continuation (CON) of prior-filed U.S. Application No. 16/749,461 (filed 11/09/2015, now abandoned), which is a CON of prior-filed U.S. Application No. 14/935,866 (filed 11/09/2015, now U.S. Patent No. 10,577,589), which is a CON of prior-filed U.S. Application No. 13/769,025 (filed 02/15/2013, now U.S. Patent No. 9,217,160), which is a CON of prior-filed Application No. PCT/US2011/048006 (filed 08/16/2011), which claims benefit of U.S. Provisional Application No. 61/374,198 (filed 08/16/2010).
Response to Amendments
The amendment filed on 02/19/2026 has been received and entered into the application file.
Claims 1, 3-4, 6-8, 10, and 12-16 are pending and examined on the merits herein.
Status of Prior Rejections/Response to Arguments
RE: Rejection of:
claims 1-2 and 5-18 under pre-AIA 35 U.S.C. 103(a) over Bennett in view of Elledge and Gibson;
claim 3 under pre-AIA 35 U.S.C. 103(a) over Bennett in view of Elledge and Gibson, further in view of McVey; and
claim 4 under pre-AIA 35 U.S.C. 103(a) over Bennett in view of Elledge and Gibson, further in view of Gao:
The cancellation of claims 2, 5, 9, 11, and 17-18 renders the rejections thereof moot.
The amendment to claim 1 incorporates limitations of original claims 2, 5, 9, and 11. Additionally, the limitations of original claim 11 (now present in claim 1) and claim 12 have been amended to change the previous product-by-process limitations of the linearized adenoviral gene modules and destination vector backbone to active steps; i.e., the gene modules and backbone are now required to be linearized from circular molecules or plasmids according to their respective claims in the method of the instant invention.
The amendments changing the previous product-by-process limitations to active steps is sufficient to change the scope of the claimed method, and therefore is sufficient to obviate the remaining rejections of record. Accordingly, the rejections are withdrawn. However, in the interest of compact prosecution, the arguments set forth by Applicants will now be addressed in the context of the currently amended claims.
Applicants’ arguments hinge on the assertion Bennett, et al. does not teach a hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module; i.e., disclosure the “segments” may comprise recited features is not disclosure of the presently claimed hybridization competent adenoviral destination vector backbone. Applicants further assert the Office has not articulated why a person having ordinary skill in the art would modify the cited disclosure of “segments” to arrive at the claimed limitations.
Respectfully, these arguments are not found persuasive.
Regarding the hybridization competent limitation: As set forth in the Claim Interpretation section of the non-final Office action dated 08/21/2025, and absent of a clear definition in the specification of the instant application, the term hybridization competent is interpreted as an adjective to describe the relevant adenoviral components as capable of hybridizing; i.e., the capability of the nucleic acid(s) comprising the vector and one or more gene module(s) to form a double-stranded molecule from two complementary single-stranded molecules. Bennett, et al. teaches the segments which comprise the modular system for adenovirus construction are combined to produce a nucleic acid molecule; thus, Bennett, et al. implicitly teaches hybridization competent segments. This is evidenced throughout the disclosure; see e.g., pars. 0079, 0080, and Figs. 5D-F.
Regarding the adenoviral destination vector backbone: The amendment to claim 1 recites the hybridization competent adenoviral destination vector backbone comprises a core module comprising an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module. As a first matter, there is no clear definition of the term core module in the instant disclosure, nor is it a term widely used in the art. In the context of the instant claims, it appears the “core module” of the vector backbone refers to a “module” comprising specific regions of the adenoviral genome, wherein said “core module” is a required component of the recombinant adenovirus vector. As a second matter, the word backbone as it pertains to an adenoviral vector is interpreted as its plain meaning. As evidenced by Garren, et al. (US 2010/0048679), "vector backbone" refers to the portions of a plasmid vector other than the sequence encoding a self-antigen, -protein, -polypeptide, or -peptide (par. 0060); a backbone is an inherent component of all plasmids and vectors.
