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 .
This action is in response to the papers filed on 07/12/2024. Claims 1-18 are currently pending.
Claims 1-18 are examined on their merits to which the following grounds of rejection are applicable. Claim 1 is an independent claim.
Priority
This application is a CON of 17/379,898 filed 07/19/2021 (granted US patent number 12070022) which claims benefit to CON of 15/923,951 filed 03/16/2018 (abandoned) which claims benefit to 14/698,561 filed 04/28/2015 (abandoned) which claims benefit of US provisional application 61/985,327 filed 04/28/2014.
Thus, the earliest possible priority for the instant application is 04/28/2014.
Claim Rejections - 35 USC § 112
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 1-18 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.
Claim 1 is incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. While all of the technical details of a method need not to be recited, the claims should include enough information to clearly and accurately describe the invention and how it is to be practice. The only disclosed step in claim 1 is providing a vertebrate cell which simultaneously comprises specific characteristics as disclosed in claim 1. However, the “wherein” clause in claim 1 is directed to edits in vertebrate cell in a first target chromosomal DNA site and a second target chromosomal site. It is not apparent what the method is for (i.e. no intended use is recited) that requires providing a vertebrate cell.
Claim 1 is vague and indefinite in the recitation “providing a vertebrate cell”. It is unclear if the cell is provided in vitro, in vivo, or ex vivo. As such the metes and bounds of the claim are indefinite.
Claim 2-18 inherent these deficiencies insofar as they depend from claim 1.
Claim 3 and 8 is vague and indefinite in the recitation of “functional factor” at line 15 and 3, respectively. The specification does not provide a definition for the phrase “functional factor” It is unknown what the phrase “functional factor” encompasses. The functional factor could be protein or mRNA and its prevented expression could be indirect or direct. As such the metes and bounds of the claim are indefinite.
Claim 4 inherent these deficiencies insofar as they depend from claim 3.
Claim 12 is vague and indefinite in the recitation of “the first homologous template and the second homologous template comprises the first edit or the second edit” at lines 17-18. It is unclear how the first homologous template and the second homologous template can comprise the first edit or the second edit, when the first edit or the second edit occur in the chromosomal DNA by the first homologous template and the second homologous template, according to claim 1. Clarification in the claim 12 is required. As such the metes and bounds of the claim are indefinite.
Claim 16 is vague and indefinite in the recitation of “is homozygous at least one of the first target chromosomal DNA site and the second target chromosomal DNA site and heterozygous at least one of the first target chromosomal DNA site and the second target chromosomal DNA site” at lines 1-4. It is unclear how it is possible for the first and second chromosomal DNA site to be heterozygous and homozygous simultaneously. Clarification in the claim 16 is required. As such the metes and bounds of the claim are indefinite.
Claim Interpretation
Claim 3 recites “a function factor”. The examiner is interpreting functional factor to mean any gene within the genome of a cell that has a function.
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)(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 1-18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Frendewey et al (US 20150159174 A1).
Regarding claim 1, Frendewey teaches methods for modifying a genomic locus of interest in a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences such that the method results in a cell which comprises Cas 9 endonuclease nucleic acid sequence, CRISPR RNA, LTVEC, and tracrRNA (i.e. an endonuclease system) (abstract, para 0005). Frendewey teaches a nucleic acid encoding a second expression construct guide RNA (gRNA) comprising a nucleotide sequence that hybridizes to a target sequence in the mammalian cell (i.e. is homologous to a target chromosomal DNA) (para 0005) and that the targeted genetic modification comprises: a replacement of an endogenous nucleic acid sequence with a homologous or an orthologous nucleic acid sequence; a deletion of an endogenous nucleic acid sequence, among other modifications listed (i.e. generating an edit in the target chromosomal DNA site) (para 0035). Frendewey teaches the method further comprises co-introducing a plurality of the second expression construct comprising distinct genomic target sequences into the mammalian cell for multiplex editing of distinct genomic loci (i.e. a first and second targeted endonuclease system with first and second homologous templates generating first and second edits) (para 0432). Frendewey teaches providing the cell from the disclosed method for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline (abstract). Thus, Frendewey anticipates:
A method comprising providing a vertebrate cell which simultaneously comprises:
a first targeted endonuclease system directed to a first target chromosomal DNA site in a genome of the vertebrate cell;
a first homologous template homologous to the first target chromosomal DNA site;
a second targeted endonuclease system directed to a second target chromosomal DNA site in the genome of the vertebrate cell;
a second homologous template homologous to the second target chromosomal DNA site,
wherein the first targeted endonuclease system and the first homologous template generate a first edit in the first target chromosomal DNA site,
and the second targeted endonuclease system and the second homologous template generate a second edit in the second target chromosomal DNA site.
Regarding claim 2, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches the targeted genetic modifications comprise a deletion of an endogenous nucleic acid sequence or insertion of an exogenous nucleic acid sequence (para 0013), or substitutions (para 0134), thus Frendewey anticipates wherein at least one of the first edit and the second edit comprises an insertion, a deletion, or a substitution.
