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 claims 1, 2, and 36, as well as newly added dependent claims 87-105 and 115-126 (Group I) in the reply filed on 11/04/2025 is acknowledged. Claim 36 was subsequently cancelled in the amended claim set filed 12/24/2025.
Claims 67-86 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/04/2025. Claims 67-86 were cancelled in the reply filed 11/04/2025.
Accordingly, claims 1, 2, 87-105, and 115-126 are pending and under consideration.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/047,965 and 63/054,162, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Neither application 63/047,965 nor 63/054,162 disclose instant SEQ ID NO: 121. SEQ ID NO: 121 is explicitly recited and/or inherited by instant claims 2, 95-105, 118-121, and 124-126. Therefore, the effective filing date of instant claims 2, 95-105, 118-121, and 124-126 is the filing date of provisional Application No. 63/067,264, which was filed 08/18/2020.
Furthermore, none of Application Nos. 63/047,965, 63/054,162, 63/07264, nor 63/141,918 disclose the B-chain or C-chain modifications of instant claim 1 (inherited by instant claims 87-94, 115-117, and 122-123), nor do they disclose the furin cleavage site of instant claim 88. Accordingly, the effective filing date of instant claims 1, 87-94, 115-117, and 122-123 is the filing date of provisional Application No. 63/188,778, which was filed 05/14/2021.
Information Disclosure Statement
Receipt of information disclosure statements on 12/30/2022, 08/14/2023, 11/01/2024, 01/17/2025, and 11/07/2025 is acknowledged. The signed and initialed PTO-1449‘s have been mailed with this action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
►Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See Paragraph [0276].
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings filed 12/30/2022 are acceptable.
Specification
The specification filed 12/30/2022 (and amendments thereof filed 12/30/2022 and 08/14/2023) is acceptable.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 87, 94, 95, 104, 105, 119, 123, 125, and 126 are objected to because of the following informalities:
Claim 87 recites “the signal peptide an IL-6 signal sequence…”, which does not comport with standard grammatical and/or linguistic conventions, as it lacks a verb such as “is” preceding “an IL-6 signal sequence…”. It would be remedial to amend the instant claim to recite “the signal peptide is an IL-6 signal sequence…” (bolded emphasis added). This is merely an example set forth by the Examiner and is not intended to be limiting.
Both claims 96 and 119 recite “the human Ins protein comprises the amino acid sequence of amino acids 25-110 of SEQ ID NO: 41, amino acids 25-110 of SEQ ID NO: 144, amino acids 25-110 of SEQ ID NO: 145, SEQ ID NO: 41, SEQ ID NO: 144, or SEQ ID NO: 145,” which is not written in a clear fashion. It appears that the instant claim language recites that the claimed insulin protein comprises the amino acid sequence of amino acids 25-110 of SEQ ID NOs: 41, 144, or 145. It would be remedial to amend the instant claim language such that this is more clearly recited.
Claims 94, 104, 105, 123, 125, and 126 all recite capsid serotypes selected from “AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVRH8, AAVrh9, AAV9, AAVrh10, AAV10, AAVRH10, AAV11, or AAV12” (bolded emphasis added). However, the recitation of “AAVrh10” and “AAVRH10” is identical. Thus, capsid AAAVrh10/AAVRH10 is recited twice in each of the claims noted above. It would be remedial to recite AAVrh10/AAVRH10 once in each of the claims noted above.
Appropriate correction is required.
Claim Rejections - 35 USC § 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 2, 96-105, 115-126 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.
Claims 2, 96-105, and 115-126 are drawn (either themselves or by virtue of their dependency) to a set of nucleic acids encoding human insulin and/or glucokinase, wherein said nucleic acids comprise at least 85% identity to recited sequence identifiers. The rejected claims thus comprise a set of nucleic acids that encompass a large number of variable residues, all variations of which much encode functional human insulin and/or glucokinase.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes sequences and ORFs thereof comprising the instantly claimed sequences. No description is provided of variants thereof with at least 85% identity to the instantly claimed sequences.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the instantly claimed sequences. The results are not necessarily predictive of variants thereof comprising at least 85% identity to the same. Such variants encompass a wide breadth of nucleic acid sequences, as 85% identity encompasses a large number of variable residues, all of which must encode functional human insulin and/or glucokinase. Thus, it is impossible for one to extrapolate from the few examples described herein those sequences encoding human insulin and/or glucokinase that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of sequences comprising at least 85% identity to the instantly claimed sequences that also encode functional human insulin and/or glucokinase. As is known to those of ordinary skill in the art, amino acid sequences of protein products are determined by the corresponding nucleic acid sequence (reviewed in Crick, 1970). Therefore, any variation in the nucleic acid sequence must necessarily result in variation of the corresponding amino acid sequence translated from the same. This variation may be synonymous or non-synonymous, wherein non-synonymous substitutions are tolerated at a lower rate than synonymous substitutions. However, even synonymous substitutions have been found to impact the biological effect of the encoded protein (reviewed in Hunt et al., 2014: see especially Figure 1). Furthermore, the instant claim set does not limit the claimed sequence variation to synonymous substitutions and therefore necessarily encompasses both synonymous and non-synonymous substitutions, both of which would be expected to impact the biological effect of the encoded protein, as reviewed in Hunt et al., 2014.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 2, 96-105, 115-118, and 120-126.
Claim Rejections - 35 USC § 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 2, 96, 99-104, 118, 120, 124, and 125 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.