Bennett, et al. teaches a segment of the adenoviral genome which may comprise one or more regions of the genome, e.g., left ITR, right ITR, packaging signal, E1, E2, E3, E4, and/or one or more late regions (par. 0305); as evidenced by Danthinne and Imperiale, the adenovirus genome comprises five late regions: L1, L2, L3, L4, and L5 (Fig. 1). As Bennett, et al. teaches an embodiment wherein a segment comprises an E2 region and multiple late regions, the disclosure implicitly and necessarily teaches an embodiment wherein a segment comprises an E2 region, an L1 region, an L2 region, an L3 region, and an L4 region (i.e., an E2-L4 “core module”). Bennett, et al. does not explicitly designate this embodiment as a backbone, but nevertheless teaches an embodiment wherein a recombinant adenoviral vector comprises a segment which satisfies the limitations in the claim (see e.g., pars. 0172, 0196-0198, 0204, 0305, 0321).
Further, the instant claim recites a hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module; the transitional term “comprising” is inclusive or open-ended, and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03(I). In regards to “core module”, there is no need to establish a prima facie case of obviousness for a disclosed embodiment. In regards to the vector backbone comprising said “core module”, a vector comprising a segment which satisfies the core module limitations necessarily reads on a vector backbone comprising said core module.
For at least the reasons set forth above, Applicants’ arguments are found unpersuasive; therefore, in view of amendments, modified rejections are set forth below.
RE: Rejection of:
claims 1-16 and 18 on the ground of nonstatutory double patenting over claims 1-20 of U.S. Patent No. 9,217,160;
claims 1-16 and 18 on the ground of nonstatutory double patenting over claims 1-15 of U.S. Patent No. 10,577,589; and
claim 17 on the ground of nonstatutory double patenting over claims 1-20 of U.S. Patent No. 9,217,160 and claims 1-15 of U.S. Patent No. 10,577,589, each in view of Bennett:
The cancellation of claims 2, 5, 9, 11, and 17-18 renders the rejections thereof moot.
Applicants have requested the nonstatutory double patenting rejections be reconsidered in view of the amendments, or held in abeyance until allowable claims have been identified.
Respectfully, Applicants are reminded 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Nonstatutory double patenting rejections may not be held in abeyance. See MPEP 714.02.
Accordingly, the remaining rejections are maintained, with modifications as necessitated by amendment set forth below.
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claims 1, 3-4, 10, 12, 16: These claims recite the term hybridization competent in the context of adenoviral destination vectors and adenoviral gene modules; e.g., as claim 1 recites, “…by combining a hybridization competent adenoviral destination vector…with one or more hybridization competent adenoviral gene modules…”. In the absence of a clear definition in the specification of the instant application, the term hybridization competent is interpreted as an adjective to describe the relevant adenoviral components as capable of hybridizing; i.e., the capability of the nucleic acid(s) comprising the destination vector and one or more gene module(s) to form a double-stranded molecule from two complementary single-stranded molecules.
Regarding claims 1, 6-8: These claims recite the term core module in the context of an adenoviral destination vector; e.g., as claim 1 recites, “…a hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module…”. It is noted the specification of the instant application appears to describe a core module as comprising the entirety of gene modules E2, L1, L2, L3 and L4 (par. 0014; Fig. 5). It is also noted that, while no clear definition of core module is set forth in the specification of the instant application, a core macromodule is described in par. 0085 as comprising an E2-L4 macromodule, i.e., a nucleic acid including an E2-L2 module and an L3-L4 module. In par. 0092, the specification further recites, “[a] ‘core macromodule’ (also referred to herein as an “E2-L4 macromodule”), as used herein, refers to a nucleic acid containing at least one of a viral DNA polymerase coding region and a hexon coding region.” Thus, it appears the terms core module and core macromodule are synonymous.
However, in the absence of a clear definition, in order to give the scope of the instant claims their due breadth under broadest reasonable interpretation, the word core in the term core module is not given any patentable weight. For example, claim 1 recites, “…a hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module …”; under broadest reasonable interpretation, an adenovirus vector comprising an E2-L2 module reads on the wherein the hybridization competent adenoviral destination vector is an adenovirus core module destination vector limitation.
