DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of an expression cassette comprising a polynucleotide sequence encoding GLUT1, operatively linked to a promoter (invention of Group I), and of the species of an FLT-1 promoter of SEQ ID NO:1 (Species Group A, promoter sequences) and of an expression cassette of SEQ ID NO:12 (Species Group B, expression cassette sequences) in the reply filed on 12/14/2025 is acknowledged. However, the species election requirement of Species Group A (drawn to promoter sequences) and Species Group B (drawn to expression cassette sequences) are withdrawn.
Claims 28-29, 31-32, 34-37, 42-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/14/2025.
Claims Status
Claims 4-14, 16-20, 25-27, 30, 33, 38-41 is/are cancelled. Claims 1-3, 15, 21-24, 28-29, 31-32, 34-37, 42-45 is/are currently pending with claims 28-29, 31-32, 34-37, 42-43 withdrawn. Claims 1-3, 15, 21-24, 44-45 is/are under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
112(b):
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 22, 24 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.
Claim 24 recites rAAV capsid proteins of SEQ ID NOs:15-17. Claim 22 recites an expression cassette of SEQ ID NOs:9, 11, 13, 15. However, in the current sequence listing, SEQ ID NOs:9, 11, 13, and 15 do not exist (see image below of SEQ ID NO:15 as an example), and SEQ ID NOs:16-17 are polynucleotide sequences, not polypeptide sequences, with the descriptors “Made in Lab – part of expression cassette” (SEQ ID NO:16) and “Made in Lab – full polynucleotide sequence of vector genome” (SEQ ID NO:17). A polynucleotide sequence is not a protein sequence, and thus SEQ ID NOs:15-17 cannot be rAAV capsid proteins, as recited in claim 24. Furthermore, SEQ ID NOs:15-16 are described in claim 22 as being expression cassette sequences. It is unclear what sequence(s) of viral capsid proteins are recited by claim 24; moreover, the lack of defined sequences associated with SEQ ID NOs:9, 11, 13, and 15 renders the metes and bounds of claims 22 and 24 unclear. Thus, claims 22 and 24 are rendered indefinite. The optional limitation of claim 24 that the rAAV vector comprises a capsid protein at least 90% identical to SEQ ID NOs:15-17 thus cannot be further examined. However, the required limitation of claim 24 (that the gene therapy vector is an rAAV vector) and the other optional limitation of claim 24 (regarding the serotype of the rAAV vector) do not rely on or require the optional limitation regarding an rAAV vector capsid protein sequence, and thus are further examined.
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112(a):
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 1-3, 15, 21-24, 44-45 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.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claim 1 recites a “functional variant” of GLUT1. The specification describes a “functional variant” of a protein as having “one or more amino-acid substitutions, insertions, or deletion compared to a parental protein that retains one or more desired activities of the parental protein” (paragraph [0084]). However, the specification does not describe what the “one or more desired activities” of GLUT1 are, such that a given polypeptide can be considered a “functional variant” of GLUT1. Furthermore, as neither the specification nor claims 1-3, 21-24, and 44-45 describe any sequence or structural limitations of GLUT1 variants, an artisan would not be able to determine the sequence identity to wild-type GLUT1 or the sequence elements required for a given polypeptide to be encompassed by a “variant” of GLUT1. Thus, an artisan would not be able to determine the bounds of the genus of “functional variants” of GLUT1 and would not be able to determine that the applicants were in possession of a number of species representative of the full scope of the genus of “functional variants” of GLUT1.