Instant claims 2, 96, 99-104, 118, 120, 124, and 125 all require “a polynucleotide comprising a nucleic acid encoding a human insulin (Ins) protein, wherein the nucleic acid comprises a sequence…[selected from multiple recited sequences]…or any combination thereof” (bolded emphasis added; recited at instant claim 2-inherited by instant claims 96, 99-104, 118, 120, 124, and 125). The recitation of “or any combination thereof” obscures the metes and bounds of protection sought. Per the Examples of the instant specification, each of the recited sequences encodes a functional human insulin protein. However, no guidance is offered regarding combinations of these sequences. The term “combination thereof” may be broadly interpreted to recite combinations wherein multiple sequences are joined together, wherein multiple parts of multiple sequences are joined together, as well as all variants thereof. It is not clear whether all of these combinations would encode a functional human insulin protein, nor is it clear what combinations are being claimed, especially in the absence of any clarifying explanation or definition in the instant specification.
It would be remedial to clearly define what combination(s) is/are being claimed such that the metes and bounds of protection sought are clear to those of ordinary skill in the art.
Claims 115-125 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.
Instant claims 115-125 all require “a polynucleotide comprising a nucleic acid encoding a human glucokinase (Gck) protein, wherein the nucleic acid encoding the human Gck protein comprises a sequence…[selected from multiple recited sequences]…or any combination thereof” (bolded emphasis added; recited at instant claims 115, 118, 122, and 124-inherited by instant claims 116, 117, 119, 120, 123, and 125). The recitation of “or any combination thereof” obscures the metes and bounds of protection sought. Per the Examples of the instant specification, each of the recited sequences encodes a functional human glucokinase protein. However, no guidance is offered regarding combinations of these sequences. The term “combination thereof” may be broadly interpreted to recite combinations wherein multiple sequences are joined together, wherein multiple parts of multiple sequences are joined together, and all variants thereof. It is not clear whether all of these combinations would encode a functional human glucokinase protein, nor is it clear what combinations are being claimed, especially in the absence of any clarifying explanation or definition in the instant specification.
It would be remedial to clearly define what combination(s) is/are being claimed such that the metes and bounds of protection sought are clear to those of ordinary skill in the art.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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.
Claims 1 and 89-91 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2005/0039235 A1 (hereinafter Moloney).
With regard to claim 1, which recites “a polynucleotide encoding a human insulin (Ins) protein comprising (i) a nucleotide sequence encoding a signal peptide, wherein the signal peptide is not a wild-type preproinsulin signal sequence, and (ii) a nucleotide sequence encoding a proinsulin polypeptide comprising an amino acid modification at a position selected from amino acid B10, B28, and/or B29 of the human insulin B-chain, C1 and/or C32 of the human insulin C-chain, or any combination thereof relative to the corresponding amino acid position in wild-type proinsulin,” Moloney discloses methods for the production of human insulin in plants (abstract; paragraph [0034]), said method comprising providing nucleic acid sequences encoding an insulin polypeptide (paragraph [0096]). These nucleic acid sequences are additionally disclosed to comprise a signal peptide such as a tobacco pathogenesis related protein signal sequence (paragraph [0120]), which is not a wild-type preproinsulin signal sequence, as instantly claimed. Furthermore, the recitation that the nucleotide sequence must encode a proinsulin polypeptide comprising an amino acid modification at a position selected from amino acid B10, B28, and/or B29 of the human insulin B-chain, C1 and/or C32 of the human insulin C-chain (or any combination thereof) may be interpreted under broadest reasonable interpretation to encompass proinsulin polypeptides comprising an amino acid modification at any one or more of amino acids B10, B28, B29, C1, or C32. Moloney discloses that insulin analogs of use therein include human insulin molecules in which amino acid residue 28 of the B-chain (B28) has been changed from its natural proline residue into aspartate, lysine, or isoleucine, as well as modification of the lysine residue at B29 to a proline residue (paragraph [0098]). Thus, Moloney discloses each and every limitation of instant claim 1.
With regard to claim 89, which recites “an expression cassette comprising the polynucleotide of claim 1 operably linked to a promoter,” as set forth above, Moloney discloses the polynucleotide of claim 1. Moloney further discloses a recombinant expression vector comprising the same (which is considered to read on the instantly claimed expression cassette, as said expression vector must comprise said expression cassette), wherein the polynucleotide disclosed therein comprises a promoter capable of controlling the expression thereof (paragraph [0130]). Thus, Moloney discloses each and every limitation of instant claim 89.
With regard to claim 90, which recites “a vector comprising the polynucleotide of claim 1,” as set forth above, Moloney discloses the polynucleotide of claim 1. Moloney further discloses a recombinant expression vector comprising the same (paragraph [0130]). Thus, Moloney discloses each and every limitation of instant claim 90.
With regard to claim 91, which recites “the vector [of claim 90] is a viral vector, a non-viral vector, a plasmid, a lipid, or a lysosome,” as set forth above, Moloney discloses the vector of instant claim 90. Moloney further discloses that suitable recombinant vectors include the Ti and Ri plasmids (paragraph [0136]), which read on the instantly claimed plasmid vectors of instant claim 91. Thus, Moloney discloses each and every limitation of instant claim 91.
Claims 2, 99-104, and 118 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022).
With regard to claim 2, which recites “a polynucleotide comprising a nucleic acid encoding a human insulin (Ins) protein, wherein the nucleic acid comprises a sequence at least 85%...identical to any one of…nucleic acids 88-345 or any of SEQ ID NOs: 117-122…or any combination thereof,” Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract), wherein insulin is encoded by SEQ ID NO: 1 (page 4, lines 6-10). As shown in the alignment of Appendix I, SEQ ID NO: 1 of Bosch comprises 97.5% sequence identity to nucleic acids 88-345 of instant SEQ ID NO: 121, as instantly claimed. Thus, Bosch discloses each and every limitation of instant claim 2.