Regarding claims 1, 3-4, 10, 12: These claims recite the term hybridization competent adenoviral destination vector backbone. The word backbone as it pertains to an adenoviral vector is understood as meaning the DNA sequence comprising the vector. As evidenced by Garren, et al. (US 2010/0048679), "vector backbone" refers to the portions of a plasmid vector other than the sequence encoding a self-antigen, -protein, -polypeptide, or -peptide (par. 0060); a backbone is an inherent component of all plasmids and vectors. Inherent components of elements recited have antecedent basis in the recitation of the elements themselves. See MPEP 2173.05(e); see Bose Corp. v. JBL, Inc., 274 F.3d 1354, 1359, 61 USPQ2d 1216, 1218-19 (Fed. Cir 2001).
Maintained/Modified Prior Art Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 6-8, 10, and 12-16 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bennett, et al. (US 2004/0219516), in view of Elledge (US 2007/0292954) and Gibson, et al. (Nat Methods. 2009); as evidenced by Danthinne and Imperiale (Gene Ther. 2000).
Bennett, et al. teaches compositions and methods for the construction of nucleic acids comprising all or a portion of a viral genome (Abstract).
Elledge teaches methods for cloning DNA by homologous recombination (Abstract).
Gibson, et al. teaches an assembly method for the construct of synthetic and natural genes, genetic pathways, and entire genomes (Abstract).
Regarding claims 1, 6-8, 10, 12: Bennet, et al. teaches a method of constructing a nucleic acid molecule comprising all or a portion of an adenoviral genome (par. 0033), wherein the nucleic acid molecules are packaged into a viral particle in trans; e.g., on separate nucleic acid molecules (par. 0039). In an embodiment, the adenoviral genome is constructed by combining two or more nucleic acid segments by a recombination reaction (par. 0037). This reads on the method of making a recombinant adenovirus, comprising assembling an adenovirus genome limitation recited in claim 1. Bennett, et al. implicitly teaches the nucleic acid molecules as single-stranded and capable of forming a double-stranded molecule by bonding to its complement (see e.g., pars. 0079-0080, 0202, 0210, 0315, Fig. 1, Fig. 27A-B); this reads on the hybridization competent limitations recited in the instant claims.
Bennett, et al. teaches a circular destination vector (also referred to as a vector donor and recipient plasmid molecule) as one of two parental RNA molecules comprising one or more nucleic acid segments (pars. 0172, 0198). Bennett, et al. teaches a segment may comprise one or more regions of the adenoviral genome, e.g., left ITR, right ITR, packaging signal, E1, E2, E3, E4, and/or one or more late regions (par. 0305); as evidenced by Danthinne and Imperiale, the adenovirus genome comprises five late regions: L1, L2, L3, L4, and L5 (Fig. 1). Thus, Bennett, et al. implicitly discloses embodiments wherein:
a circular destination vector comprises a segment comprising an E2 region, an L1 region, and an L2 region (par. 0305), which reads on the hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L2 module limitation recited in claim 1;
a circular destination vector comprising a segment comprising an L3 region, and an L4 region (par. 0305), which reads on the hybridization competent adenoviral destination vector backbone comprising a core module comprising an L3-L4 module limitation recited in claim 1;
a circular destination vector comprises a first segment comprising an E2 region, an L1 region, and an L2 region; and a second segment comprising an L3 region and an L4 region (par. 0305), which reads on the hybridization competent adenoviral destination vector backbone comprising a core module comprising both an E2-L2 module and an L3-L4 module limitation recited in claim 1, as well as the wherein the core module comprises an E2-L2 module and an L3-L4 module limitation recited in claim 7; and
a circular destination vector comprises a first segment comprising an E2 region, an L1 region, an L2 region, an L3 region, and an L4 region (par. 0305), which reads on the hybridization competent adenoviral destination vector backbone comprising a core module comprising an E2-L4 module limitation recited in claim 1, as well as the wherein the core module comprises an E2-L4 module limitation recited in claim 8.
