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 .
Withdrawn Rejection
The rejection of claim(s) 1, under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zivin (US2007/0266449 A1 pub date:12/15/2007; effectively filed:5/12/2006), is withdrawn. The claims as amended required the cell to be a bovine fibroblast cell or a cell derived from a bovine fibroblast. Zivin does not disclose this new limitation.
The rejection of claim(s) 1, under 35 U.S.C. 102(a)(2) as being anticipated by Voytas (US 2011/0145940 effectively filed 12/10/2009), is withdrawn. The claims as amended required the cell to be a bovine fibroblast cell or a cell derived from a bovine fibroblast. Voytas does not disclose this new limitation.
All of the double patenting rejections of record are being withdrawn because they do not recite a bovine fibroblast cell or a cell derived from a bovine fibroblast as the amendment claims now require.
The following new rejections are necessitated by the amendments to the claims:
Claim Rejections - 35 USC § 112-New Matter
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.
Claim 1 is 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.
When determining if a newly added recitation has adequate written description, the specification and claims, as originally filed, are examined to determine if one of explicit or implicit description for the new recitation is present.
The claim new recites, “the animal cell is….derived from a bovine fibroblast”.
A search of the specification fails to provide any literal recitation of “derived from a bovine fibroblast”. As such, the specification and claims, as originally filed, fail to provide an explicit description of the above new recitation.
A review of the specification found many references to bovine fibroblasts, cattle fibroblast, and fibroblast derived from horned dairy bulls (see [0080] and [0335] for example). However, the specification does not derive any types of animal cells that are “derived from a bovine fibroblast”. The only type of cell Examiner could think of the may be a cell derived from a bovine fibroblast is an induced pluripotent stem cells or a cell transdifferentiated from a bovine fibroblast. However, the specification fails to provide any description of reprogramming bovine fibroblast to any type of new cell type. As such, Examiner could find any type of description in the originally filed specification and claims that would be considered an example of a cell derived from a bovine fibroblast. As such, the original specification and claims also fail to provide an implicit description for the above new recitation.
Examiner looked to Applicant remarks to determine where Applicant believes there is written support for “derived from a bovine fibroblast”. The remarks state, “Support for the claim amendment is found throughout the as-filed application.” However, not such support was found and Applicant did not provide specific evidence by citations from the originally filed specification to demonstrate adequate written description. As such, the newly added recitation of “derived from a bovine fibroblast” constitutes new matter because neither the originally filed specification nor claims provide explicit or implicit support for it.
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.
(1) Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zivin (US2007/0266449 A1 pub date:12/15/2007; effectively filed:5/12/2006) in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Zivin teaches a method for generating an animal cell containing an endogenous protein that has been modified in at least one region to match its human homologue, comprising the steps of: a) identifying at least one region in an animal protein that differs from a corresponding human protein homologue; b) determining the nucleotide sequences that encodes the region of difference in the human and animal genes; c) identifying a target locus for a zinc finger nuclease within the identified region of difference in the animal gene; d) determining the nucleotide sequences that flank the region of difference in the animal gene; e) generating donor DNA, comprising an oligonucleotide that encodes the human region of difference, flanked by the sequences determined in step d; f) generating a zinc finger nuclease that is capable of binding to the target locus; g) introducing the donor DNA and the zinc finger nuclease into animal cells, thereby inducing double-stranded breaks in the DNA of the animal cells, h) allowing homologous recombination to occur between the animal DNA and the donor DNA, and; i) selecting the animal cells where homologous recombination has occurred. See page 7, claim 6.
Zivin generically teaches animal cells as discussed above. However, Zivin does not teach bovine fibroblast cells or derived from a bovine fibroblast as the amendment now requires. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an animal cell taught by Zivin to predictably arrive at the limitations of claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of Zivin because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, Zivin in view of You render claim 1 obvious.
(2) Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voytas (US 2011/0145940 effectively filed 12/10/2009) in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Voytas teaches a method for modifying the genetic material of a cell, comprising: (a) providing a cell containing a target DNA sequence; and (b) introducing a transcription activator-like (TAL) effector-DNA modifying enzyme into the cell, the TAL effector-DNA modifying enzyme comprising: (i) a DNA modifying enzyme domain that can modify double stranded DNA, and (ii) a TAL effector domain comprising a plurality of TAL effector repeat sequences that, in combination, bind to a specific nucleotide sequence in the target DNA sequence, such that the TAL effector-DNA modifying enzyme modifies the target DNA within or adjacent to the specific nucleotide sequence in the cell or progeny thereof (claim 1). The method of claim 1, wherein the cell is a mammalian cell (claim 4). See page 136.
Voyas generically teaches mammalian animal cells as discussed above. However, Voyas does not teach bovine fibroblast cells or derived from a bovine fibroblast as the amendment now requires. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an animal cell taught by Voyas to predictably arrive at the limitations of claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of Voyas because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, Voyas in view of You render claim 1 obvious.
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.
