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 group I with elected SEQ ID NO: 2 in the reply filed on 3/30/2025 is acknowledged.
Claims 1-7, 8, 10, 13-15 and 18 are considered.
Claims 16-17, 19-21, 24-25, 27 and 29 are canceled.
Claims 9, 11-12, 22-23, 26 and 28 are withdrawn from consideration.
Sequence requirements
This application contains sequence disclosures on page 6, lines 24-26 that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/or Amino Acid Sequence Disclosures.
Full compliance with the sequence rules is required in response to this Office Action. A complete response to this office action should include both compliance with the sequence rules and a response to the Office Action set forth below. Failure to fully comply with both these requirements in the time period set forth in this office action will be held non-responsive.
MPEP 2421.02 cites: Summary of the Requirements of the Sequence Rules
Basically, the sequence rules define a set of symbols and procedures that are both
mandatory and the only way that an applicant is permitted to describe information about
a sequence that falls within the definitions used in the rules. Thus, 37 CFR 1.821 defines a
“sequence” and a “Sequence Listing” for the purpose of the rules, the requirements for
specific symbols, and formats for the “Sequence Listing,” the requirement for a computer
readable form (CRF) of the “Sequence Listing,” and the deadlines for complying with the
requirements. 37 CFR 1.822 to 37 CFR 1.824 set forth detailed descriptions of the
requirements that are mandatory for the presentation of sequence data, and 37 CFR
1.825 sets forth procedures that are available to an applicant in the event that amendments to the sequence information or replacement of the computer readable copy become necessary.
The sequence rules embrace all unbranched nucleotide sequences with ten or more bases
and all unbranched, non-D amino acid sequences with four or more amino acids, provided
that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply
to all sequences in a given application, whether claimed or not. All such sequences are
relevant for the purposes of building a comprehensive database and properly assessing
prior art. It is therefore essential that all sequences, whether only disclosed or also
claimed, be included in the database.
Claim Rejections - 35 USC § 112
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 7 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In particular, applicants do not have possession for a generic canine isoline polypeptide of SEQ ID NO: 2 that is 110 amino acid residues that further comprises 1 or 2 or 3of SEQ ID NO: 2.
MPEP § 2163.02 states, "[a] n objective standard for determining compliance with the written description requirement is “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’ ". The courts have decided: The purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.
In the instant case, according to the claimed genus of polypeptide and a functional of SEQ ID NO: 2 , which is based on110 amino acid residues in length, wherein 1, or 2 or 3 amino acid residues in any positions of the 110 amino acid positions can be substituted with 18 other amino acid residues. Accordingly, there are possibly astronomic numbers of 1.226 billion variants as applicants claimed (Total =(110 for 1)X18 in 1 power of variant + (100 for 2) X18 variants 2 powers + (110 for 3)X18 variants 3 power). However, the specification does not provide sufficient numbers of the variants of SEQ ID NO: 2 but one polypeptide with SEQ ID NO: 2.
The invention is, for purposes of the "written description" inquiry, whatever is now claimed. See Vas-Cathy, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description” Requirement (66 FR 1099-1111, January 5, 2001) states, "possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by 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" (Id. at 1104).
Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of nucleic acid molecules, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of nucleic acid sequences. Moreover, since the specification has not identified which nucleic acid molecules of the genus of sequences, one skilled in the art would not recognize that Applicant had possession of the claimed invention at the time the application was filed. There is insufficient support the generic claims as provided by the Interim Written Description Guidelines published in the June 15, 1998 Federal Register at Volume 63, Number 114, pages 32639-32645.
The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
Claims 1, 8 and 18 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Nissen et al. (DOMESTIC ANIMAL ENCOCHRINOLOGY 2012, Vol. 43, Issue 1, pages 16-25).
The rejected claim 1 is directed to a viral vector comprising a nucleic acid comprising a polynucleotide sequence encoding a canine insulin polypeptide, wherein the canine insulin is a variant having a mutation at one or more cleavage site (Claim 8). Claim 18 is also directed to a pharmaceutical composition suitable for treating a metabolic disease in a canine comprising an aqueous liquid and the viral vector.
