DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments to the claims and argument filed December 18, 2026 have been received and entered. Claims 1-39, 56-68 have been canceled, while claim 40 has been amended. The objection to claim 40 is withdrawn in view of applicant’s amendments to the claim. It is noted that status identifier for claims 51-55 is incorrect and should be corrected as withdrawn claims in response to this office action. Claims 40-55 are pending in the instant application.
Priority
This application is a continuation of US application no 17830011 filed on June 1, 2022 which is a continuation of US application no 17/590,613 filed on 02/01/2022, which is a continuation of 17/366,290 filed on 07/02/2021, which is a continuation of 16/800,444 filed on 02/25/2020, which is a continuation of 16/601,144 filed on 10/14/2019, which claims priority from US provisional 62/864,432 filed on 06/20/2019, US provisional 62/830,654 filed on 04/08/2019, US provisional of 62/746,497 filed on 10/16/2018.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/18/2025. and 02/28/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant’s election of claims 46-50, 59-63 (group I) in the reply filed on April 4, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 40-45, 56-58 link the invention of group I. It is noted that previous office action inadvertently included claim 68 as part of linking claim, however, claim 68 that is dependent upon claim 64 should be included in group II. Therefore, claim 68 is included in group II. Applicant’s election of AAV as species of viral vector for claim was acknowledged. However, upon further consideration election of species requirement between different species of viral vector was withdrawn.
Claims 51-55 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 26, 2025.
Claims 40-50 are under consideration.
New-Claim Rejections - 35 USC § 112- necessitated by amendments
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 40-50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, the recitation of limitation producing an AAV particle from said plasmid ( a comprising an ITR flaking said transgene) ” (claim 40) is considered new matter. Applicants point that the amendments are fully supported by the specification and common knowledge in the art. However, upon further review of the instant specification, examiner could not find support for step of producing AAV particle from said plasmid as required by the claim nor does instant specification teaches the step incorporated by any reference. There is no explicit or implicit support for using this essential method step. In fact, contrary to applicants' assertions, instant specification directly supports to a transgene that could be designed to be 4.7 kb or less and incorporated into AAV vector or virus particle (see page 34, lines 1-2 of the specification). The specification fails to disclose this essential subject matter as recited in the claim. It is emphasized that indicated support at best is directly to a product claim. Thus, at the time the application was filed, an Artisan of skill would not recognize from the disclosure that Applicant was in possession of a method of making AAV as required by the claim 40. In case if applicants have evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for the method steps as recited in claim 40 of the instant application.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph-written description requirement”. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981). Claims 41-50 are included in the rejection because they directly or indirectly depend from the rejected base claim. This is a new matter rejection.
Maintained-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 40-50, 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 40-50 remain rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The claims 40 and 56 as written reads on incorporating transgene randomly without reciting any specific step as to how transgene is incorporated in an AAV particle or any viral particle. It is known in prior art that method of making viral vector is controlled to ensure efficient packaging and gene delivery involves cloning transgene into AAV vector plasmid between AAV ITRs that are crucial for genome replication and packaging as evident from the teaching of Mueller et al (Curr Protoc Microbiol. 2012 August; 0 14: 1-24). The method generally involves transfection of AAV plasmid containing the transgene, packaging plasmid, and helper plasmid into packaging cells such as HEK293 cells to produce AAV/virus particle that are then purified to thereby produce AAV vector comprising the transgene. Claims 41-50, 57-62 and 63 are included in the rejection because they directly or indirectly depend from the rejected base claim. Appropriate correction and/or amendment is required.
Response to arguments
Applicant disagree with the rejection arguing one of ordinary skill in the art routinely knows the steps for making a viral particle and they typically do not need to be recited in the art in any detail. Applicants’ arguments have been fully considered, but are not found persuasive.
In response it is noted that instant method claims omit essential method step as claimed. Specifically, instant specification prophetically contemplates a transgene that could be designed to be 4.7kh or less, and incorporated into an AAV vector and particle (see page 34, lines 1-2). The claimed method fails to limit the size of the transgene that could be incorporated into AAV vector or virus particle. Further, the ITR flanked particle could only be replicated and packaged only in presence of Rep/Cap and helper function. The specification further fails to incorporate missing essential steps and/or elements incorporated by references. In view of foregoing, it is apparent that method as claimed omits essential elements and/or method step to produce the AAV particle as required by the claim.