With regard to claim 99, which recites “an expression cassette comprising the polynucleotide of claim 2 operably linked to a promoter,” as set forth above, Bosch discloses the polynucleotide of claim 2. Furthermore, Bosch discloses expression constructs (which are considered to read on the instantly claimed expression cassette) comprising the nucleotide sequences encoding an insulin as taught therein, wherein said nucleotide sequences are operably linked to a promoter to direct expression thereof (page 21, lines 17-21). Thus, Bosch discloses each and every limitation of instant claim 99.
With regard to claim 100, which recites “a vector comprising the polynucleotide of claim 2,” as set forth above, Bosch discloses the polynucleotide of claim 2. Furthermore, Bosch discloses viral vectors comprising the nucleotide sequences encoding an insulin as taught therein (page 12, lines 12-16). Thus, Bosch discloses each and every limitation of instant claim 100.
With regard to claim 101, which recites “the vector [of claim 100] is a viral vector, a non-viral vector, a plasmid, a lipid, or a lysosome,” as set forth above, Bosch discloses the vector of claim 100. Furthermore, as set forth above, Bosch discloses viral vectors comprising the nucleotide sequences encoding an insulin as taught therein (page 12, lines 12-16). Thus, Bosch discloses each and every limitation of instant claim 101.
With regard to claim 102, which recites “the vector [of claim 101] is an adeno-associated virus (AAV) vector or a Lentivirus vector,” as set forth above, Bosch discloses the viral vector of claim 101. Furthermore, Bosch discloses that the viral vectors taught therein may be an adeno-associated virus vector (page 12, lines 12-16). Thus, Bosch discloses each and every limitation of instant claim 102.
With regard to claim 103, which recites “a recombinant AAV (rAAV) particle, comprising an AAV capsid and a vector genome comprising the polynucleotide of claim 2,” as set forth above, Bosch discloses the polynucleotide of claim 2. Furthermore, Bosch discloses that the AAV vectors taught therein comprise a recombinant AAV vector, which comprises part of an AAV genome encapsidated in a protein shell of a capsid protein derived from an AAV serotype, such as AAV 1, 2, 3, 4, 5, and others (page 25, lines 24-33), as instantly claimed. These recombinant AAV vectors are disclosed to be cultured in host cells to extract particles thereof at page 28, lines 10-12. Therefore, given that the recombinant AAV vectors taught in Bosch comprise all the claimed components and are disclosed to have utility in production of particles thereof, it is considered that Bosch discloses each and every limitation of instant claim 103.
With regard to claim 104, which recites “the AAV capsid serotype [of the rAAV particle of claim 103] is selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVRH8, AAVrh9, AAV9, AAVrh10, AAV10, AAVRH10, AAV11, or AAV12,” as set forth above, Bosch discloses the rAAV particle of claim 103. Furthermore, Bosch discloses that the capsid protein thereof may be derived from an AAV serotype, such as AAV 1, 2, 3, 4, 5, and others (page 25, lines 24-33), as instantly claimed. Thus, Bosch discloses each and every limitation of instant claim 104.
With regard to claim 118, which recites “a composition comprising: (i) the polynucleotide encoding the human Ins protein of claim 2 and (ii) a polynucleotide comprising a nucleic acid encoding a human glucokinase (Gck) protein, wherein the nucleic acid encoding the human Gck protein comprises a sequence at least 85%...identical to any one of SEQ ID NOs: 61-80 and 162, or any combination thereof,” as set forth above, Bosch discloses the polynucleotide of claim 2. Bosch brodaly discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract). These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Bosch further discloses a nucleotide sequence encoding a glucokinase corresponding to SEQ ID NO: 2. As shown in the alignment of Appendix II, SEQ ID NO: 2 of Bosch comprises 90.5% sequence identity to instant SEQ ID NO: 68. Bosch further discloses a composition comprising said viral vectors/constructs (page 11, line 32-page 12, line 3). Thus, Bosch discloses each and every limitation of instant claim 118.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 87 is rejected under 35 U.S.C. 103 as being unpatentable over US 2005/0039235 A1 (hereinafter Moloney) as applied to claim 1 above, and further in view of McCown, 2006 (hereinafter McCown.
The disclosure of Moloney is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the signal sequences of instant claim 87.
With regard to claim 87, which recites “the signal peptide [of the polynucleotide of claim 1 is] an IL-6 signal sequence or a fibronectin signal sequence,” as set forth above, Moloney discloses the polynucleotide of claim 1. While Moloney teaches that the polynucleotides disclosed therein comprise signal peptides (paragraph [0120]), Moloney is silent as to the instantly claimed signal sequences. This deficiency is cured by McCown, which discloses that the fibronectin signal sequence facilitates constitutive secretion of gene therapy products in vivo, thereby providing effective gene therapy to patients in need thereof (abstract; page 63, column 2, paragraph 1). Thus, McCown discloses each and every additional limitation of instant claim 87.
Given that Moloney discloses the polynucleotide encoding insulin of claim 1 (and comprising a signal peptide), as set forth above, and that McCown discloses that the fibronectin signal sequence facilitates constitutive secretion of gene therapy products in vivo, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to utilize the fibronectin signal sequence disclosed in McCown as the signal peptide of the polynucleotide disclosed in McCown to predictably constitutively secrete the therapeutic product (i.e. insulin) encoded therein. One would have been motivated to make such a modification in order to receive the expected benefit of generating a polynucleotide construct capable of constitutively secreting the therapeutic product (i.e. insulin) encoded therein.