Nissen et al. teach that a novel mutant furin-cleavable canine preproinsulin insert (cppI4) that was created through For the design of cppI4 four existing amino acids in the wild-type canine C-peptide part of the preproinsulin gene were substituted to create furin-cleavage sites, similar to the substitutions in hppI4 (Fig. 1) ,
The corresponding nucleotide sequence was optimized (reducing GC and CpG content, removing interfering restriction sites) and up- and down-stream BamHI restriction digestion enzyme sites were introduced, resulting in the following gene insert nucleotide sequence (added BamHI restriction enzyme sites underlined).
Subsequently, cppI1 was subcloned into nonviral plasmid pVAX (Invitrogen) and cppI4 into nonviral plasmids pVR1012-null (Vical Inc, San Diego, CA) and pVAX.
The expression plasmid VR1012, 4.9 kb and pVAX, 4.4 kb are both derived from pVAX.1 vector that is designed for use in the development of
Because a recombinant plasmid is considered as a recombinant virus for the bacteria cell, VR1012 and pVAX1 (or pVAX) are commonly used plasmid DNA vaccine vectors in research and clinical development. VR1012 is frequently used for high-level expression with a CMV promoter, while pVAX1 is an Invitrogen-designed plasmid optimized for safety and efficacy in DNA vaccine development
The cited reference anticipates claims 1, 8 and 18.
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.
Claims 1-6, 8, 13-15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Nissen et al. (DOMESTIC ANIMAL ENCOCHRINOLOGY 2012, Vol. 43, Issue 1, pages 16-25) and further in view of Calleja’s et al. (Diabetes, 2013, Vol. 62, pp. 1718-1729), Buning et al. (JOURNAL OF GENE MEDICINE, 2008, Vol. 10, pp. 717-733) and further in view of Moloney et al. (US 7547821.).
The rejected claims 1-4 are drawn to a viral vector comprising a nucleic acid comprising a polynucleotide sequence encoding a canine insulin polypeptide. Frost et al. teach inventions related to a super-fast acting insulin compositions comprising the isoline and a functional analog, wherein the vector comprises LTR as expression promoter and a signal peptide for initiating the recombinant proinsulin set forth as SEQ ID NO: 2 with a more 3 mutations to the originally polypeptide of SEQ ID NO: 2.
Nissen et al. teach that a novel mutant furin-cleavable canine preproinsulin insert (cppI4) that was created through For the design of cppI4 four existing amino acids in the wild-type canine C-peptide part of the preproinsulin gene were substituted to create furin-cleavage sites, similar to the substitutions in hppI4 (Fig. 1) ,
The corresponding nucleotide sequence was optimized (reducing GC and CpG content, removing interfering restriction sites) and up- and down-stream BamHI restriction digestion enzyme sites were introduced, resulting in the following gene insert nucleotide sequence (added BamHI restriction enzyme sites underlined).
However, Nissen et al. do not teach using an adeno-associated virus to deliver a canine insulin
Callejas et al. teach using adeno-associated viral vectors of serotype 1 (AAV1) to express insulin (Ins), wherein the insulin is modified with CG optimization. But Callejias et al. do not teach to express the canine insulin by AAV. (Please see the abstract and Method)., Callejas et al. do not teach any detail for making AAV vectors.
Buning et al. describe AAV molecular structures and method related how to construction of AAV expression vector in detail. about how to making a AAV vector and indicate that the transgene expression cassettes flanked by AAV-2 ITRs can be packaged into virions assembled from structural (capsid) proteins from different serotypes. This can be done by using helper plasmids encoding the AAV-2 rep ORF and a cap ORF of a different serotype. (See section of AAV based vectors. Buning et al. do not teach using canine insulin used in the construct.
Moloney et al. teach a Preproinsulin {Gene V00179} of canine insulin set forth in SEQ ID NO: 18 that is expressed as a recombinant insulin.
Therefore, it would have been obvious for a person with an ordinary skill in the art to be motivated using the same method taught by et al. using the recombinant adeno-associated viral vector (AAV) to express the proinsulin polypeptide of canine disclosed by Moloney et al. to arrive the recombinant viral vector capable of expressing the recombinant proinsulin of canine with a reasonable expectation of success.
Conclusion
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/ Primary Examiner, Art Unit 1671
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