Further, Danthinne and Imperiale evidences the adenovirus genome is 36 kb (pg. 1707; col. 1, par. 2); the E1, E3, and E4 regions are 3.2 kb, 3.1 kb, and 2.8 kb, respectively (Fig. 1). Therefore, the embodiments of the destination vector set forth above which lack the E1, E3, and E4 regions (i.e., the E2-L2 module, both the E2-L2 module and L3-L4 module, the E2-L4 module) would be ~26.9 kb; this reads on the wherein the core module is at least 12 kb in length limitation recited in claim 1, as well as the wherein the core module is at least 14 kb in length limitation recited in claim 6.
Bennett, et al. also teaches a circular insert donor (also referred to as an entry clone) as one of two parental RNA molecules comprising one or more nucleic acid segments (par. 0159); further disclosed is a method wherein sequences of interest in the insert donor/entry clone are transferred to the destination vector backbone via recombination reaction (par. 0419). The insert donor/entry clone reads on the hybridization competent adenoviral gene modules limitation recited in claim 1. The method comprising transfer of sequences in the insert donor/entry clone to the destination vector backbone reads on the combining a hybridization competent adenoviral destination vector backbone with one or more hybridization competent adenoviral gene modules limitation recited in claim 1. Bennett, et al. teaches a segment may comprise one or more regions of the adenoviral genome, e.g., left ITR, right ITR, packaging signal, E1, E2, E3, E4, and/or one or more late regions (par. 0305); thus, Bennett, et al. implicitly discloses embodiments wherein:
a circular insert donor/entry clone comprises a segment comprising an E1 region, which reads on the wherein the one or more hybridization competent adenoviral gene modules comprise an E1 module limitation recited in claim 1;
a circular insert donor/entry clone comprises a segment comprising an E3 region, which reads on the wherein the one or more hybridization competent adenoviral gene modules comprise an E3 module limitation recited in claim 1; and
a circular insert donor/entry clone comprises a segment comprising an E4 region, which reads on the wherein the one or more hybridization competent adenoviral gene modules comprise an E4 module limitation recited in claim 1.
Bennett, et al. teaches an embodiment wherein the circular nucleic acid molecules (i.e., the circular destination vector and circular insert donor/entry clone) are digested with endonucleases to produce linear molecules (par. 0029); this reads on the contacting adenoviral gene modules that are circular or contained within a circular plasmid with an endonuclease to form linear adenoviral gene modules limitation recited in claim 1, as well as the contacting a circular destination vector backbone with an endonuclease to form a linear destination vector backbone limitations recited in claim 12.
Bennett, et al. does not teach the remaining limitations recited in claims 1 and 12.
However, Elledge teaches sequence and ligation independent cloning (Title), a method of generating recombinant DNA by homologous recombination without the use of ligases, comprising an initial step of amplifying one or more target DNA molecules by PCR using forward and reverse primers, each typically 15-100 (and more typically 15-50) nucleotides in length, wherein the forward primer terminates at one end in sequence A and the reverse primer terminates at one end in sequence B, both 15-100 (and more typically 15-50) nucleotides in length (par. 0007). The second step comprises a single-stranded terminal region, typically 15-100 nucleotides long, generated in the amplified DNA molecules using exonuclease digestion so that, at one end, they have a 5' overhang corresponding to sequence A and, at the other end, a 5' overhang corresponding to sequence B (par. 0007). These fragments are then annealed with a linearized vector that terminates at each end with a single-stranded region (again, typically 15-100 and more typically 15-50 nucleotides long), wherein one end has a sequence C exactly complementary to sequence A, and the other end has a sequence D, exactly complementary to sequence B (par. 0007). Once annealing is complete, a host cell is transformed with the annealed complexes that have been formed (par. 0007). SLIC mimics in vivo homologous recombination by relying on exonuclease generation of single-stranded DNA overhangs on insert and vector fragments and the assembly of these fragments by recombination in vitro (par. 0048); SLIC can be used to assemble DNA made by PCR or restriction fragments, wherein the only requirement is fragments to be assembled contain, on their ends, sequences of 20 bp or longer to allow stable annealing, i.e., overhangs (par. 0089).