Regarding claim 3, 5-8, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches the insert nucleic acid comprises a replacement of an endogenous rat, eukaryotic, non-rat eukaryotic, mammalian, human, rodent, non-rat rodent, mouse or hamster nucleic acid sequence with a homologous or an orthologous mammalian nucleic acid sequence, thus preventing expression of the gene (i.e. functional factor) (para 0301) by disrupting, removing, and altering a portion of the chromosomal DNA site. Hence, Frendewey anticipates wherein at least one of the first edit and the second edit prevents expression of a functional factor encoded by the first target chromosomal DNA site or the second target chromosomal DNA site, respectively, and comprises an insertion, deletion, or substitution of one or more bases in the first target chromosomal DNA site or the second target chromosomal DNA site (claim 3), wherein at least one of the first edit and the second edit disrupts the first target chromosomal DNA site or the second target chromosomal DNA site, respectively (claim 5), wherein the disruption occurs via removal of at least a portion of the first target chromosomal DNA site or the second target chromosomal DNA site (claim 6), wherein the disruption occurs via alteration of at least a portion of the first target chromosomal DNA site or the second target chromosomal DNA site (claim 7) and wherein the disruption prevents expression of a functional factor encoded by the first target chromosomal DNA site or the second target chromosomal DNA site (claim 8).
Regarding claim 4, the teachings of Frendewey anticipate claims 1 and 3. Moreover, Frendewey teaches “the genomic locus of interest can further comprise any component of a targeted integration system including, for example, a recognition site, a selection marker, a previously integrated insert nucleic acid, polynucleotides encoding nuclease agents, promoters” (para 0144) and “ the insert polynucleotide and the corresponding region of the rat, eukaryotic, non-rat eukaryotic, mammal, non-human mammal, human, rodent, non-rat rodent, mouse or hamster locus being replaced can be a coding region, an intron, an exon, an untranslated region, a regulatory region, a promoter, or an enhancer” (para 0313), thus Frendewey anticipates wherein the at least one of the first edit and the second edit is in a promoter or an enhancer.
Regarding claim 9, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches a large targeting vector (LTVEC) which comprises an insert nucleic acid that carries an exogenous nucleic acid (e.g., a homolog or ortholog of a rat nucleic acid), which is flanked by homologous arms, complementary to specific genomic regions, thus permitting replacement gene modifications (“the insert nucleic acid comprises a replacement of an endogenous rat, eukaryotic, non-rat eukaryotic, mammalian, human, rodent, non-rat rodent, mouse or hamster nucleic acid sequence with a homologous or an orthologous mammalian nucleic acid sequence, thus preventing expression of the gene” (para 0301), thus Frendewey anticipates wherein at least one of the first homologous template and the second homologous template encodes an exogenous allele for replacement of at least a portion of the first target chromosomal DNA site or the second target chromosomal DNA site, respectively.
Regarding claim 10, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches the method comprises introducing a plurality of the second construct and a plurality of the LTVEC for multiplex editing of distinct target loci as described herein thus Frendewey anticipates wherein a third, fourth, fifth, sixth, or seventh targeted endonuclease system directed to a third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively, and a third, fourth, fifth, sixth, or seventh homologous template homologous to the third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively, generate a third, fourth, fifth, sixth, or seventh edit at the third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively.
Regarding claim 11, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches “the LTVEC comprises an insert nucleic acid that can produce a deletion, addition, replacement or a combination thereof of a region of the rat, a eukaryotic, a non-rat eukaryotic, a mammalian, non-human mammalian, a human, a rodent, a non-rat rodent, a mouse or a hamster ApoE locus, the Il2rg locus, the Rag2 locus, the Rag1 locus and/or the Rag2/Rag1 locus” and generate an ApoE knockout, and Il2rg knockout, a Rag2 knockout, a Rag1 knockout, a Rag2/Rag1 knockout (para 0248), thus Frendewey anticipates wherein at least one of the first homologous template and the second homologous template encodes a knockout of a gene encoded by the first target chromosomal DNA site or the second target chromosomal DNA site, respectively.
Regarding claim 12, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches “the LTVEC comprises an insert nucleic acid that can produce a deletion, addition, replacement or a combination thereof of a region of the rat, a eukaryotic, a non-rat eukaryotic, a mammalian, non-human mammalian, a human, a rodent, a non-rat rodent, a mouse or a hamster ApoE locus, the Il2rg locus, the Rag2 locus, the Rag1 locus and/or the Rag2/Rag1 locus” (para 0248), thus Frendewey anticipates wherein at least one of the first homologous template and the second homologous template comprises the first edit or the second edit, respectively.
Regarding claim 13, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches the nucleic acid integrated at the target locus can comprise a sequence for a polynucleotide of interest from a different species than the cell it is introduced into (para 0380), thus Frendewey anticipates wherein the vertebrate cell is from a first species or a first breed of livestock and at least one of the first edit and the second edit comprises a replacement of a native allele with an exogenous allele from a second species or a second breed of livestock.