Withdrawn -Claim Rejections - 35 USC § 103
Claims 40-50, 56-62, and 63 were rejected under 35 U.S.C. 103 as being unpatentable over Ohmori et al (Scientific Reports, 2017, 7, 4159, 1-11, IDS), Jaskula-Ranga et al (WO/2018/009534, EFD07/5/2016, IDS), Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018) and Harrington et al (US6740503), Sheng et al (Canadian Journal of Microbiology, 2014, 445-454, IDS) /Ryu et al (Plant Molecular Biology 54: 489-502, 2004, IDS)/Jarvis (US 2020/0231974, 7/23/2020, IDS) . Applicant’s amendments to the claims and arguments are found persuasive, therefore, previous rejection of claim is hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot.
Maintained-Double Patenting
Claims 40-50, remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, of USP.12054706 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in 12054706 is directed to a vector comprising a transgene comprising from 5′ to 3′ orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous Factor VIII gene, and wherein the transgene is equal to or less than 4.7 kb. Dependent claims limit the vector is a viral vector selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector subsequently limiting to an adeno-associated viral vector. The method of instant application produces a viral vector that is encompassed by the viral vector embraced by the breadth of claims in 706. Therefore, method of making AAV vector or viral vector that is encompassed by claims in ‘706.
Claims 40-50, remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No.11091756 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in 11091756 is directed to a method that use a transgene comprising in 5′ to 3′ orientation a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement; or a first splice acceptor, a first coding sequence, a bidirectional terminator, a second coding sequence reverse complement, and a second splice acceptor reverse complement; wherein the first recombinant nucleic acid comprises a transgene comprising in 5′ to 3′ orientation a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement. Dependent claim 3 limits the transgene wherein the first recombinant nucleic acid comprises a transgene comprising in 5′ to 3′ orientation a first splice acceptor, a first coding sequence, a bidirectional terminator, a second coding sequence reverse complement, and a second splice acceptor reverse complement. The method further limits the transgene is integrated into an intron 9 of the ATXN3 gene (claim 4-5). Claims 8-10 limit the transgene that is harbored on a viral vector, wherein the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector and, wherein the transgene is equal to or less than 4.7 kb in length. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; gene of interest (ATXN3), and wherein the transgene is equal to or less than 4.7 kb) are taught by ‘756. The method of ‘756 uses a transgene that is harbored on a viral vector, wherein viral vector is elected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector. Therefore, the method of 756 encompass the AAV vector or viral vector produced by the method claimed in the instant application.
Claims 40-50 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, of USP. 11993770 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in ‘770 are directed to recombinant nucleic acid comprising, (i) a transgene, the transgene comprising from 5′ to 3′ orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous gene, and wherein the transgene is equal to or less than 4.7 kb, and (ii) adeno-associated virus inverted terminal repeats flanking the transgene, and wherein the recombinant nucleic acid is in a circular conformation. Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; a gene, and wherein the transgene is equal to or less than 4.7 kb) are taught by ‘770 and further they are taught in various combinations and are shown to be used as therapeutic nucleic acid. It would be therefore predictably obvious to incorporate the transgene comprising the combination of these elements into a virus particle to make AAV or viral vector using method known and disclosed in Carlo (see para.578, 619-621). Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘770 with Carlo by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making encompass the nucleic acid of ‘770.
Claims 40-50 remain are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11365407 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in 11365407 is directed to a transgene comprising from 5′ to 3′ orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous Factor IX gene, and wherein the transgene is equal to or less than 4.7 kb. Dependent claim limit terminator is selected from an SV40 poly(A) or BGH poly(A). Claim 6 limits the transgene is harbored on a viral vector. In the instant case, each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; a coding seqeunce (FIX), and wherein the transgene is equal to or less than 4.7 kb) are taught by ‘407 and further they are taught in various combinations and are shown to be used as nucleic acid. The 407 differs from claimed invention by not disclosing incorporating the transgene into a virus or AAV particle to make AAV or viral vector. It would be therefore predictably obvious to incorporate the transgene comprising the combination of these elements into a virus or AAV particle to make AAV or viral vector using method known and disclosed in Carlo (see para. 578, 619-621). Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘407 with Carlo by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making encompass the nucleic acid of ‘407.
