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 .
DETAILED ACTION
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 1-3, in the reply filed on Jul. 27, 2026 is acknowledged.
Claims 1-11 remain pending in the current application, claims 4-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The requirement for the restriction of Inventions 1-V is still deemed proper and is therefore made FINAL.
Claims 1-3 have been considered on the merits.
Status of the Claims
Claims 1-11 are currently pending.
Claims 4-11 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Inventions, there being no allowable generic or linking claim.
Claims 1-3 have been considered on the merits.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks and containing an embedded hyperlink in 0051.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01.
Note to Applicant
Claims 9-11 are considered “use claims”. The claims provide an use for the targeting vector, the porcine fibroblast cell line, and the method of constructing a dual pig model of severe immunodeficiency and liver injury, respectively. However, since the claims do not set forth any steps involved in the method/process of using targeting vector, the porcine fibroblast cell line, and the method of constructing a dual pig model of severe immunodeficiency and liver injury, it is unclear what method/process applicant is intending to encompass. If these claims were to be rejoined they would be considered indefinite and would be rejected under 35 U.S.C. §112. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. In addition, the claims would be rejected under 35 U.S.C. §101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. §101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claims which appear to be composition claims lack the components or structures of the compositions. They do not fit into the statutory definition of “composition of matter” because the claims do not properly define a physical substance, but merely state a RAG2/IL2Rγ/FAH triple-gene targeting vector and a RAG2/IL2Rγ/FAH triple-gene knockout porcine fibroblast cell line. None of the claims contain structural elements, therefore the claims are directed to an abstract concept and not to an actual physical composition. In other words, the claims do not set forth any structure or components to the compositions, resulting in an improper definition of a composition, i.e., results in a claim which is not a proper composition claim under 35 U.S.C. §101.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3 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 rendered indefinite for not setting forth any structure for the RAG2/IL2Rγ/FAH triple-gene targeting vector. The claim contains one “wherein clause” describing particular aspects of the targeting vector, but the claim does not actually contain any physical structures or components that compose the targeting vector.
Additionally, the wherein clause lacks an antecedent basis for the structures or components being described. For instance, the terms “targeting vector” and “sgRNA” lack sufficient antecedent basis, since they are not positively recited to be part of the RAG2/IL2Rγ/FAH triple-gene targeting vector.
For the purposes of compact prosecution, the claim 1 will be interpreted as follows:
A RAG2/IL2Rγ/FAH triple-gene targeting vector, comprising a targeting vector that is an sgRNA expression vector based on a CRISPR/Cas9 system, and an sgRNA comprising a RAG2-sgRNA, an IL2Rγ-sgRNA, and an FAH-sgRNA;
wherein the sgRNA acts on a site located in a coding region of a pig RAG2 gene, a 5th exon of an IL2Rγ gene, and a 2nd exon of an FAH gene; and
wherein the nucleotide sequence of the RAG2-sgRNA is
Similarly, Claim 2 is rendered indefinite for not setting forth any structure for the RAG2/IL2Rγ/FAH triple-gene targeting vector. The claim contains one “wherein clause” describing particular aspects of the targeting vector, but the claim does not actually contain any physical structures or components that compose the targeting vector.
Additionally, the wherein clause lacks an antecedent basis for the structures or components being described. For instance, the term “a framework vector” lacks sufficient antecedent basis, since the term is not positively recited to be part of the RAG2/IL2Rγ/FAH triple-gene targeting vector.
Furthermore, the phrase " the term “a framework vector” lacks sufficient antecedent basis and renders the claim indefinite, since claim 1 does not contain a framework vector.
For the purposes of compact prosecution, the claim 1 will be interpreted as follows:
The RAG2/IL2Rγ/FAH triple-gene targeting vector according to claim 1, wherein sgRNA expression vector is apGL3-U6-sgRNA,
Claim 3 is rendered indefinite for not setting forth any structure for the RAG2/IL2Rγ/FAH triple-gene knockout porcine fibroblast cell line. The claim contains one “wherein clause” describing particular aspects of the porcine fibroblast cell line, but the claim does not actually contain any physical structures or components that compose the porcine fibroblast cell line. Additionally, the wherein clause lacks an antecedent basis for the structures or components being described. For instance, the term “porcine fetal fibroblast cell line” lacks sufficient antecedent basis, since it is not positively recited to be part of the RAG2/IL2Rγ/FAH triple-gene knockout porcine fibroblast cell line. Furthermore the wherein clause appears to contain a step and the claim is directed to a composition and not a method of producing the porcine fibroblast cell line.
Furthermore, the term “the porcine fetal fibroblast cell line” lacks sufficient antecedent basis and renders the claim indefinite.
For the purposes of compact prosecution, the claim 3 will be interpreted as follows:
A RAG2/IL2Rγ/FAH triple-gene knockout porcine fibroblast cell line, comprising a porcine fetal fibroblast cell line,
wherein the porcine fetal fibroblast cell line is produced by a method that comprises transfecting the RAG2/IL2Rγ/FAH triple-gene targeting vector according to claim 1a porcine fetal fibroblast cell line to obtain a targeted positive cell clone, and
wherein the porcine fetal fibroblast cell line is a -/-IL2Rγ-/YIFAH-/- triple-gene edited porcine fibroblast cell line.
Therefore, the metes and bounds of the claims are rendered vague and indefinite. The lack of clarity renders the claims very confusing and ambiguous since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
Appropriate correction is required.
Conclusion
No claims are allowed.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Fahrenkrug et al. (US 2016/0029604 A1)
Fahrenkrug teaches multiplex gene editing of swine RAG2 and IL2Rγ (0008 and 0080). In addition, Fahrenkrug teaches various disease modeling targets including FAH (0057). Fahrenkrug teaches that the multiplex gene edits can be made in one or more genes including IL2Rγ, RAG2 and FAH (claim 12) and it can be made in pigs (claims 1 and 10. Fahrenkrug teaches gene specific gRNA are cloned into the Church lab gRNA vector and where a Cs9 nuclease is provided by cotransfection of the hCas9 plasmid or mRNA synthesized from RCIScript-hCas9 (based on a CRISPR/Cas9 system) (0142). Fahrenkrug teach swine fibroblast cells containing a triple knockout for three genes (0143). Fahrenkrug does not teach the specific sgRNA sequences claimed for IL2Rγ, RAG2 and FAH as recited in claim 1, therefore the cells taught by Fahrenkrug would not contain the same gene edits.
Lei et al. "Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency." Scientific Reports 6.1 (2016): 25222.
Lei teaches CRISPR sequences designed to target Exon 1 of RAG2 and Exon 2 of IL2Rγ (pg. 2 para. 5). Lei teaches injecting the CRISPR/Cas9 RNA into pig zygotes (pg. 2 para. 5-6). Lei does not teach the same sgRNA sequences claimed for IL2Rγ, RAG2 and does not teach a sgRNA for FAH.
Li et al. "Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology." Scientific Reports 4.1 (2014): 5290.
Li teaches a targeting vector which is a sgRNA expression vector based on CRISPR/Cas9 (abstract and pg. 2 Col. 2 para. 1). Li teaches the targeting vector contains a gRNA targeting the exon 5 splice donor sequence and coding region of the Fah gene which introduces a null mutation in NRG embryos (pg. 2 Col. 2 para. 1-2). Li does not teach a targeting vector with three different sgRNAs targeting RAG2, IL2Rγ, and FAH.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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 on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
Prosecution Insights