It would have been prima facie obvious to a person having ordinary skill in the art to have used the homologous recombination technique SLIC, as taught by Elledge, in the method to construct a modular viral vector taught by Bennett, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would have been motivated to use the homologous recombination technique SLIC instead of site-specific recombination as SLIC does not require specific sequences (par. 0006), and facilitates initial assembly of the gene of interest into the origin plasmid without the use of expensive enzymes required for initial cloning (par. 0005). This modification results in a method which reads on:
the sequence and ligation independent cloning (SLIC) limitation recited in claim 1;
the wherein the hybridization competent adenoviral gene modules are each linear and each comprise a single-stranded nucleic acid overhang of about 20 to about 25 base pairs in length limitation recited in claim 1;
the contacting the linear adenoviral gene modules with an exonuclease to form the one or more hybridization competent adenoviral gene modules limitations recited in claim 1;
the wherein the hybridization competent destination vector backbone and the one or more hybridization competent adenoviral gene modules each comprise a single-stranded nucleic acid overhang on each terminus limitation recited in claim 10; and
the contacting the linear destination vector backbone with an exonuclease to form the hybridization competent destination vector backbone limitation recited in claim 12.
Further, Gibson, et al. teaches SLIC methods, referred to as chew-back and anneal (CBA) and T4 polymerase fill-in, efficiently and similarly assembled cassettes 66-69 and a bacteria artificial chromosome (BAC) vector (i.e., five DNA fragments) into a plasmid clone ~31kb in size (‘Supplementary Results: Comparison of 5 DNA Assembly Methods’, Supplementary pg. 11; Fig. 5a-b). As Bennett, et al. teaches wild-type adenoviruses have a 36 kb genome (par. 0006), a person having ordinary skill in the art would have a reasonable expectation of success using the homologous recombination technique SLIC, as taught by Elledge, in the method to construct a modular viral vector taught by Bennett, et al.
This renders obvious the limitations recited in claims 1, 6-8, 10, and 12.
Regarding claim 13: Following the above discussion, Bennett, et al. teaches the linear viral vector may be introduced into an appropriate host cell, e.g., by transfection (par. 0321); this reads on the transfecting the adenovirus genome into a cell limitation recited in claim 13.
Regarding claim 14: Following the above discussion, Bennett, et al. teaches after joining the segments, the product molecule will contain at least sufficient viral sequences to permit the packaging of the product molecule in a viral particle (par. 0217); the product molecule containing sufficient viral sequences to permit the packaging of said molecule in a viral particle comprising all of an adenoviral genome necessarily is capable of forming a recombinant adenovirus, and thus reads on the wherein the adenovirus genome is capable of forming a recombinant adenovirus when expressed in a cell limitation recited in claim 14.
Regarding claim 15: Following the above discussion, Bennett, et al. teaches it is not necessary that all viral functions required for replication be contained on a segment and be included in the final nucleic acid molecule comprising a portion of the viral genome (par. 0319); viruses lacking a particular function could be prepared in a cell line expressing the particular function (par. 0320). The nucleic acid molecule comprising a portion of the viral genome lacking a particular function and prepared in a cell line expressing the particular function reads on the wherein the adenovirus genome is a partial adenovirus genome construct that is capable of forming a recombinant adenovirus when expressed in a complementing cell line limitation recited in claim 15.
Regarding claim 16: Following the above discussion, Bennett, et al. teaches the viral genome may be wild-type or contain one or more mutations, insertions, and/or deletions, further disclosing an embodiment wherein adenoviral genomes contain one or more deletions, e.g., E1 and E3 regions (par. 0025). An adenoviral genome lacking the E1 and E3 regions reads on the wherein at least one of the one or more hybridization competent adenoviral gene modules comprises one or more modifications relative to the wild type adenovirus from which the gene module is derived limitation recited in claim 16.