Claims 40-50 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No.11254930 in view Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in 11254930 is directed to a recombinant nucleic acid comprising a transgene, the transgene comprising in 5′ to 3′ orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence encodes an amino acid sequence, and the second coding sequence encodes the same amino acid sequence as the first coding sequence, wherein the first coding sequence and second coding sequence comprise different polynucleotide sequences, but each encodes the same amino acid sequence. Claims 3and 4 are directed to a recombinant non-viral vector comprising the recombinant nucleic acid of claim 1 or viral vector comprising the recombinant nucleic acid of claim 1. Subsequently limiting to the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector. Claim 9 limit the recombinant nucleic acid is equal to or less than 4.7 kb. Claims 10-12 recite the same transgene as claim 1 within cells. Claims in ‘930 differs from claimed invention by not disclosing (i) coding sequence is a reporter gene or a tag. Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; a gene, and wherein the transgene is equal to or less than 4.7 kb) are taught by ‘930 and further they are taught in various combinations and are shown to be used as AAV or viral vector. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘930 with Carlo (see para. 578, 619-621) by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making encompass the recombinant nucleic acid comprising a transgene of ‘407.
Claims 40-50 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-39, of copending Application No.18526794 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in ‘794 are directed to a transgene comprising from 5' to 3' orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences are amino acids encoded by the corresponding endogenous gene for acid maltase deficiency, and wherein the transgene is equal to or less than 4.7 kb. , wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A). Claims 23-27 limit the transgene that is harbored on a viral vector, wherein the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector, subsequently limiting to an adeno-associated viral vector and wherein the transgene does not comprise homology arms. Claims 29, 34-39 are directed to an adeno-associated viral vector comprising:(i) a transgene comprising from 5' to 3' orientation a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous gene, and wherein the transgene is equal to or less than 4.7 kb; and (ii) adeno-associated virus inverted terminal repeats flanking the transgene, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A), and wherein the transgene does not comprise homology arms (claim 37). Claims in ‘794 differs from claimed invention by not disclosing (i) coding sequence is reporter gene or a tag. However, before the effective filing date, regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; gene of interest, are taught by ‘407. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘930 with Carlo (see para. 578, 619-621) by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making encompass the recombinant nucleic acid comprising a transgene of ‘407.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 40-50 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-39, of copending Application No.18526772 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast claims in ‘772 are directed to a transgene comprising from 5' to 3' orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences are amino acids encoded by the corresponding endogenous gene for alpha-1 antitrypsin deficiency, and wherein the transgene is equal to or less than 4.7 kb and, wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A). Claims 23-27 limit the transgene that is harbored on a viral vector, wherein the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector, subsequently limiting to an adeno-associated viral vector and wherein the transgene does not comprise homology arms. Claims 29, 34-37, 39 are directed to an adeno-associated viral vector comprising:(i) a transgene comprising from 5' to 3' orientation a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous gene, and wherein the transgene is equal to or less than 4.7 kb; and (ii) adeno-associated virus inverted terminal repeats flanking the transgene, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A). Claims in ‘772 differs from claimed invention by not disclosing (i) coding sequence is reporter gene or a tag.. However, before the effective filing date, regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; gene of interest, are taught by ‘772. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘772 with Carlo (see para. 578, 619-621) by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making encompass the recombinant nucleic acid comprising a transgene of ‘772.