(1) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,920,242 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 recites, a method of genetically modifying an isolated bovine cell (i.e. altering the genome of an animal cell) in which a horned gene sequence of the isolated bovine cell is edited to a polled gene sequence (i.e. identifying a target DNA region within the animal cell, the target region comprising a target cleavage site), the method comprising: introducing to the isolated bovine cell a transcription activator-like effector nuclease (TALEN) that specifically binds and cleaves a target DNA sequence in the horned gene sequence of said bovine cell (i.e. contacting the animal cell with a targeted nuclease as claimed) ; and introducing into the isolated bovine cell an HDR template that comprises at least a portion of the polled gene sequence flanked by sequences homologous to the target DNA site, wherein the horned gene sequence is converted into a polled gene sequence.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
(2) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,959414 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 discloses a method comprising: (a) introducing into a cell isolated from a non-human animal line (i) a CRISPR/Cas9 endonuclease; (ii) a guide RNA (gRNA) comprising a spacer RNA sequence that interacts with a target sequence in the chromosomal DNA of the cell; wherein said introducing step (a) results in cleavage of the chromosomal DNA at the target sequence in the cell. Thus the patent claim discloses a species of the instant claim.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
(3) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9528124 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 recites a method of introgressing an allele or gene into chromosomal DNA of a non-human animal cell comprising: introducing into a cell isolated from a non-human animal line (i) a CRISPR/Cas endonuclease, (ii) a guide RNA (gRNA) comprising a spacer RNA sequence that interacts with a target sequence in the chromosomal DNA of the cell, and (iii) a homology-directed repair (HDR) template DNA sequence encoding an allele or a gene flanked by sequences homologous to the target sequence in a chromosomal DNA of the cell, wherein said introducing alters the chromosomal DNA of the cell to have identity with the HDR template DNA sequence at the target sequence in the chromosomal DNA, thereby introgressing the allele or the gene into the chromosomal DNA of the cell, wherein the HDR template DNA sequence also comprises a DNA sequence encoding a mismatch in the target sequence that alters the interaction with the RNA spacer sequence of the gRNA, and wherein the mismatch is introduced into the chromosomal DNA of the cell and creates a sequence in the chromosomal DNA of the cell that is not found in the non-human animal line.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
(4) Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending Application No. 18771458 (reference application) in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Copending claim 17 introduces multiple targeting endonuclease systems to a vertebrate cell to alter the target sites. Claim 17 specifies that the vertebrate cells are from human, simian, dog, cat, bird, fish, rabbit, pig, cattle, buffalo, goat, sheep, or artiodactyl (i.e. animal cells).
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in copending claim 17 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of copending claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, copending claim 1 in view of You renders instant claim 1 obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(5) Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17933367 (reference application) in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Copending claim 1 discloses a method of replacing an endogenous allele with an exogenous allele in a non-human animal cell (i.e. a method of altering the genome of an animal cell) comprising introducing into the cell (i.e. contact the cell as claimed) (i) a targeted endonuclease system comprising a DNA binding member comprising a DNA-binding sequence wherein the DNA binding sequences binds a target (i.e. identifying a target DNA region within the animal cell, the target region comprising target cleavage site).
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in copending claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of copending claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, copending claim 1 in view of You renders instant claim 1 obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(6) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,893,667 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 discloses (a) providing (i) a cell or embryo from a livestock animal of a first livestock breed, wherein the cell or embryo comprises in its genome a first allele of a gene, (ii) a TALEN that specifically binds to and cleaves DNA at a specific site in the first allele of the gene, (b) introducing the TALEN and the HDR template into the cell or embryo, wherein the TALEN creates a double-stranded break in the specific site and the HDR template inserts into the double-stranded break, thereby inserting the second allele of the gene into the genome of the cell or embryo, thereby replacing the first allele of the gene with the second allele of the gene.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
(7) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,477,969 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 the method comprising: (a) introducing into a cell isolated from a non-human animal line (i) a CRISPR/Cas9 endonuclease; (ii) a guide RNA (gRNA) comprising a spacer RNA sequence that interacts with a target sequence in the chromosomal DNA of the cell; wherein said introducing step (a) results in cleavage of the chromosomal DNA at the target sequence in the cell.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
(8) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 10,058,078 in further view of You (You et al. Mol. Cells 18(2):261-268, 2004).
Patent claim 1 discloses the method comprising the steps of: (a) introducing into a pig fibroblast (i) a TALEN pair that specifically binds to the endogenous eIF4GI gene and causes a double-stranded DNA break to inactivate the eIF4GI gene in the pig fibroblast.
Patent claim 1 does not recite that the cell are bovine fibroblast. However, You teaches that although primary bovine embryonic fibroblast (BEF) cells have previously been used as nucleus-donors for nuclear transfer (NT), it has now been proposed to use BEF cells to generate cloned cows that were genetically modified by transgenic or a knock-out system. Two life-span extended BEF cell lines (designated CGFR-BO-1 and CGFR-BO-2) were shown to grow much faster than their parental primary counterparts. In cloning experiments using these cell lines as a nuclear donor, the reconstructed karyoblasts underwent apoptosis, reprogramming and development in the blastocyst stage, at a similar frequency to those observed with parental as well as adult primary fibroblasts. Furthermore, these cell lines targeted with green fluorescence protein (GFP) were successfully transduced, selected and reprogrammed by NT to develop into a blastocyst stage with GFP expression. Our results suggested methods to extend life-span of donor cells with tremendous implications for the genetic engineering of bovine fibroblast cells. (p. 261, abstract).
Thus, it would have been to an artisan of ordinary skill before the time of effectively filing to use the BEF cell line taught by You in the method of genetically modifying an bovine cell taught in patent claim 1 to predictably arrive at the limitations of instant claim 1. An artisan would have a reasonable expectation of success because You teaches that their BEF are successfully transfected, genetically modified, and capable of forming NT blastocysts. Further an artisan would have been motivated to use the BEF cell line of You with the method of patent claim 1 because You teaches a desire to you bovine fibroblast as the donor cell for transgenic or knock-out system to make genetically modified bovine blastocysts and ultimately bovine animals. As such, patent claim 1 in view of You renders instant claim 1 obvious.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632