Claim 3 recites an FLT-1 promoter sequence at least 75% identical to SEQ ID NO:1, a Tie-1 promoter sequence at least 75% identical to SEQ ID NO:2, and a VE-cadherin promoter sequence at least 75% identical to SEQ ID NO:3, creating three enormous genera of promoter sequences, which genera are not sufficiently described. Claim 15 recites a 3’ UTR sequence at least 75% identical to SEQ ID NO:4, and an SLC2A1 polynucleotide sequence at least 75% identical to SEQ ID NO:5, creating an enormous genus of 3’ UTR sequences and an enormous genus of SLC2A1 sequences, wherein neither genera is sufficiently described. Claim 21 recites AAV ITRs at least 75% identical to SEQ ID NOs:6-7, creating an enormous genus of AAV ITR sequences, which are not sufficiently described. Claim 22 recites expression cassettes at least 75% identical to SEQ ID NOs:8-16, 97, 99, and 101, creating an enormous genus of expression cassette sequences which is not sufficiently described.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, SEQ ID NO:1 is the only species of FLT-1 promoter which is disclosed; SEQ ID NO:2 is the only species of Tie-1 promoter which is disclosed; SEQ ID NO:3 is the only species of VE-cadherin promoter which is disclosed; SEQ ID NO:4 is the only species of 3’UTR which is disclosed; SEQ ID NO:5 is the only species of SLC2A1 sequence which is disclosed; SEQ ID NOs:6-7 are the only species of AAV ITR which are disclosed; SEQ ID NOs:8-16, 97, 99, and 101 are the only species of full-length expression cassette sequences which are disclosed. While the genera encompass large numbers of variants and molecules that have the same activity as promoters (SEQ ID NOs:1-3) or AAV ITRs (SEQ ID NOs:6-7) (and no specific function is required of the genus of SLC2A1 variants), and the genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genera of sequences at least 75% identical to SEQ ID NOs:1-16, 97, 99, and 101 or functional equivalents thereof. Additionally, the specification does not describe the complete structure of a representative number of species of the large genera of modified promoters, SLC2A1 sequences, AAV ITRs, 3’UTR sequences, and expression cassette sequences.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that the promoter sequences at least 75% identical to SEQ ID NOs:1-3 have functionality as promoters, that the sequences at least 75% identical to SEQ ID NOs:6-7 have functionality as AAV ITRs, and that the expression cassette sequences encode a “functional variant” of Glut1 and a promoter (wherein the genus of Glut1 “functional variants” and the genus of promoters lack sufficient written description). Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of the genera of promoters, SLC2A1 sequences, 3’UTRs, AAV ITRs, and expression cassettes, or functional equivalent thereof, all members of the claimed genera will have these characteristics. Further, no identifying characteristics of the modified promoters, SLC2A1 sequences, 3’UTRs, AAV ITRs, and expression cassettes are disclosed.
The inventions of claims 2, 23-24, and 44-45 require the use of the inventions of claims 1, 3, 15, 21-22 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim recites an expression cassette comprising a promoter operatively linked to a polynucleotide sequence encoding GLUT1, encompassing the SLC2A1 gene and the Glut1 promoter sequence of a naturally-occurring organism, such as a human. This judicial exception is not integrated into a practical application because no additional structures are required. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements which are required by claim 1, nor does it meet any other considerations under MPEP 2106.05(a-h). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The only elements recited in claim 1 are a sequence encoding Glut1 (encompassing the naturally-occurring SLC2A1 gene) operatively linked to a promoter (encompassing the naturally-occurring Glut1 promoter, which is naturally operatively linked to the SLC2A1 gene, see GeneCards—SLC2A1), comprised in an expression cassette (which encompasses any sequence in a cell genome which can be transcribed and translated to express an encoded sequence).
Claim 1 recites an expression cassette, which constitutes a composition of matter—one of the statutory categories of invention.
Claim 1 recites a product which encompasses a product of nature as described in MPEP § 2106.04(b)(II). This product encompasses the naturally-occurring SLC2A1 gene in a cell genome, wherein the SLC2A1 gene is operatively linked to the associated Glut1 promoter. The specification teaches that the GLUT1 gene (SLC2A1) has an endogenous promoter—the Glut1 promoter (paragraph [0005], “the promoter of the endogenous GLUT1 gene”). The art teaches that the SLC2A1 gene is naturally occurring in humans, and has an endogenous promoter (see GeneCards—SLC2A1). Furthermore, an expression cassette encompasses any promoter-gene sequence in a genome, from which an RNA or protein can be expressed, including the promoter-gene sequence in the human genome encoding the GLUT1 protein.
According to Step 2A, Prong Two, set forth in MPEP § 2106.04(II)(A)(2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. These considerations are set forth in MPEP § 2106.05(a)-(h). This analysis turns to the additional steps or elements recited within the claims. Claim 1 does not recite any additional steps or elements beyond what has been determined to be a judicial exception.
There are no additional elements that reflect an implementation with a particular additional element nor is it transformed or reduced to a different state, nor which meets any other considerations under MPEP § 2106.05(a)-(h), such that the claimed product amount to significantly more than the judicial exceptions.
For all these reasons, claim 1 is directed to a judicial exception without significantly more and is rejected.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 15, 21, 23-24, 44-45 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Vivo (US20180042991A1).
Regarding claim 1, De Vivo teaches an expression cassette comprising a transgene encoding Glut1, wherein the transgene is operatively linked to a promoter (claim 1).
Regarding claim 3, De Vivo teaches that the promoter is a ubiquitous or constitutive promoter (chicken beta actin promoter, CMV promoter) (claim 3; paragraph [0049]).