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 40-50 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-39, of copending Application No.18526758 and Carlo et al (US20200040362, dated 02/06/2020, EFD, 06/28/2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in ‘758 are directed to a transgene comprising from 5' to 3' orientation: a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first terminator is selected from an SV40 poly(A) or BGH poly(A), wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences are amino acids encoded by the corresponding endogenous gene for ATXN3 gene, and wherein the transgene is equal to or less than 4.7 kb and, wherein the second terminator is selected from an SV40 poly(A) or BGH poly(A). Claims 20-27 limit the transgene that is ATXN3 harbored on a viral vector, wherein the viral vector is selected from the group consisting of an adenovirus vector, an adeno-associated virus vector, and a lentivirus vector, subsequently limiting to an adeno-associated viral vector. Claims 29-39 are directed to an adeno-associated viral vector comprising:(i) a transgene comprising from 5' to 3' orientation a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, and the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein the first and second coding sequences differ in nucleic acid sequence but encode the same amino acids, wherein said amino acids encoded by the first and second coding sequences correspond to amino acids encoded by an endogenous gene, and wherein the transgene is equal to or less than 4.7 kb; and (ii) adeno-associated virus inverted terminal repeats flanking the transgene. Claims in ‘758 differs from claimed invention by not disclosing (i) coding sequence is reporter gene or a tag. Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (two cassettes having splice acceptor, coding sequence and terminators in reverse orientations to each other; gene of interest, are taught by ‘758. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘758 with Carlo (see para. 578, 619-621) by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making viral or AAV vector encompass the recombinant nucleic acid comprising a transgene of ‘758. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 40-50 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18, 24-26, of copending Application No.18526826.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to similar nucleic acid transgene configuration. For instance, in the instant case, claims are directed to method for making an adeno-associated vectors (AAV) vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into an AAV particle, thereby making said AAV vector comprising said transgene. Dependent claims limit said AAV vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh.10 vector, subsequently limiting AAV vector to an AAV8 vector. Claims 47-49 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. Claims are also directed to a method for making a vector comprising a transgene, wherein said transgene comprises, from 5' to 3' orientation:(a) a first splice acceptor, a first coding sequence, a first terminator, a second terminator reverse complement, a second coding sequence reverse complement, and a second splice acceptor reverse complement, wherein the first coding sequence is operably linked to the first splice acceptor and first terminator, wherein the second coding sequence is operably linked to the second splice acceptor and second terminator, wherein said method comprises incorporating said transgene into a viral particle, thereby making said vector comprising said transgene. Dependent claims limit the said vector is an adenovirus vector, an AAV vector, or a lentivirus vector or id vector is a retroviral vector, a herpes simplex virus vector, a pox virus vector, or an Epstein bar virus vector. Claims 60-63 limit the first coding sequence of (a) and said second coding sequence of (a) encode GFP, luciferase, or epitope tag subsequently limiting to epitope tag is a Strep-tag, a Myc-tag, an AviTag, or an HA-tag. In contrast, claims in in ‘826 are directed to An isolated genetically modified eukaryotic cell comprising a transgenewherein the first and second coding sequences differ in nucleic acid sequence but each encode the same amino acid sequence, wherein said amino sequences encoded by the first and second coding sequences encodes prima facie obvious for a person of ordinary skill in the art to combine the teachings to modify the transgene of ‘826 with Carlo (see para. 578, 619-621) by incorporating transgene into viral particle to make viral vector for integrating the transgene into cell. Therefore, the method of making viral or AAV vector encompass the recombinant nucleic acid comprising a transgene of ‘826. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant fails to rebut the rejection of record and therefore, obviousness type double patenting rejection is maintained for the reasons of record.
Conclusion
No claims allowed.
Examiner’s note: Applicant should note that Applicant's arguments and reliance on arguments filed during the prosecution of the prior applications that relied in part on declaration filed under 37 CFR 1.130, 1.131 and 1.132,do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application (see MPEP 201.06(c) IX).
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Finn (US 20200270617, EFD 10/18/2018) teaches a nucleic acid construct is a bidirectional nucleic acid construct. In some embodiments, the construct comprises: i. a first segment comprising a coding sequence for a heterologous polypeptide; and ii. a second segment comprising a reverse complement of a coding sequence of the heterologous polypeptide. In some embodiments, the construct comprises a polyadenylation signal sequence. In some embodiments, the construct comprises a splice acceptor site. In some embodiments, the construct does not comprise a homology arm (see para. 12, Fig. 1-5). Finn is not applied as prior art as effective filing date of Finn is 2 days after the EFD of instant application.
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.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632