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 .
Application Status
The Amendments and Remarks filed 11 September 2023 are acknowledged and have been entered. Claims 1-76 are cancelled. Claims 77-95 are newly added. Claims 77-95 are pending and being examined on the merits.
Priority
This application is a continuation of application 15/737,132 filed 12/15/2017 which is a 371 PCT of application US2016/038161 filed 06/17/2016 which claims priority to application 62/266,316 filed 12/11/2015 and 62/181,138 filed 06/17/2015.
Information Disclosure Statement
The information disclosure statement filed 06/17/2015 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 30 and 57. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term LSRFortessa, PrimeStar, Trizol, Covaris, NEBNext, Ultra, Illumina, Kapa, Applied Biosystems, ViiA, Life Technologies, Illumina TruSeq PE Cluster Kit, TruSeq, Illumina HiSeq 2500, to name a few,which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. A cursory review of the specification has revealed these trade names or marks. It would be remedial to identify and amend all trade names or marks in the specification upon amendment.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 77-79 and 81-95 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.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 77 recite “A complex for editing the genome of a T cell progenitor cell comprising: … a recombinant site-directed nuclease operably linked to a superpositively charged protein, wherein the site-directed nuclease comprises an RNA-binding portion that interacts with the second nucleotide sequence of the guide RNA and wherein the site-directed nuclease specifically binds and cleaves the target DNA to create a double stranded break”. These claims require the provision of a genus of site-directed nucleases defined solely by the function of capable of being guided by an RNA to cleave the target DNA to create a double stranded break.
The specification envisions using ‘a Cas protein from any bacterial species or a functional fragment thereof. For example, the Cas protein can be a Cas9 protein or a functional fragment thereof’ [pg. 10, lines 11-27].
Koonin (Koonin et al. 2017. Current Opinion in Microbiology, 37-67-78) who illustrates that there was not a common structural characteristic that was in common among different Cas endonucleases (see Table 1). This is reiterated by Koonin who teaches that “the other parts of the Cas9 and Cas12 (the new designation for the type V effectors) proteins from different subtypes show no similarity to one another at the sequence or structure levels” (page 71, column 2, last paragraph). Accordingly, Koonin supports the conclusion that there was a high degree of variation among different members of Cas endonucleases such that the structure of one member of the genus is not predictable based upon the structure of other members of the genus.
Josephs (Josephs et al. Nucleic Acids Research, Vol. 43, No. 18, pages 8924-8941, September 17, 2015) teach that Cas9 is an RNA-guided endonuclease that cleaves both strands of a target DNA (e.g., Title; Abstract; Fig. 1). Zetsche (Zetsche et al. Cell, Vol. 163, pages 759-771, September 25, 2015) teach that Cpf1 is an RNA-guided DNA endonuclease that cleaves both strands of DNA to create a staggered DNA double-strand break (e.g., Title; Abstract). Therefore, the skilled artisan would have understood that it would have been unpredictable to extrapolate the results from the specific site-directed nuclease tested in the instant disclosure to all possible site-directed nucleases.
Accordingly, in view of the limited amount of guidance provided by the specification and the art and the unpredictability of the art, one of ordinary skill in the art would conclude that Applicant was not in possession of using “any” site-directed nuclease to induce a double stranded break in a target DNA.
Claims 77-79 and 81-95 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for compositions comprising and methods of using a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) nickase selected from the groups consisting of a Cas9 according to prior art methods, does not reasonably provide enablement for other CRISPR-Cas nickases, wild-type CRISPR-Cas nickases or nucleases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claim 77 is drawn to “A complex for editing the genome of a T cell progenitor cell comprising: a. a guide RNA (gRNA) comprising a first nucleotide sequence that hybridizes to a target DNA in the genome of the T cell progenitor cell, wherein the target DNA comprises the mutation, and a second nucleotide sequence that interacts with a site-directed nuclease; b. a recombinant site-directed nuclease operably linked to a superpositively charged protein, wherein the site-directed nuclease comprises an RNA-binding portion that interacts with the second nucleotide sequence of the guide RNA and wherein the site-directed nuclease specifically binds and cleaves the target DNA to create a double stranded break; and c. a single-stranded donor oligonucleotide (ssODN) that hybridizes to a genomic sequence flanking the double stranded break in the target DNA and integrates into the target DNA to edit the target DNA”. Claim 89 is drawn to a “A method of editing a population of T cell progenitor cells comprising introducing into the T cell progenitor cells the complex of claim 77.