Claim 88 is rejected under 35 U.S.C. 103 as being unpatentable over US 2005/0039235 A1 (hereinafter Moloney) as applied to claim 1 above, and further in view of Han et al., 2011 (hereinafter Han).
The disclosure of Moloney is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the furin cleavage site of instant claim 88.
With regard to claim 88, which recites “the polynucleotide [of claim 1] further comprises a sequence coding for a furin cleavage site,” as set forth above, Moloney discloses the polynucleotide of claim 1. However, Moloney does not disclose that the polynucleotides disclosed therein comprise a furin cleavage site. This deficiency is cured by Han. Han discloses insulin gene therapy using a hepatocyte-specific and glucose-responsive synthetic promoter, wherein the supplied insulin is cleavable by furin (via furin cleavage sites at the B-chain and C-peptide junction), thereby controlling blood glucose levels and remitting hyperglycemia in diabetic mice (abstract; page 475, column 1, paragraph 2; section “Generation of recombinant adenovirus”). Thus, Han discloses each and every additional limitation of instant claim 88.
Given that Moloney discloses the polynucleotide encoding insulin of claim 1, as set forth above, and that Han discloses insulin gene therapy vectors comprising a furin cleavage site to control blood glucose levels and remit hyperglycemia, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the polynucleotide encoding insulin of Moloney to further comprise a furin cleavage site (as disclosed in Han) to predictably control blood glucose levels and remit hyperglycemia. One would have been motivated to make such a modification in order to receive the expected benefit of generating a polynucleotide construct capable of controlling blood glucose levels in patients in need thereof.
Claims 91-94, 115, 122, and 123 are rejected under 35 U.S.C. 103 as being unpatentable over US 2005/0039235 A1 (hereinafter Moloney) as applied to claims 1 and 90 above, and further in view of WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022) and WO 2012/007458 A1 (hereinafter Ayuso López; as cited in the IDS filed 12/30/2022).
The disclosure of Moloney is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the viral vectors, particles, and capsids thereof of instant claims 91-94, nor does it teach the human glucokinase sequence of instant claim 115.
With regard to claim 91, which recites “the vector [of claim 90] is a viral vector, a non-viral vector, a plasmid, a lipid, or a lysosome,” as set forth above, Moloney discloses that suitable recombinant vectors include the Ti and Ri plasmids (paragraph [0136]), which read on the instantly claimed plasmid vectors of instant claim 91. However, Moloney does not disclose the viral vectors of instant claim 91. This deficiency is cured by Bosch. As set forth above, Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract). These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Thus, Bosch discloses each and every additional limitation of instant claim 91.
With regard to claim 92, which recites “the viral vector [of the vector of claim 91] is an adeno-associated virus (AAV) vector,” as set forth above, Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract). These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Thus, Bosch discloses each and every additional limitation of instant claim 92.
With regard to claim 93, which recites “a recombinant AAV (rAAV) particle, comprising an AAV capsid and a vector genome comprising the polynucleotide of claim 1,” as set forth above, Moloney discloses the polynucleotide of claim 1, as well as a vector comprising the same (paragraph [0130]). However, Moloney does not disclose an rAAV particle comprising an AAV capsid and said vector genome. This deficiency is cured by Bosch. Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract), wherein said vector is a recombinant AAV (rAAV) vector comprising an AAV genome encapsidated in a protein shell of a capsid protein derived from an AAV serotype (page 25, lines 24-28), as instantly claimed. These recombinant AAV vectors are disclosed to be cultured in host cells to extract particles thereof at page 28, lines 10-12. Therefore, given that the recombinant AAV vectors taught in Bosch comprise all the claimed components and are disclosed to have utility in production of particles thereof, it is considered that Bosch discloses each and every additional limitation of instant claim 93.
With regard to claim 94, which recites “the AAV capsid serotype [of the rAAV particle of claim 93] is selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVRH8, AAVrh9, AAV9, AAVrh10, AAV10, AAVRH10, AAV11, or AAV12,” as set forth above, Moloney and Bosch collectively disclose the rAAV particle of claim 93. Furthermore, Bosch discloses that the capsid protein thereof may be derived from an AAV serotype, such as AAV 1, 2, 3, 4, 5, and others (page 25, lines 24-33), as instantly claimed. Thus, Bosch discloses each and every additional limitation of instant claim 94.
With regard to claim 115, which recites “a composition comprising: (i) the polynucleotide encoding the human Ins protein of claim 1 and (ii) a polynucleotide comprising a nucleic acid encoding a human glucokinase (Gck) protein, wherein the nucleic acid encoding the human Gck protein comprises a sequence at least 85%...identical to any one of: SEQ ID NO:s 61-80 and 162, or any combination thereof,” as set forth above, Moloney discloses the polynucleotide encoding human insulin of instant claim 1 (abstract; paragraphs [0034] and [0096]). However, Moloney does not disclose the instantly claimed human glucokinase sequence. This deficiency is cured by Bosch. As set forth above, Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract). These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Bosch further discloses a nucleotide sequence encoding a glucokinase corresponding to SEQ ID NO: 2. As shown in the alignment of Appendix II, SEQ ID NO: 2 of Bosch comprises 90.5% sequence identity to instant SEQ ID NO: 68. Finally, Bosch further discloses a composition comprising said viral vectors/constructs (page 11, line 32-page 12, line 3). Thus, Bosch discloses each and every additional limitation of instant claim 115.