Claim 3 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bennett, et al. (US 2004/0219516), in view of Elledge (US 2007/0292954) and Gibson, et al. (Nat Methods. 2009), further in view of McVey, et al. (US 2003/0170899); as evidenced by Danthinne and Imperiale (Gene Ther. 2000).
The teachings of Bennett, et al., Elledge, and Gibson, et al. are set forth above.
McVey, et al. teaches a method of making eukaryotic gene transfer vectors (Abstract).
Regarding claim 3: It is set forth above the modified method of Bennett, et al. renders obvious the method of claim 1. The modified method does not teach the hybridization competent destination vector backbone as comprising a p15A origin of replication, as required by the limitation recited in the instant claim.
However, McVey, et al. teaches vector stability is enhanced by low copy number, non-phage origins of replication, e.g., p15A (par. 0045), further disclosing low copy number origins of replication help to maintain the integrity of large, autonomously-replicating DNAs (par. 0150); this reads on the p15A limitation recited in claim 3.
It would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Bennett, et al. by including a p15A origin of replication in the hybridization competent destination vector backbone, as taught by McVey, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would be motivated to do so to enhance vector stability and maintain the integrity of large, autonomously-replicating DNAs, as taught by McVey, et al. Further, a person skilled in the art would have more than a reasonable expectation of success, as Bennett, et al. teaches the nucleic acid molecules of the same disclosure may further comprise origins of replication (par. 0023).
This renders obvious the limitations recited in claim 3.
Claim 4 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bennett, et al. (US 2004/0219516) in view of Elledge (US 2007/0292954) and Gibson, et al. (Nat Methods. 2009), further in view of Gao, et al. (Gene Ther. 2003), as evidenced by Danthinne and Imperiale (Gene Ther. 2000).
The teachings of Bennett, et al., Elledge, and Gibson, et al. are set forth above.
Gao, et al. teaches a method for the high throughput creation of adenovirus vectors (Abstract).
Regarding claim 4: It is set forth above the modified method of Bennett, et al. renders obvious the method of claim 1. The modified method does not teach the hybridization competent destination vector backbone as comprising a mammalian I-SceI expression cassette, as required by the limitation recited in the instant claim.
However, Gao, et al. teaches specificity and effectiveness of I-SceI-mediated cleavage for releasing an adenoviral vector genome from a circular plasmid in a cell after transfection, disclosing I-SceI recognition sites were engineered into the vector plasmid outside the ITRs of adenovirus genomes in circular plasmids, which were transfected into 293 cells expressing I-SceI endonuclease, leading to efficient release of the adenovirus linear genome (pg. 1927; col. 1, par. 2); this reads on the mammalian I-SceI expression cassette limitation recited in claim 4.
It would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Bennett, et al. by including a mammalian I-SceI expression cassette in the hybridization competent destination vector backbone, as taught by Gao, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would be motivated to do so for the specificity and effectiveness of I-SceI-mediated cleavage leading to the efficient release of an adenovirus linear genome taught by Gao, et al. Further, one skilled in the art would have more than a reasonable expectation of success, as Gao, et al. teaches the use of I-SceI-mediated cleavage in the context of adenoviral vector genomes.
This renders obvious the limitations recited in claim 4.
Maintained/Modified Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-4, 6-8, 10, and 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,217,160.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1: Claim 1 of U.S. Patent No. 9,217,160 (hereinafter Patent ‘160) recites a method of making a recombinant adenovirus, comprising:
assembling an adenoviral core module destination vector by combining a hybridization competent vector back bone with one or more hybridization competent adenoviral gene modules by sequence and ligation independent cloning (SLIC), wherein the one or more hybridization competent adenoviral gene modules form a core module that comprises an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, or an E2-L4 module, wherein the core module is at least 12 kb in length;
inserting into the adenoviral core module destination vector recombination site nucleic acid sequences that flank the core module, thereby forming a recombination competent core module destination vector; and
assembling an adenovirus genome by combining the recombination competent core module destination vector with one or more recombination competent adenoviral gene modules by site-specific recombination, wherein the one or more recombination competent adenoviral gene modules comprise an E1 module, an E3 module, an E4 module, or any combination thereof.
