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 .
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 - This application contains sequence disclosures in accordance with 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 - 1.825.
The sequence disclosures are located Claim 17 and pages 10 of the instant specification.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
A new title is required that is clearly indicative of the invention to which the claims are directed. MPEP 606 recites, “The title should be brief but technically accurate and descriptive and should contain fewer than 500 characters.” The current title exceeds the character limit and is verbose.
The following title is suggested: “Gene therapy vector for the expression of KRT5, KRT14, LAMB3, and COL7A1 utilizing the Vtvaf17 DNA vector”.
Claim Objections
Claim 17 and 18 are objected to because of the following informalities:
Regarding Claim 17, line 2 recites “orLAMB3” instead of “or LAMB3”.
Regarding Claims 17 and 18, MPEP 608.01(m) recites, “ Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation”.
Claim 17 recites a method with many steps within the same line. Each step should be separated by a line indention.
Claim 18 recites a plurality of methods within the same sentence. Claim 18 also uses repeated language “gene therapy DNA vector Vtvaf17”, but the preamble to Claim 18 already identifies the vector to be used. The applicant may amend the claim to identify the vectors once for concise language and list each method claimed separated by a line indention. Additionally, the vectors are claimed as SEQ ID NO. 1-4 in Claim 15, and the sequences may be used to identify the vectors.
Appropriate correction is required.
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.
Claim 17 and 18 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.
Regarding Claim 17, it is unclear what the order of steps in the method are. The use of “while” to separate steps is unclear as “while” means the steps are performed simultaneously, but these steps cannot be performed at the same time. The first step listed is cloning the coding region of the genes of interest into the DNA vector to obtain SEQ ID NO. 1-4. The next step begins with “while” and involves isolating total RNA from a biological tissue sample, performing RT-PCR to obtain cDNA of the gene of interest and cleaving the amplification product with restriction endonucleases. The next step also begins with “while” and involves cloning is performed with the DNA vector with restriction sites and does not describe what is being cloned into the vector. The next step involves “the selection” but no previous selection has been mentioned and it is unclear what step selection refers to. The next step says “at the same time, the following oligonucleotides are produced” but does not distinguish which previous step is performed simultaneously. These oligonucleotides were needed for the previous step of RT-PCR.
Further steps also says “at the same time” and produces oligonucleotides necessary to produce different DNA vectors. However, the initial claim language recites, “A method of gene therapy DNA vector production … carrying KRT5, or KRT14, or LAMB3, or COL7A1”. The claim as written performs many steps in parallel that one skilled in the art would perform sequentially and produces all the vectors for genes of interest simultaneously rather than just one vector as the “or” statement would require.
To overcome this rejection, the applicant may amend the claim to list the appropriate steps in sequential order with appropriate antecedents in clear and concise language.
Regarding Claim 18, the phrase "including" on line 5 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding Claim 16, Claim 15 recites a gene therapy DNA vector selected from SEQ ID NO. 1-4. Claim 16 limits the vectors of Claim 15 as comprising nucleotide sequences that are not antibiotic resistance genes, virus genes, or regulatory elements of viral genomes as structural elements. However, the additional limitations of Claim 16 are inherent to Claim 15 and do not further limit the scope of Claim 15 because the instant specification describes the vectors SEQ ID NO. 1-4 as not having antibiotic resistance genes, virus genes, or regulatory elements of viral genomes as structural elements (p. 9, lines 18-22). Therefore, Claim 16 is rejected under 35 USC 112(d) for failing to further limit the subject matter of Claim 15.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 15 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1 and 2 of U.S. Patent No. 11149279 B2 (identified as Savelieva) in view of Mãnnik, A. and Ustav M., WO 2018/185110, published October 11, 2018; Vincze, T., et. al., Nucleic Acids Research, Vol. 31, No. 13, p. 3688-3691, published July 1, 2003; and GenBank, KRT5, accession NM_000424.3, dated October 20, 2018; GenBank, KRT14, accession NM_000526.4, dated November 12, 2018; GenBank, LAMB3, accession NM_000228.2, dated September 16, 2018; GenBank, COL7A1 accession NM_000094.2, dated September 3, 2007
.
Savelieva recites in Claim 1, “a gene therapy DNA vector, VTvaf17, comprising the nucleic acid sequence depicted in SEQ ID NO. 1”.
Claim 1 of Savelieva does not teach the DNA vector has a coding region for KRT5, KRT14, LAMB3, or COL7A1 or SEQ ID NO: 1-4.