With regard to claim 122, which recites “a composition comprising (i) the recombinant AAV (rAAV) particle of claim 93 and (ii) a second recombinant AAV (rAAV) particle comprising an AAV capsid and a vector genome comprising a polynucleotide comprising a nucleic acid encoding a human glucokinase (Gck) protein, wherein the nucleic acid encoding the human Gck protein comprises a sequence at least 85%...identical to any one of SEQ ID NOs: 61-80 and 162, or any combination thereof,” as set forth above, Moloney and Bosch collectively disclose the rAAV particle of claim 93. While Moloney does not disclose the instantly claimed human glucokinase sequence and provision of a second rAAV particle comprising the same, this deficiency is cured by Bosch. As set forth above, Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract), wherein said vector is a recombinant AAV (rAAV) vector comprising an AAV genome encapsidated in a protein shell of a capsid protein derived from an AAV serotype (page 25, lines 24-28), as instantly claimed. These recombinant AAV vectors are disclosed to be cultured in host cells to extract particles thereof at page 28, lines 10-12. These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Bosch further discloses a nucleotide sequence encoding a glucokinase corresponding to SEQ ID NO: 2. As shown in the alignment of Appendix II, SEQ ID NO: 2 of Bosch comprises 90.5% sequence identity to instant SEQ ID NO: 68. While Bosch teaches a single vector comprising both insulin and glucokinase, Bosch discloses that each sequence is under the control of a separate promoter (page 3, lines 12-13). Per MPEP § 2144.04(V)(C), it is obvious to make components separable, especially when doing so would not interfere with the function of the claimed product. In the instant case, Bosch already teaches that each sequence may be expressed by separate promoters. Therefore, it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant application to make the single vector of Bosch separable into two separate vectors (and particles thereof), as instantly claimed. This assertion is supported by the disclosure of Ayuso López, which discloses a first vector carrying the insulin gene and a second vector carrying the glucokinase gene (page 7, lines 24-27). Thus, Bosch and Ayuso López collectively disclose each and every additional limitation of instant claim 122.
With regard to claim 123, which recites “the AAV capsid serotype of the rAAV particle and/or the second rAAV particle [of the composition of claim 122] is selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVRH8, AAVrh9, AAV9, AAVrh10, AAV10, AAVRH10, AAV11, or AAV12,” as set forth above, Moloney and Bosch collectively disclose the rAAV particle of claim 93. Furthermore, Bosch discloses that the capsid protein thereof may be derived from an AAV serotype, such as AAV 1, 2, 3, 4, 5, and others (page 25, lines 24-33), as instantly claimed. Thus, Bosch discloses each and every additional limitation of instant claim 123.
Given that Moloney discloses the polynucleotide encoding insulin of claim 1 and vectors thereof, as set forth above, and that Bosch discloses single-AAV vector gene constructs (and rAAV particles thereof further comprising AAV 1, 2, 3, 4, or 5 serotypes) comprising insulin (encoded by SEQ ID NO: 1) and glucokinase genes (encoded by SEQ ID NO: 2), it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to package the polynucleotide encoding insulin of Moloney into a vector (as also disclosed in Moloney) such as AAV vectors (and rAAV particles thereof) expressing both insulin and glucokinase (separately) as disclosed in Bosch (see MPEP § 2144.04(V)(C) and Ayuso López) to predictably generate a therapeutic AAV vector construct to deliver insulin and glucokinase to patients in need thereof. One would have been motivated to make such a modification in order to receive the expected benefit of generating a therapeutic AAV vector construct to deliver insulin and glucokinase to patients in need thereof.
Claims 95, 96, 119, and 120 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022) as applied to claims 2 and 118 above, and further in view of US 2005/0039235 A1 (hereinafter Moloney).
The disclosure of Bosch is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the insulin amino acid sequence of instant claim 95, the signal peptide of claims 96 and 120, or the glucokinase sequence of claim 119.
With regard to claim 95, which recites “the human Ins protein [encoded by the polynucleotide of claim 2] comprises the amino acid sequence of any of amino acids 25-110 of SEQ ID NO: 41, amino acids 25-110 of SEQ ID NO: 144, amino acids 25-110 or SEQ ID NO: 145, SEQ ID NO: 41, SEQ ID NO: 144, or SEQ ID NO: 145,” as set forth above, Bosch discloses the polynucleotide of claim 2. However, Bosch is silent as to the amino acid sequence of the insulin claimed therein. This deficiency is cured by Moloney. As previously set forth, Moloney discloses polynucleotides encoding insulin (abstract; paragraphs [0034] and [0096]). Moloney further discloses the corresponding amino acid sequences of the insulin-encoding polynucleotides taught therein. For example, SEQ ID NO: 89 of Moloney is disclosed to correspond to a synthetic proinsulin (Table 1), which reads on the instantly claimed human insulin protein. Furthermore, as shown in the alignment of Appendix III, SEQ ID NO: 89 of Moloney comprises 100% sequence identity to amino acids 25-110 of instant SEQ ID NO: 41. Thus, Moloney discloses each and every additional limitation of instant claim 95.
With regard to claim 96, which recites “the human Ins protein [of the polynucleotide of claim 2] comprises a signal peptide,” as set forth above, Bosch discloses the polynucleotide of claim 2. However, Bosch is silent as to the instantly claimed signal peptide. This deficiency is cured by Moloney. As set forth above, Moloney discloses polynucleotides encoding insulin (abstract; paragraphs [0034] and [0096]), wherein said nucleic acid sequences are additionally disclosed to comprise a signal peptide such as a tobacco pathogenesis related protein signal sequence to target the nucleic acid to the endomembrane system such that the encoded insulin can be secreted (paragraph [0120]). Thus, Moloney discloses each and every additional limitation of instant claim 96.