Breadth of the claims: The claims broadly encompass the provision or use of any site-directed nuclease or any RNA-guided DNA nuclease. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
\Guidance of the specification: The specification envisions using ‘a Cas protein from any bacterial species or a functional fragment thereof. For example, the Cas protein can be a Cas9 protein or a functional fragment thereof’ [pg. 10, lines 11-27].
Predictability and state of the art: Koonin (Koonin et al. 2017. Current Opinion in Microbiology, 37-67-78) who illustrates that there was not a common structural characteristic that was in common among different Cas endonucleases (see Table 1). This is reiterated by Koonin who teaches that “the other parts of the Cas9 and Cas12 (the new designation for the type V effectors) proteins from different subtypes show no similarity to one another at the sequence or structure levels” (page 71, column 2, last paragraph). Accordingly, Koonin supports the conclusion that there was a high degree of variation among different members of Cas endonucleases such that the structure of one member of the genus is not predictable based upon the structure of other members of the genus.
Josephs (Josephs et al. Nucleic Acids Research, Vol. 43, No. 18, pages 8924-8941, September 17, 2015) teach that Cas9 is an RNA-guided endonuclease that cleaves both strands of a target DNA (e.g., Title; Abstract; Fig. 1). Zetsche (Zetsche et al. Cell, Vol. 163, pages 759-771, September 25, 2015) teach that Cpf1 is an RNA-guided DNA endonuclease that cleaves both strands of DNA to create a staggered DNA double-strand break (e.g., Title; Abstract). Therefore, the skilled artisan would have understood that it would have been unpredictable to extrapolate the results from the specific site-directed nuclease tested in the instant disclosure to all possible site-directed nucleases.
Amount of experimentation necessary: A large amount of experimentation would be required to make and use the full scope of the claimed invention. One would be required to identify each and every site directed nuclease function, or fraction thereof, to create a double stranded break in a target DNA. This type of experimentation would require a large amount of inventive effort.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 36-39 are not considered to be fully enabled by the instant disclosure.
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 77-95 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 77 recites the limitation "the mutation" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 77-80, 82, 86-88, 89-90, and 92-93 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Musunuru (US 2015/0152436 A1, published 6/4/2015).
Regarding claim 77-79, 82, and 88-90, Musunuru teaches a method for treating or preventing a disorder associated with expression of SCD-associated polynucleotide sequences in a subject, the method comprising altering target SCD-associated polynucleotide sequences in a cell by contacting the SCD-associated polynucleotide sequences with a clustered regularly interspaced short palindromic repeats-associated (Cas) protein and multiple ribonucleic acids, wherein the ribonucleic acids direct Cas protein to and hybridize to target moieties of the target SCD associated polynucleotide sequences, and wherein the target SCD-associated polynucleotide sequences are cleaved, thereby treating or preventing a disorder associated with expression of the SCD-associated polynucleotide sequences [0015]. Musunuru teaches that the target polynucleotide sequence is cleaved such that a double-strand break results. Musunuru teaches the alteration results in correction of the target polynucleotide sequence from an undesired sequence to a desired sequence [0026]. Musunuru teaches that subsequent to cleavage of the target polynucleotide sequence, homology-directed repair occurs, is performed using an exogenously introduced DNA repair template that is single stranded [0027]. Musunuru teaches that DNA repair template can be designed to repair or replace any target polynucleotide sequence, particularly target polynucleotide sequences comprising disease associated polymorphisms (e.g., SNPs), and the homology-directed repair of a mutant allele comprising such SNPs can be achieved with a CRISPR/Cas system by selecting two target motifs which flank the mutant allele, and an designing a DNA repair template to match the wild-type allele. Musunuru teaches that the cell is a hematopoietic stem cell (i.e. a T cell progenitor cell) [0028]. Musunuru teaches that SCD-associated polynucleotide sequence is used to refer to a polynucleotide sequence of the HBB gene displaying one or more HBB mutations associated with SCD [0155]. Musunuru teaches that Cas proteins can be conjugated to or fused to a charged protein ( e.g., that carries a positive, negative or overall neutral electric charge) such as a superpositively charged GFP to significantly increase the ability of the Cas protein to penetrate a cell [0251].
Regrading claims 80, Musunuru teaches that the Cas protein is Streptococcus
pyogenes Cas9 protein or a functional portion thereof [0022].