Claim 7 of Patent ‘160 recites wherein the hybridization competent vector backbone and the one or more hybridization competent adenoviral gene modules comprise a single-stranded nucleic acid overhang of about 20 to about 25 base pairs in length.
Claim 9 of Patent ‘160 recites wherein the one or more hybridization competent adenoviral gene modules are formed by:
contacting adenoviral gene modules that are circular or contained within a circular plasmid with an endonuclease to form linear adenoviral gene modules; and
contacting the linear adenoviral gene modules with an exonuclease to form the one or more hybridization competent adenoviral gene modules.
Claims 1, 7, and 9 of Patent ‘160 anticipates the limitations of instant claim 1.
Regarding claim 3: Claim 2 of Patent ‘160 recites wherein the hybridization competent vector backbone comprises a p15A origin of replication; this anticipates the limitations recited in instant claim 3.
Regarding claim 4: Claim 3 of Patent ‘160 recites wherein the hybridization competent vector backbone comprises a mammalian I-SceI expression cassette; this anticipates the limitations recited in instant claim 4.
Regarding claim 6: Claim 4 of Patent ‘160 recites wherein the core module is at least 14 kb in length; this anticipates the limitations recited in instant claim 6.
Regarding claim 7: Claim 5 of Patent ‘160 recites wherein the core module comprises an E2-L2 module and an L3-L4 module; this anticipates the limitations recited in instant claim 7.
Regarding claim 8: Claim 6 of Patent ‘160 recites wherein the core module comprises an E2-L4 module; this anticipates the limitations recited in instant claim 8.
Regarding claim 10: Claim 8 of Patent ‘160 recites wherein the hybridization competent vector backbone and the one or more hybridization competent adenoviral gene modules comprise a single-stranded nucleic acid overhang on each terminus; this anticipates the limitations recited in instant claim 10.
Regarding claim 12: Claim 10 of Patent ‘160 recites wherein the hybridization competent vector backbone is formed by:
contacting a circular vector backbone with an endonuclease to form a linear vector backbone; and
contacting the linear vector backbone with an exonuclease to form the hybridization competent vector backbone.
This anticipates the limitations recited in instant claim 12.
Regarding claim 13: Claim 14 of Patent ‘160 recites the method of claim 1 as further comprising transfecting the adenovirus genome into a cell; this anticipates the limitations recited in instant claim 13.
Regarding claim 14: Claim 15 of Patent ‘160 recites wherein the adenovirus genome is capable of forming a recombinant adenovirus when expressed in a cell; this anticipates the limitations recited in instant claim 14.
Regarding claim 15: Claim 16 of Patent ‘160 recites wherein the adenovirus genome is a partial adenovirus genome construct that is capable of forming a recombinant adenovirus when expressed in a complementing cell line or when expressed in a cell with a helper virus; this anticipates the limitations recited in instant claim 15.
Regarding claim 16: Claim 17 of Patent ‘160 recites wherein at least one of the one or more recombination competent or hybridization competent adenoviral gene modules comprises one or more modifications relative to the wild type adenovirus from which the gene module is derived; this anticipates the limitations recited in instant claim 16.