Regarding claim 15, De Vivo teaches that the expression cassette comprises: a polyA signal (Table 1; paragraphs [0045], [0047]); and a polynucleotide of SEQ ID NO:32 (Table 1; SEQ ID NO:32 is 99.8% identical to instant SEQ ID NO:5, see alignment below).
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Regarding claim 21, De Vivo teaches that the expression cassette is flanked by 5’ and 3’ ITRs (see Table 1), wherein the 5’ and 3’ ITRs have the sequences of SEQ ID NO:29 and 34, respectively (SEQ ID NOs:29 and 34 are at least 75% identical to instant SEQ ID NOs:6 and 7, see alignments below).
SEQ ID NO:29 aligned to instant SEQ ID NO:6:
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SEQ ID NO:36 aligned to instant SEQ ID NO:7:
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Regarding claim 23, De Vivo teaches that the vector is used in a method of gene therapy, and thus is a gene therapy vector (claim 14).
Regarding claim 24, De Vivo teaches that the gene therapy vector is a recombinant AAV (rAAV) vector, wherein the rAAV is AAV8 or AAV9 (claims 1, 5).
Regarding claim 44, De Vivo teaches a composition comprising the vector and a pharmaceutical carrier (claims 9-10), and teaches pharmaceutical compositions comprising the vector (paragraphs [0057], [0075]).
Regarding claim 45, De Vivo teaches a kit comprising the vector (claims 11-12).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 15, 21-24, 44-45 is/are rejected under 35 U.S.C. 103 as being unpatentable over De Vivo (US20180042991A1) in view of GenBank: AB553834.1 (2010).
Regarding claim 1, De Vivo teaches an expression cassette comprising a transgene encoding Glut1, wherein the transgene is operatively linked to a promoter (claim 1).
Regarding claim 3, De Vivo teaches that the promoter is a ubiquitous or constitutive promoter (chicken beta actin promoter, CMV promoter) (claim 3; paragraph [0049]).
Regarding claim 15, De Vivo teaches that the expression cassette comprises: a polyA signal (Table 1; paragraphs [0045], [0047]); and a polynucleotide of SEQ ID NO:32 (Table 1; SEQ ID NO:32 is 99.8% identical to instant SEQ ID NO:5, see alignment below).
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Regarding claim 21, De Vivo teaches that the expression cassette is flanked by 5’ and 3’ ITRs (see Table 1), wherein the 5’ and 3’ ITRs have the sequences of SEQ ID NO:29 and 34, respectively (SEQ ID NOs:29 and 34 are at least 75% identical to instant SEQ ID NOs:6 and 7, see alignments below).
SEQ ID NO:29 (Db) aligned to instant SEQ ID NO:6 (Qy):
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SEQ ID NO:34 (Db) aligned to instant SEQ ID NO:7 (Qy):
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Regarding claim 22, De Vivo teaches an expression cassette (pAAV9-CB6 PI hGlut1, Table 1) comprising a promoter sequence of SEQ ID NOs:30 (CMV IE enhancer) and 31 (CB promoter), an hGlut1 cDNA sequence of SEQ ID NO:32, and a polyA signal of SEQ ID NO:33 (see Table 1). SEQ ID NO:10, recited by instant claim 22, is depicted in instant Fig. 3 (see instant specification [0055]). Instant Fig. 3 shows that instant SEQ ID NO:10 comprises three significant sequence elements: a CAG promoter (instant SEQ ID NO:44, described on page 31, see alignment below between SEQ ID NO:44 and SEQ ID NO:10), SLC2A1 (instant SEQ ID NO:5, see alignment below between SEQ ID NO:5 and SEQ ID NO:10), and a polyadenylation signal (instant SEQ ID NO:75, see alignment below between SEQ ID NO:75 and SEQ ID NO:10).
Instant SEQ ID NO:44 (Qy) and SEQ ID NO:10 (Db):
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Instant SEQ ID NO:5 (Qy) and SEQ ID NO:10 (Db):
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Instant SEQ ID NO:75 (Qy) and SEQ ID NO:10 (Db):
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A BLAST search of the components of instant SEQ ID NO:10 not accounted for by SEQ ID NOs:44, 5, and 75 did not produce any alignments, with the exception of expression or cloning vectors (see sample of results below).
Nucleotides 596-1662:
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Based on these search results and alignments, and in the absence of any teaching to the contrary in the disclosure, the promoter, SLC2A1, and polyA sequences of SEQ ID NO:10 are considered to be the only sequence elements holding patentable weight; the remainder of SEQ ID NO:10, in particular nucleotides 596-1662, is considered to comprise unspecified sequences which do not affect the structure or function of the defined promoter, SLC2A1, and polyA sequences, and do not affect the required functionality of the claimed expression cassette, and which are the incidental product of insertion of the promoter, coding, and polyA sequences into a generic, unspecified expression vector.