Regarding claims 86-87 and 92-93, Musunuru teaches where more than 5% of the population of T cells comprised the correct mutation [Table T6, Fig. 17].
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 77-83, 86-90, and 92-95 are rejected under 35 U.S.C. 103 as being unpatentable over Musunuru (US 2015/0152436 A1, published 6/4/2015) in view of Cronican (Cronican et al. Vol.5 No.8. Acs Chemical Biology. 2010).
Regarding claim 77-79, 82, and 88-90, Musunuru teaches a method for treating or preventing a disorder associated with expression of SCD-associated polynucleotide sequences in a subject, the method comprising altering target SCD-associated polynucleotide sequences in a cell by contacting the SCD-associated polynucleotide sequences with a clustered regularly interspaced short palindromic repeats-associated (Cas) protein and multiple ribonucleic acids, wherein the ribonucleic acids direct Cas protein to and hybridize to target moieties of the target SCD associated polynucleotide sequences, and wherein the target SCD-associated polynucleotide sequences are cleaved, thereby treating or preventing a disorder associated with expression of the SCD-associated polynucleotide sequences [0015]. Musunuru teaches that the target polynucleotide sequence is cleaved such that a double-strand break results. Musunuru teaches the alteration results in correction of the target polynucleotide sequence from an undesired sequence to a desired sequence [0026]. Musunuru teaches that subsequent to cleavage of the target polynucleotide sequence, homology-directed repair occurs, is performed using an exogenously introduced DNA repair template that is single stranded [0027]. Musunuru teaches that DNA repair template can be designed to repair or replace any target polynucleotide sequence, particularly target polynucleotide sequences comprising disease associated polymorphisms (e.g., SNPs), and the homology-directed repair of a mutant allele comprising such SNPs can be achieved with a CRISPR/Cas system by selecting two target motifs which flank the mutant allele, and an designing a DNA repair template to match the wild-type allele. Musunuru teaches that the cell is a hematopoietic stem cell (i.e. a T cell progenitor cell) [0028]. Musunuru teaches that SCD-associated polynucleotide sequence is used to refer to a polynucleotide sequence of the HBB gene displaying one or more HBB mutations associated with SCD [0155]. Musunuru teaches that Cas proteins can be conjugated to or fused to a charged protein ( e.g., that carries a positive, negative or overall neutral electric charge) such as a superpositively charged GFP to significantly increase the ability of the Cas protein to penetrate a cell [0251].
Regrading claims 80, Musunuru teaches that the Cas protein is Streptococcus pyogenes Cas9 protein or a functional portion thereof [0022].
Regarding claims 81 and 83, Musunuru is silent in regards to the supercharged protein being a superpositively charged +36 GFP.
Cronican teaches superpositive GFPs are able to form stable noncovalent complexes with nucleic acids and that +36 GFP can deliver siRNA and plasmid DNA into a variety of mammalian cell lines without apparent cytotoxicity [pg. 747, col. 2. para 1].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the complex and method of Musunuru where the supercharged protein fused to Cas9 is a superpositively charged +36 GFP. One of ordinary skill would be motivated to make the modification for the advantage of delivering the Cas9 to cells without causing cellular cytotoxicity.
Regarding claim 84, the claim recites “The complex of claim 77, wherein the molar ratio of gRNA to site-directed nuclease operably linked to a supercharged protein to ssODN is from about 1:1:0.2 to about 1.5:1:2.0. Musunuru is silent on such a range of ratios, but it is prima facie obvious to optimize within prior art ranges. See M.P.E.P. § 2144.05(II): “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
Regarding claims 85, and 94-95, Musunuru teaches the period of viability of the cells after administration to a subject can be as short as a few hours, e.g. twenty-four hours, to a few days, to as long as several years. Thereby one of ordinary skill would be motivated to make the complex and practice the claimed method with the expectation that the survival rate for the edited or correct cells is at least 50% given Musunuru’s teaching that the cells can be viable as long as several years.
Regarding claims 86-87 and 92-93, Musunuru teaches where more than 5% of the population of T cells comprised the correct mutation [Table T6, Fig. 17]. Munsunuru teaches that the efficiency of alteration of cells that express Cas protein is from about 50% to about 80% [0311].