Claims 1-16 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,577,589.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1, 12, 14: Claim 1 of U.S. Patent No. 10,577,589 (hereinafter Patent ‘589) recites a method of making a recombinant adenovirus, comprising:
(i) assembling an adenoviral core module destination vector by combining a hybridization competent vector backbone with one or more hybridization competent adenoviral gene modules by sequence and ligation independent cloning (SLIC), wherein the one or more hybridization competent adenoviral gene modules form a core module that is at least 12 kb in length and the gene modules are selected from the group consisting of an E2-L2 module, an L3-L4 module, both an E2-L2 module and an L3-L4 module, and an E2-L4 module, wherein the E2-L2 module comprises adenovirus E2B, L1 and L2 regions, the L3-L4 module comprises adenovirus L3, E2A and L4 regions, and the E2-L4 module comprises adenovirus E2B, L1, L2, L3, E2A and L4 regions;
(ii) contacting the adenoviral core module destination vector with an endonuclease to form a linear core module destination vector;
(iii) contacting the linear core module destination vector with an exonuclease to form a hybridization competent core module destination vector, wherein the hybridization competent core module destination vector comprises a mammalian I-SceI expression cassette; and
(iv) assembling an adenovirus genome that is at least 24 k kb in length by contacting the hybridization competent core module destination vector with one or more hybridization competent gene modules, wherein the one or more hybridization competent adenoviral gene modules are selected from the group consisting of an E1 module, an E3 module, and an E4 module, and wherein the E1 module comprises an adenovirus E1A region, an adenovirus E1B region, or both adenovirus E1A and E1B regions, the E3 module comprises adenovirus E3 and L5 regions, and the E4 module comprises an adenovirus E4 region, thereby making a recombinant adenovirus.
Claim 6 of Patent ‘589 recites wherein the hybridization competent core module destination vector and the one or more hybridization competent adenoviral gene modules comprise a single-stranded nucleic acid overhang of about 20 to about 25 bases in length.
Claim 8 of Patent ‘589 recites the method of claim 1 as further comprising generating the one or more hybridization competent adenoviral gene modules of step (i) or step (iv), or both step (i) and step (iv), by:
contacting circular adenoviral gene modules or adenoviral gene modules contained within a circular plasmid with an endonuclease, thereby forming linear adenoviral gene modules; and
contacting the linear adenoviral gene modules with an exonuclease, thereby forming the one or more hybridization competent adenoviral gene modules.
Claims 1, 6, and 8 of Patent ‘589 anticipate the limitations recited in instant claims 1, 12, and 14.
Regarding claim 3: Claim 2 of Patent ‘589 recites wherein the hybridization competent core module destination vector comprises a p15A origin of replication; this anticipates the limitations recited in instant claim 3.
Regarding claim 6: Claim 3 of Patent ‘589 recites wherein the core module is at least 14 kb in length; this anticipates the limitations recited in instant claim 6.
Regarding claim 7: Claim 4 of Patent ‘589 recites wherein the core module consists of an E2-L2 module and an L3-L4 module; this anticipates the limitations recited in instant claim 7.
Regarding claim 8: Claim 5 of Patent ‘589 recites wherein the core module consists of an E2-L4 module; this anticipates the limitations recited in instant claim 8.
Regarding claim 10: Claim 7 of Patent ‘589 recites wherein the hybridization competent core module destination vector and the one or more hybridization competent adenoviral gene modules comprise a single-stranded nucleic acid overhang on each terminus; this anticipates the limitations recited in instant claim 10.
Regarding claim 13: Claim 9 of Patent ‘589 recites the method of claim 1 as further comprising transfecting the adenovirus genome into a cell; this anticipates the limitations recited in instant claim 13.
Regarding claim 14: Claim 10 of Patent ‘589 recites wherein the adenovirus genome is capable of forming a recombinant adenovirus when expressed in a cell; this anticipates the limitations recited in instant claim 14.
Regarding claim 15: Claim 11 of Patent ‘589 recites wherein the adenovirus genome is a partial adenovirus genome construct that is capable of forming a recombinant adenovirus when expressed in a complementing cell line or when expressed in a cell with a helper virus; this anticipates the limitations recited in instant claim 15.
Regarding claim 16: Claim 12 of Patent ‘589 recites wherein at least one of the one or more hybridization competent adenoviral gene modules comprises one or more modifications relative to the wild type adenovirus from which the gene module is derived; this anticipates the limitations recited in instant claim 16.
Conclusion
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 GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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, CHRISTOPHER BABIC can be reached at (571)272-8507. 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.
/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
Prosecution Insights