De Vivo teaches an expression cassette of SEQ ID NO:28 comprising, 5’ to 3’: a promoter sequence 97.6% identical to instant SEQ ID NO:44 (accounting for 559 nucleotides of instant SEQ ID NO:10); a coding sequence 99.8% identical to instant SEQ ID NO:5 (accounting for 1473 nucleotides of instant SEQ ID NO:10); and a polyA sequence 9.6% identical to instant SEQ ID NO:75 (accounting for 19 nucleotides of SEQ ID NO:10) (Table 1; see alignments below).
SEQ ID NO:28 and instant SEQ ID NO:44:
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SEQ ID NO:28 and instant SEQ ID NO:5:
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SEQ ID NO:28 and instant SEQ ID NO:75:
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De Vivo thus accounts for 2,051 of 2,251 nucleotides of the combination of instant SEQ ID NOs:44, 5, and 75 (91.1% identity), or 2,051 of 2,347 nucleotides of SEQ ID NO:10, excluding nucleotides 596-1662 (87.4% identity), rendering obvious expression cassettes at least 87% identical to instant SEQ ID NO:10, excluding nucleotides 596-1662, which, as shown above, correspond to generic, unspecified cloning vector sequences.
Furthermore, one cloning vector comprising a sequence 100% identical to nucleotides 596-1662 of SEQ ID NO:10 has the GenBank accession number AB553834.1 (deposited 2010; see alignment below). This cloning vector is described as a human artificial chromosome vector useful for gene therapy (see GenBank description, specifically “REFERENCE—TITLE” and the name of the vector). It would have been obvious to an artisan at the time of filing that the expression vector of claim 1, with an intended use in gene therapy in humans (instant specification paragraph [0009]), should be inserted into a vector for expression in humans, wherein the vector is useful for gene therapy applications; it thus would have been obvious to the artisan that the human artificial chromosome vector of GenBank AB553834.1 could be used for this purpose, rendering obvious nucleotides 596-1662 of instant SEQ ID NO:10.
GenBank: AB553834.1 aligned to instant SEQ ID NO:10 nts 596-1662:
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Regarding claim 23, De Vivo teaches that the vector is used in a method of gene therapy, and thus is a gene therapy vector (claim 14).
Regarding claim 24, De Vivo teaches that the gene therapy vector is a recombinant AAV (rAAV) vector, wherein the rAAV is AAV8 or AAV9 (claims 1, 5).
Regarding claim 44, De Vivo teaches a composition comprising the vector and a pharmaceutical carrier (claims 9-10), and teaches pharmaceutical compositions comprising the vector (paragraphs [0057], [0075]).
Regarding claim 45, De Vivo teaches a kit comprising the vector (claims 11-12).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over De Vivo (US20180042991A1), as applied to claim 1 above, and further in view of Nicklin (2001).
The teachings of De Vivo are discussed above and render obvious the required limitations of claim 1.
However, De Vivo does not teach that the promoter is an endothelial-specific promoter. De Vivo does teach that expression of the expression cassette in the blood-brain barrier endothelium is desired and preferred (claims 3, 17; paragraphs [0011]-[0012], [0021]).
Nicklin teaches endothelium-specific promoters.
Regarding claim 2, Nicklin teaches that FLT-1, ICAM-2, and VWF promoters are tissue-specific promoters, specific to endothelial cells (Abstract).
De Vivo teaches that “the predominant cellular site of action [of wild-type Glut1 protein] appears to be the endothelial cells of the brain micro-vessels where it functions in the facilitated transport of glucose across the blood-brain barrier” (paragraph [0021]), and teaches that the expression cassette must be able to be expressed in endothelial cells (claims 3, 17). While De Vivo teaches the use of constitutive promoters, such as CMV and CAG (claims 2, 4; paragraph [0049]), it would have been obvious to an artisan that endothelium-specific promoters known in the art could be used instead of constitutive promoters to drive expression of Glut1 specifically in endothelial cells—where De Vivo teaches Glut1 activity is most predominant, and where De Vivo teaches the expression cassette should be expressed. It would have been obvious to an artisan that such tissue-specific expression of the cassette of De Vivo would reduce expression of Glut1 in undesired tissues (see for example, paragraph [0140], wherein De Vivo teaches that expression of the cassette in liver could result in hypoglycemia, an undesired effect).
Conclusion
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636