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: Claim 91 is free of the art. Claim 91 recites “wherein the ratio of homology-directed repair to nonhomologous end joining (NHEJ) in the population of cells is from about 10 to about 0.5”. The closest prior art is Musunuru as discussed above. Musunuru is slient regarding the ratio of HDR to NEHJ. Lin teaches that cells have differing abilities to repair DSBs using NHEJ or HDR as NHEJ dominates DNA repair during G1, S and G2 phases, whereas HDR is restricted to late S and G2 phases when DNA replication is completed and sister chromatids are available to serve as repair templates [pg. 1, last paragraph]. Lin teaches that chemical or genetic interruption of the NHEJ pathway can favor HDR [pg. 1, last paragraph], and report that cell cycle synchronization techniques with direct nucleofection of pre-assembled Cas9 ribonucleoprotein (RNP) complexes achieve controlled nuclease action at the phase of the cell cycle best for HDR and enhance HDR efficiency in human cells [pg. 2, first paragraph]. Therefore it would have not been obvious that the method as claimed would have increased HDR 20 fold.
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 77-95 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 7-10 and 12-15 of U.S. Patent No. 11643668. Although the claims at issue are not identical, they are not patentably distinct from each other because the U.S. Patent claims A complex for correcting a mutation associated with sickle cell anemia in the genome of a CD34+ human stem/progenitor cell (HSPC) comprising: a. a guide RNA (gRNA) comprising a first nucleotide sequence that hybridizes to a target DNA in the genome of the CD34+ HSPC, wherein the target DNA comprises the mutation associated with sickle cell anemia, and a second nucleotide sequence that interacts with a site-directed nuclease; b. a recombinant site-directed nuclease operably linked to a superpositively charged protein, wherein the site-directed nuclease comprises an RNA-binding portion that interacts with the second nucleotide sequence of the guide RNA and wherein the site-directed nuclease specifically binds and cleaves the target DNA to create a double stranded break, wherein the superpositively charged protein is a superpositively charged green fluorescent protein (GFP) that has an overall positive charge from about +5 to about +40, and wherein the superpositively charged protein is operably linked to the carboxy-terminus of the site-directed nuclease; and c. a single-stranded donor oligonucleotide (ssODN) that hybridizes to a genomic sequence flanking the double stranded break in the target DNA and integrates into the target DNA to correct mutation associated with sickle cell anemia in the target DNA.
Claims 77-95 are anticipated by the patented claims.
Claims 77-95 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 6 of U.S. Patent No. 11555207B2 in view of Musunuru (US 2015/0152436 A1, published 6/4/2015) in view of Cronican (Cronican et al. Vol.5 No.8. Acs Chemical Biology. 2010) . Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the U.S. patent claims method of making tumor-specific T-cell precursor cells comprising introducing into a population of T-cell precursor cells a complex comprising: a. a guide RNA (gRNA) comprising a first nucleotide sequence that hybridizes to a target DNA in the genome of the T cell precursor cells and a second nucleotide sequence that interacts with a CRISPR-Cas9 nuclease; b. a recombinant CRISPR-Cas9 nuclease operably linked to a superpositively charged protein, wherein the CRISPR-Cas9 nuclease comprises an RNA-binding portion that interacts with the second nucleotide sequence of the gRNA, wherein the CRISPR-Cas9 nuclease specifically binds and cleaves the target DNA to create a double stranded break, wherein the positively supercharged protein is a superpositively charged green fluorescent protein (GFP) that has an overall positive charge from about +5 to about +40, and wherein the superpositively charged protein is operably linked to the carboxy-terminus of the CRISPR-Cas9 nuclease; and c. a donor nucleic acid sequence comprising a third nucleotide sequence that encodes a chimeric antigen receptor (CAR) and a fourth nucleotide sequence that hybridizes to a genomic sequence flanking the double stranded break in the target DNA, wherein the complex is introduced into the T-cell precursor cells, by nucleoporation, under conditions that allow homology-directed repair (HDR) and integration of the third nucleotide sequence into the target DNA to form modified T-cell precursor cells that express the CAR, and wherein the ratio of homology-directed repair to nonhomologous end joining in the population of T-cell precursor cells is at least 0.5.
The U.S. Patent does not claim where the complex corrects a mutation in the target DNA. The teachings of Musunuru are discussed above. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to design the complex of the U.S. Patent to correct a mutation in the genome of a cell. One of ordinary skill would be motivated to make the modification with a reasonable expectation of success because Musunuru teaches that a complex comprising a gRNA, Cas9, and ssODN can be used for the correction of genetic mutations.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Musunuru and Cronican are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
Conclusion
No claims allowed.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637