With regard to claim 119, which recites “the human Ins protein [of the composition of claim 118] comprises the amino acid sequence of amino acids any of amino acids 25-110 of SEQ ID NO: 41, amino acids 25-110 of SEQ ID NO: 144, amino acids 25-110 or SEQ ID NO: 145, SEQ ID NO: 41, SEQ ID NO: 144, or SEQ ID NO: 145,” as set forth above, Bosch discloses the polynucleotide of claim 2 and the composition of claim 118. However, Bosch is silent as to the amino acid sequence of the insulin claimed therein. This deficiency is cured by Moloney. As previously set forth, Moloney discloses polynucleotides encoding insulin (abstract; paragraphs [0034] and [0096]). Moloney further discloses the corresponding amino acid sequences of the insulin-encoding polynucleotides taught therein. For example, SEQ ID NO: 89 of Moloney is disclosed to correspond to a synthetic proinsulin (Table 1), which reads on the instantly claimed human insulin protein. Furthermore, as shown in the alignment of Appendix III, SEQ ID NO: 89 of Moloney comprises 100% sequence identity to amino acids 25-110 of instant SEQ ID NO: 41. Thus, Moloney discloses each and every additional limitation of instant claim 119.
With regard to claim 120, which recites “the human Ins protein [of the composition of claim 118] comprises a signal peptide,” as set forth above, Bosch discloses the polynucleotide of claim 2. However, Bosch is silent as to the instantly claimed signal peptide. This deficiency is cured by Moloney. As set forth above, Moloney discloses polynucleotides encoding insulin (abstract; paragraphs [0034] and [0096]), wherein said nucleic acid sequences are additionally disclosed to comprise a signal peptide such as a tobacco pathogenesis related protein signal sequence to target the nucleic acid to the endomembrane system such that the encoded insulin can be secreted (paragraph [0120]). Thus, Moloney discloses each and every additional limitation of instant claim 120.
Given that Bosch discloses the polynucleotide encoding a human insulin of claim 2, and that Moloney discloses a human insulin sequence comprising signal sequence to promote secretion of the same, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to utilize the systems disclosed in Bosch to express a human insulin as disclosed in Moloney to predictably express a human insulin capable of being secreted. One would have been motivated to make such a modification in order to receive the expected benefit of generating a system capable of expressing a human insulin that is itself capable of being secreted.
Claim 116 is rejected under 35 U.S.C. 103 as being unpatentable over US 2005/0039235 A1 (hereinafter Moloney) in view of WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022) as applied to claims 1 and 115 above, and further in view of McCown, 2006 (hereinafter McCown).
The combined disclosures of Moloney and Bosch are described above and applied as before. However, these disclosures do not teach the signal sequences of instant claim 116.
With regard to claim 116, which recites “the polynucleotide encoding the human Ins protein [of the composition of claim 115] comprises an IL-6 signal sequence or a fibronectin signal sequence,” as set forth above, Moloney and Bosch collectively disclose the composition of claim 115. However, neither Moloney nor Bosch discloses the instantly claimed IL-6 or fibronectin signal sequences. This deficiency is cured by McCown, which discloses that the fibronectin signal sequence facilitates constitutive secretion of gene therapy products in vivo, thereby providing effective gene therapy to patients in need thereof (abstract; page 63, column 2, paragraph 1). Thus, McCown discloses each and every additional limitation of instant claim 116.
Given that Moloney and Bosch collectively disclose the composition of claim 115, as set forth above, and that McCown discloses that the fibronectin signal sequence facilitates constitutive secretion of gene therapy products in vivo, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to utilize the fibronectin signal sequence disclosed in McCown as the signal peptide of the polynucleotide disclosed in McCown to predictably constitutively secrete the therapeutic product (i.e. insulin) encoded therein. One would have been motivated to make such a modification in order to receive the expected benefit of generating a polynucleotide construct capable of constitutively secreting the therapeutic product (i.e. insulin) encoded therein.
Claim 117 is rejected under 35 U.S.C. 103 as being unpatentable over US 2005/0039235 A1 (hereinafter Moloney) in view of WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022) as applied to claims 1 and 115 above, and further in view of Han et al., 2011 (hereinafter Han).
The combined disclosures of Moloney and Bosch are described above and applied as before. However, these disclosures do not teach the furin cleavage site of instant claim 117.
With regard to claim 117, which recites “the polynucleotide encoding the human Ins protein [of the composition of claim 115] comprises a sequence coding for a furin cleavage site,” as set forth above, Moloney and Bosch collectively disclose the composition of claim 115. However, neither Moloney nor Bosch discloses the instantly claimed furin cleavage site. This deficiency is cured by Han. Han discloses insulin gene therapy using a hepatocyte-specific and glucose-responsive synthetic promoter, wherein the supplied insulin is cleavable by furin (via furin cleavage sites at the B-chain and C-peptide junction), thereby controlling blood glucose levels and remitting hyperglycemia in diabetic mice (abstract; page 475, column 1, paragraph 2; section “Generation of recombinant adenovirus”). Thus, Han discloses each and every additional limitation of instant claim 88.