Regarding claim 14, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches “The biallelic targeted genetic modification at the target locus can result in a homozygous genetically modified cell.” (para 0346), thus Frendewey anticipates wherein the vertebrate cell is homozygous at at least one of the first target chromosomal DNA site and the second target chromosomal DNA site.
Regarding claim 15, the teachings of Frendewey anticipateclaim 1. Moreover, Frendewey teaches “the targeted genome modification creates a modified pluripotent cell that is compound heterozygous at the genomic locus of interest” (para 0448), thus Frendewey anticipates wherein the vertebrate cell is heterozygous at at least one of the first target chromosomal DNA site and the second target chromosomal DNA site.
Regarding claim 16, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches “The biallelic targeted genetic modification at the target locus can result in a homozygous genetically modified cell.” (para 0346) and “the targeted genome modification creates a modified pluripotent cell that is compound heterozygous at the genomic locus of interest” (para 0448), thus Frendewey anticipates wherein the vertebrate cell is homozygous at at least one of the first target chromosomal DNA site and the second target chromosomal DNA site and heterozygous at at least one of the first target chromosomal DNA site and the second target chromosomal DNA site.
Regarding claim 18, the teachings of Frendewey anticipate claim 1. Moreover, Frendewey teaches the cell is a mammalian cell, a fibroblast, a pluripotent cell, a non-human pluripotent cell, a rodent pluripotent cell, a mouse or rat embryonic stem (ES) cell, a human pluripotent cell, a human embryonic stem (ES) cell, a human adult stem cell, a developmentally restricted human progenitor cell, or a human induced pluripotent stem (iPS) cell (para 0032), thus Frendewey anticipates wherein the vertebrate cell is selected from the group consisting of:a zygote, a stem cell, an adult stem cell, a pluripotent cell, a progenitor cell, and a primary cell.
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.
Claim 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 2, 4-8, 10, 12, and 13 of U.S. Patent No. 12070022 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of U.S. Patent No. 12070022 B2.
Claim 1 of U.S. Patent No. 12070022 B2 teaches a method of making gene edits in vitro in a non-human vertebrate cell at two or more gene loci, the method comprising a simultaneous step of introducing into a non-human vertebrate cell:
a first targeted CRISPR endonuclease system directed to a first target chromosomal DNA site in a genome of the non-human vertebrate cell,
a first homology directed repair template homologous to a single gene locus in the first target chromosomal DNA site,
a second targeted CRISPR endonuclease system directed to a second target chromosomal DNA site in the genome of the non-human vertebrate cell,
and a second homology directed repair template homologous to a single gene locus in the second target chromosomal DNA site,
wherein the first homology directed repair template sequence independently replaces a native chromosomal DNA sequence at the single gene locus in the first target chromosomal DNA site in the genome of the non-human vertebrate cell and the second homology directed repair template sequence independently replaces a native chromosomal DNA sequence at the single gene locus in the second target chromosomal DNA site in the genome of the non-human vertebrate cell;
wherein the first target chromosomal DNA site is in a first gene and the second target chromosomal DNA site is in a second gene; thereby making a non-human vertebrate cell comprising gene edits at two or more gene loci.
Claim 2 of U.S. Patent No. 12070022 B2 teaches “The method of claim 1 further comprising introducing into the non-human vertebrate cell one or more of: a third, fourth, fifth, sixth, or seventh targeted CRISPR endonuclease system directed to a third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively, and a third, fourth, fifth, sixth, or seventh homology directed repair template homologous to a single gene locus in each of the third, fourth, fifth, sixth, or seventh target chromosomal DNA sites, respectively.”
The instant application is drawn to a method comprising providing a vertebrate cell which simultaneously comprises:
a first targeted endonuclease system directed to a first target chromosomal DNA site in a genome of the vertebrate cell,
a first homologous template homologous to the first target chromosomal DNA site, a second targeted endonuclease system directed to a second target chromosomal DNA site in the genome of the vertebrate cell,
and a second homologous template homologous to the second target chromosomal DNA site,
wherein the first targeted endonuclease system and the first homologous template generate a first edit in the first target chromosomal DNA site
and the second targeted endonuclease system and the second homologous template generate a second edit in the second target chromosomal DNA site (claim 1);
And the method of claim 1, wherein a third, fourth, fifth, sixth, or seventh targeted endonuclease system directed to a third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively, and a third, fourth, fifth, sixth, or seventh homologous template homologous to the third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively, generate a third, fourth, fifth, sixth, or seventh edit at the third, fourth, fifth, sixth, or seventh target chromosomal DNA site, respectively (claim 10).
The instant claims differ in that they recite a method of comprising providing a vertebrate cell.
However, the claims of U.S. Patent No. 12070022 B2 recite that the method is specifically for making gene edits in vitro in a non-human vertebrate cell comprising the use of non-human vertebrate cell, which reads on the broad method of instant claim 1 comprising providing a vertebrate cell in which in the vertebrate cell comprises characteristics that read on the cell characteristics of U.S. Patent No. 12070022 B2. Therefore, the claims of U.S. Patent No. 12070022 B2 render obvious the claims of the instant application.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights