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 .
Applicant’s amendments to the claims 4/13/23 are acknowledged. Claims 1-47 are cancelled. Claims 48-60 are new. Prosecution on the merits commences for claims 48-60.
PRIORITY
The instant Application, filed 12/30/2022, is a DIVISIONAL of US Patent No. 11,572,543, filed, 11/08/2017, which is a 371 of PCT/US2016/031224 filed 05/06/2016, which claims priority to US provisional Application No. 62/158,882. Thus, the earliest possible priority for the instant Application is 05/08/2015.
CLAIMS
Claim 48 is broadly directed to a method of producing an isolated genetically engineered human cell with reduced BCL11A mRNA or BCL11A protein expression, comprising the use of CRISPR gene-editing technology. Claim 48, of record 4/13/23, is presented below:
A method for producing an isolated genetic engineered human cell having decreased
BCL11A mRNA or protein expression, the method comprising expressing in a cell:
a. a vector for gene editing comprising
i) a protospacer adjacent motif (PAM) sequence;
ii) a trans-activating CRISPR RNA (tracrRNA) sequence; and
ii) a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1-94, and
b. at least a DNA-targeting endonuclease in an isolated human cell,
whereby the DNA-targeting endonuclease cleaves the genomic DNA of the cell on chromosome 2 at location 60725424 to 60725688 (+55 functional region), at location 60722238 to 60722466 (+58 functional region), and/or at location 60718042 to 60718186 (+62 functional region), causing at least one genetic modification therein, wherein the human chromosome 2 is that according to UCSC Genome Browser hg 19 human genome assembly.
Claim Objections
Claims 48, 50, 52, and 55-60 are objected to because of the following informalities:
Claim 48 utilizes subsections “a.” and “b.” which is improper for using periods within the claims. While there is no set statutory form for claims, the present Office practice is to insist that each claim begin with a capital letter and end with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). See M.P.E.P. § 608.01(m).
Claims 48, 56, 57: The claims recite an “isolated genetic engineered human cell” which should be amended to an “isolated genetically engineered human cell” throughout.
Claim 50 should be amended to recite: “The method of claim 49, wherein the Cas protein…”
Claim 52 should recite, “or an adeno-associated virus.”
Claim 55 should recite, “the vector for gene editing and the
Claim 56 should be amended to recite “produced according to the method of claim 48” at line 4.
Claim 57 should be amended to recite, “A composition comprising the isolated genetically engineered human cells of claim 56.”
Claim 58 should be amended to recite “A method of increasing fetal hemoglobin levels in a cell, the method comprising decreasing the BCL11A mRNA or BCL11A protein expression in an isolated genetically engineered human cell produced according to the method claim 48.”
Claim 59 should be amended to recite, “wherein the isolated genetically engineered human cell is an embryonic stem cell, a somatic stem cell, a progenitor cell, a bone marrow cell, a hematopoietic progenitor cell or a hematopoietic stem cell.”
Claim 60 should be amended to recite, “transplanting [[a]] the composition of claim” in line 2.
Appropriate correction is required.
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 48-60 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.
Claims 48 and 56 are indefinite for the use of parentheticals (+55 functional region), (+58 functional region) and (+62 functional region). It is not clear from the specification or the claims if the language within the parentheticals is an example or a definition? See MPEP 2173.05(d). It is not clear if the location is defined by the base pair location or the term within the parenthesis?
Claim 48 attempts to define the sequence of human chromosome 2 according to “UCSC Genome Browser hg 19 human genome assembly.” However, the UCSC genome browser is not a static sequence, but is updated and modified over time. Thus, the claim is indefinite because there are different versions of the genome assembly and a skilled artisan would not know which version the instant claims were encompassing.
It is noted that the method comprises the use of guide sequences of SEQ ID NOs. 1-94, which necessarily direct wherein the genetic modifications of claims 48 and 56 occur.
Claim 52 recites the limitation "the viral vector" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 52 is dependent upon claim 48, but is likely supposed to be dependent upon claim 51. However, claim 51 recites, “the vector is a virus.” Thus, simply amending claim 52 to be dependent upon claim 51 will not suffice in overcoming the rejection.
Applicant should consider amending claim 52 to recite, “The method of claim [[48]]51, wherein the virus
or
Applicant should consider amending claim 51 both 52:
In claim 51: “wherein the vector is a viral vector virus.”
In claim 52, “The method of claim [[48]] 51, wherein the viral vector is a lentiviral vector, a retroviral vector, an adenoviral vector or an adeno-associated viral vector
Claim 53 is defining the cells within the method of claim 48, and recites, “wherein the isolated cell is an embryonic stem cell a somatic stem cell, a progenitor cell, a bone marrow cell, a hematopoietic progenitor cell or hematopoietic stem cell.”
However, the method of claim 48 refers to a cell before genetic modification and a cell that has been genetically modified. Thus, it is not clear which cells claim 53 is referring back to. This is an antecedent basis rejection. A claim is indefinite when it contains words or phrases whose meaning is unclear. In re Packard, 751 F.3d 1307, 1314, 110 USPQ2d 1785, 1789 (Fed. Cir. 2014). The lack of clarity could arise where a claim refers to "said lever" or "the lever," where the claim contains no earlier recitation or limitation of a lever and where it would be unclear as to what element the limitation was making reference. Similarly, if two different levers are recited earlier in the claim, the recitation of "said lever" in the same or subsequent claim would be unclear where it is uncertain which of the two levers was intended. MPEP 2173.05(e).
Claim 54, dependent upon claim 48 recites, “the at least one genetic modification is a deletion, insertion or substitution of the nucleic acid sequence.” However, claim 48 recites the genetic modifications occur in “genomic DNA” and the only other recitation of “a nucleic acid sequence” refers to the guide sequences of SEQ ID NOs. 1-94. Thus, the claim lacks proper antecedent basis.
Claims 49-51, 55-60 are included in the rejection because they depend from a rejected claim.
Conclusion
No claims are allowed. The subject matter of claims 48-60, drawn to a method of genetically modifying a cell comprising the use of a vector comprising a PAM sequence, a tracrRNA, and guide sequences of SEQ ID NOs. 1-94, is free of the art. Further, the instant application is a divisional of parent patent US Patent No. 11,572,543, and the claims of the instant application are consonant with a non-elected invention from a restriction requirement therein. As such, no double patenting rejection is warranted. However, the claims are objected and rejected for the reasons stated above. Amendments which correct the issues raised above should advance the application to allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633