Given that Moloney and Bosch collectively disclose the composition of claim 115, as set forth above, and that Han discloses insulin gene therapy vectors comprising a furin cleavage site to control blood glucose levels and remit hyperglycemia, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the polynucleotide encoding insulin of Moloney of the composition collectively disclosed by Moloney and Bosch to further comprise a furin cleavage site (as disclosed in Han) to predictably control blood glucose levels and remit hyperglycemia. One would have been motivated to make such a modification in order to receive the expected benefit of generating a polynucleotide construct capable of controlling blood glucose levels in patients in need thereof.
Claims 124 and 125 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/110518 A1 (hereinafter Bosch; as cited in the IDS filed 12/30/2022) as applied to claims 2 and 103 above, and further in view of WO 2012/007458 A1 (hereinafter Ayuso López; as cited in the IDS filed 12/30/2022).
The disclosure of Bosch is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the second rAAV particle of instant claim 124.
With regard to claim 124, which recites “a composition comprising (i) the recombinant AAV (rAAV) particle of claim 103 and (ii) a second recombinant AAV (rAAV) particle comprising an AAV capsid and a vector genome comprising a polynucleotide comprising a nucleic acid encoding a human glucokinase (Gck) protein, wherein the nucleic acid encoding the human Gck protein comprises a sequence at least 85%...identical to any one of SEQ ID NOs: 61-80 and 162, or any combination thereof,” as set forth above, Bosch discloses the rAAV particle of claim 103. Furthermore, as set forth above, Bosch discloses single-vector gene constructs comprising insulin and glucokinase genes (abstract), wherein said vector is a recombinant AAV (rAAV) vector comprising an AAV genome encapsidated in a protein shell of a capsid protein derived from an AAV serotype (page 25, lines 24-28), as instantly claimed. These recombinant AAV vectors are disclosed to be cultured in host cells to extract particles thereof at page 28, lines 10-12. These vectors include adeno-associated viral (AAV) vectors mediating insulin/glucokinase muscle gene transfer to counteract diabetic hyperglycemia (page 2, lines 23-27). Bosch further discloses a nucleotide sequence encoding a glucokinase corresponding to SEQ ID NO: 2. As shown in the alignment of Appendix II, SEQ ID NO: 2 of Bosch comprises 90.5% sequence identity to instant SEQ ID NO: 68. While Bosch teaches a single vector comprising both insulin and glucokinase, Bosch discloses that each sequence is under the control of a separate promoter (page 3, lines 12-13). Per MPEP § 2144.04(V)(C), it is obvious to make components separable, especially when doing so would not interfere with the function of the claimed product. In the instant case, Bosch already teaches that each sequence may be expressed by separate promoters. Therefore, it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant application to make the single vector of Bosch separable into two separate vectors (and particles thereof), as instantly claimed. This assertion is supported by the disclosure of Ayuso López, which discloses a first vector carrying the insulin gene and a second vector carrying the glucokinase gene (page 7, lines 24-27). Thus, Bosch and Ayuso López collectively disclose each and every additional limitation of instant claim 124.
With regard to claim 125, which recites “the AAV capsid serotype of the rAAV particle and/or the second rAAV particle [of the composition of claim 124] is selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVRH8, AAVrh9, AAV9, AAVrh10, AAV10, AAVRH10, AAV11, or AAV12,” as set forth above, Bosch discloses that the capsid protein of the rAAV particles thereof may be derived from an AAV serotype, such as AAV 1, 2, 3, 4, 5, and others (page 25, lines 24-33), as instantly claimed. Thus, Bosch discloses each and every additional limitation of instant claim 125.
Given that Bosch discloses each and every limitation of instant claims 124 and 125, with the exception of the separate rAAV particle of instant claim 124, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors of Bosch to separate insulin and glucokinase expression(see MPEP § 2144.04(V)(C) and Ayuso López) to predictably generate a therapeutic AAV vector construct composition to deliver insulin and glucokinase to patients in need thereof. One would have been motivated to make such a modification in order to receive the expected benefit of generating a therapeutic AAV vector construct composition to deliver insulin and glucokinase to patients in need thereof.
Double Patenting
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 2 and 99-104 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 5 of U.S. Patent No. 11,033,638 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent ‘638 is drawn to a viral expression construct comprising a nucleotide sequence at least 80% identical to the sequence set forth as SEQ ID NO: 1 (encoding an insulin), operably linked to a CMV promoter, as well as a viral vector, wherein said viral vector comprises said viral expression construct and is a recombinant adeno-associated virus vector, such as an AAV1 vector, as recited at patented claims 1, 2, and 5.
In comparison, instant claim 2 is drawn to a polynucleotide comprising a nucleic acid encoding a human insulin protein, wherein the nucleic acid comprises a sequence at least 85% identical to nucleic acids 88-345 of SEQ ID NO: 121. As shown in the alignment of Appendix IV, SEQ ID NO: 1 of patent ‘638 is 97.5% identical to nucleic acids 88-345 of SEQ ID NO: 121, thereby satisfying the claim limitations thereof. Furthermore, instant claim 99 recites “an expression cassette comprising the polynucleotide of claim 2 operably linked to a promoter,” such as the CMV promoter of patent ‘638. Instant claims 100-104 are drawn to an AAV viral vector and particle thereof, wherein said rAAV particle comprises the AAV capsid serotype AAV1. These recitations are not patentably distinct from that recited at patented claims 1, 2, and 5.
Claims 2, and 99-104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7-10, 16, and 19-22 of copending Application No. 17/614,390 (corresponds to US 2022/0226501 A1; claims amended 03/26/2026). Although the claims at issue are not identical, they are not patentably distinct from each other.