Mãnnik teaches an expression vector for gene therapy (p. 1, para 1) which contain a DNA coding region (p. 45, para 4) including KRT5, KRT14, LAMB3 and COL7A1 (p. 45-47). KRT5, KRT14, LAMB3 and COL7A1 are target genes for Epidermolysis Bullosa Simplex (p. 46, line 19, p. 47, lines 25-27).
Vincze teaches a method for identifying restriction sites within a sequence to determine where restriction enzyme cleave a sequence by using NEBcutter (p. 3688, Abstract). Using NEBcutter with the vector of Savelieva reveals a MCS site with commonly used enzymes EcoRI, BamHI, HindIII, and SalI from positions 1208-1238.
GenBank teaches the sequence of mRNA encoding KRT5 as accession NM_000424.3 with a coding sequence from positions 164 to 1936, of which the coding sequence has 100% alignment with SEQ ID NO: 1. GenBank teaches the sequence of mRNA encoding KRT14 as accession NM_000526.4 with a coding sequence from positions 62 to 1480, of which the coding sequence has 100% alignment with SEQ ID NO: 2. GenBank teaches the sequence of mRNA encoding LAMB3 as accession NM_000228.2 with a coding sequence from positions 145 to 3663, of which the coding sequence has 100% alignment with SEQ ID NO: 3. GenBank teaches the sequence of mRNA encoding COL7A1 as accession NM_000094.2 with a coding sequence between positions 99 and 8933, of which the coding sequence has 100% alignment with SEQ ID NO: 4.
Regarding Claim 15, it would be obvious to one skilled in the art to combine the vector of Savelieva for gene therapy with the target genes identified by Mãnnik to construct a gene therapy DNA vector based on VTvaf17 for treatment of epidermolysis bullosa wherein the vector has the coding region for KRT5, KRT14, LAMB3 or COL7A1 using the sequences provided by GenBank to create SEQ ID NO: 1-4 and restriction enzyme sites identified through the use of NEBcutter taught by Vincze. The results would be predictable to one skilled in the art because GenBank provides sequence information, NEBcutter provides guidance on where to insert sequences, and cloning genes into vectors are routine in the art. Therefore, the instant Claim 15 is obvious over Claim 1 of Savelieva, Mãnnik, Vincze, and GenBank.
Regarding Claim 18, Claim 15 is obvious over Savelieva, Mãnnik, Vincze, and GenBank.
Claim 1 of Savelieva does not teach a method of using the vector for treatment of diseases associated with the disorders of skin, hair and nails including transfection of cells of patient or animal organs and tissues with the DNA vector.
Mãnnik teaches methods of treatment with vectors for gene therapy including “coating with lipids or cell-surface receptors or transfecting agents” for patients or animals. Mãnnik also teaches KRT5, KRT14, LAMB3 and COL7A1 are target genes for Epidermolysis Bullosa Simplex (p. 46, line 19, p. 47, lines 25-27).
It would be obvious to one skilled in the art to combine the teachings of Savelieva and Mãnnik to create a method of treatment using the vector of Claim 15 by transfecting the Vtvaf17 based vector into animals or patients. One would have a reasonable expectation of success because Savelieva claims a vector for gene therapy, and Mãnnik provides guidance on how to administer gene vectors for therapy. Therefore, Claim 18 is obvious over Savelieva, Mãnnik, Vincze, and GenBank.
Allowable Subject Matter
The following art is cited below: Breitenbach, J. S., Human Gene Therapy, Vol. 26, p. A2-A108, October 2015.
Claim 17 and 18 are rejected under 35 USC 112(b) for being indefinite. Claim 15 and 18 are rejected on the rejected on the ground of nonstatutory double patenting. Claim 16 is rejected under 35 USC 112(d) for failing to limit Claim 15.
Regarding the prior art, a prior art search failed to reveal Vtvaf17. Mãnnik provides the closest prior art which teaches gene therapy using KRT5, KRT14, LAMB3, and COL7A1. Mãnnik does not teach Vtvaf17.
Regarding enablement, a prior art search and the instant specification revealed enabling literature for gene therapy using KRT5, KRT14, LAMB3, and COL7A1. The instant specification identifies clinical trials for gene therapy involving expression of COL7A1 (p. 3, lines 13-14) and LAMB3 (p. 4, lines 16-18). Breitenbach reports successful gene therapy expressing KRT14 and KRT5 in keratinocytes as well as patient derived keratinocytes xenografted on to mice (p. A44).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Krishna Nuggehalli Ravindra whose telephone number is (571)272-2758. The examiner can normally be reached M-Th, alternate F, 8a-5p est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.R./Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636