MPEP 804 II B 1 states:
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999)… Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).
The following rejections are in view of the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Copending application ‘390 is drawn to a method for treating and/or preventing neuroinflammation, neurodegeneration, and/or cognitive decline, said method comprising administering a gene construct comprising a nucleotide sequence encoding an insulin protein to a subject in need thereof, wherein the encoded insulin protein comprises a furin cleavage site and has a nucleotide sequence with at least 80% sequence identity to the nucleotide sequence of SEQ ID NOs: 45 or 46 (recited at copending claim 1) and wherein the corresponding amino acid sequence has at least 80% sequence identity to the amino acid sequence of SEQ ID NOs: 41 or 42. Copending claim 2 further recites that the nucleotide sequence encoding insulin is operably linked to a ubiquitous promoter. Copending claims 7-9 and 19-22 further recite that the gene construct is comprised in an AAV expression vector of serotype 1, 2, 3, 4, 5, 6, 7, 8, 9, rh10, or rh8, among others. Copending claim 10 is drawn to a pharmaceutical composition comprising said gene construct, while copending claim 16 is drawn to a pharmaceutical composition comprising the vector set forth above.
In comparison, instant claim 2 is drawn to a polynucleotide comprising a nucleic acid encoding a human insulin protein, wherein the nucleic acid comprises a sequence at least 85% identical to nucleic acids 88-345 of SEQ ID NO: 121. SEQ ID NO: 121 of the instant application is 97.5% identical to SEQ ID NO: 46 of the copending application over positions 88-345, as shown in Appendix V. Instant claims 99-104 further recite an expression cassette and a vector comprising the polynucleotide set forth above, wherein the vector is an AAV vector (and a particle comprising the same, wherein the particle comprises an AAV capsid and a vector genome) comprising a capsid serotype selected from AAV1, AAV2, AAV3, AAV4, AAV5, and others.
Thus, the recitation of copending application ‘390 is not patentably distinct from that of the instant application, as set forth above.
This is a provisional nonstatutory double patenting rejection.
Claims 2, 95-105, 118-121, and 124-126 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7-10, 27, 29-32, and 40 of copending Application No. 18/861,111 (corresponds to US 2025/0288693 A1; claims amended 10/10/2025). Although the claims at issue are not identical, they are not patentably distinct from each other.
MPEP 804 II B 1 states:
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999)… Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).
The following rejections are in view of the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Copending application ‘111 is drawn to a combination therapy, said therapy comprising a first and second AAV vector genome, respectively comprising an insulin expression cassette and a glucokinase expression cassette operably linked to separate promoters, wherein said expression cassettes are flanked by inverted terminal repeats, as recited at copending claim 1. Methods of using the same are recited at copending claims 2, 31, and 32. A composition comprising the same is recited at copending claim 40. rAAV particles comprising the same (as well as compositions thereof) are recited at copending claims 27, 29, and 30, wherein said particles comprise an AAV serotype selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh9, AAV9, AANrh10, AAV10, AAV11, and AAV12 (see copending claim 29).
Copending claim 7 limits the open reading frame of said insulin protein to a nucleotide sequence at least 85% identical to nucleic acids 88-345 of SEQ ID NO: 121 and of said glucokinase protein to a nucleotide sequence at least 85% identical to SEQ ID NO: 68. As shown in the alignments of Appendices VI and VII, copending and instant SEQ ID NOs: 68 and 121 are identical (see instant claims 2, 97, 98, 105, 121, and 126). Copending claim 8 further recites that the claimed insulin protein comprises the amino acid sequence of any of amino acids 25-110 of SEQ ID NOs: 41, 144, or 145, which is also recited at instant claims 95 and 119. The insulin of the copending application is further recited to comprise a signal peptide at copending claim 9, as at instant claims 96 and 120. This signal peptide is recited to be a fibronectin or IL-6 signal sequence at copending claim 10.
In comparison, instant claim 2 is drawn to a polynucleotide comprising a nucleic acid encoding a human insulin protein, wherein the nucleic acid comprises a sequence at least 85% identical to nucleic acids 88-345 of SEQ ID NO: 121. Instant claims 124-126 are further drawn to a composition comprising two recombinant AAV particles, wherein one rAAV particle encodes insulin and the other encodes glucokinase (comprising a sequence at least 85% identical to instant SEQ ID NO: 68, as set forth above). Compositions comprising the same are recited at instant claim 118, which comprises said insulin polynucleotide and a polynucleotide encoding a human glucokinase protein, as set forth above.
Instant claim 99 recites “an expression cassette comprising the polynucleotide of claim 2 [as set forth above] operably linked to a promoter,” while instant claim 100 recites “a vector comprising the polynucleotide of claim 2,” as set forth above. Said vector is recited to be an AAV vector at instant claims 101 and 102. Instant claim 103 recites “a recombinant AAV (rAAV) particle comprising an AAV capsid and a vector genome comprising the polynucleotide of claim 2,” as set forth above. Instant claims 104 and 105 recite that the AAV capsid of said rAAV particle is selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh9, AAV9, AANrh10, AAV10, AAV11, and AAV12 and that the polynucleotide encoding insulin comprises a sequence at least 85% identical to the sequence of SEQ ID NO: 121. As set forth above and shown in Alignment VI, instant and copending SEQ ID NO: 121 are identical.
Thus, the recitation of copending application ‘111 is not patentably distinct from that of the instant application, as set forth above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Claims 87, 94-95, 10-105, 119, 123, and 125-126 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
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/SARAH E ALLEN/ Examiner, Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
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