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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 103-120, in the reply filed on 11-21-25 is acknowledged.
Claims 121-122 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11-21-25.
Claim Objections
There is no need to list the amino acid sequence literally AND refer to the SEQ ID NO in claim 103. Simply referring to the SEQ ID NO will do.
The term “animal” in the phrase “rodent animal” in claim 103 is redundant. Just say rodent.
ADAR1 in claim 103 should be spelled out before being abbreviated. ADAR1 refers to “adenosine deaminase acting on RNA 1” (pg 69, par 99) (see Wikipedia definition of “adenosine deaminase acting on RNA” 1, 2026). ADAR1 is distinguished from “adenosine deaminase 1” (ADA1) (see Wikipedia definition of “adenosine deaminase 1”, 2026).
While claim 103 says the rodent is “engineered”, it does not say the rodent is genetically modified. Claim 103 encompasses a rodent injected with an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but this is not what the invention appears to be. Claim 103 also encompasses a rodent injected with a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but (again) this is not what the invention appears to be. Claim 103 also encompasses a rodent in which one cell comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but (again) this is not what the invention appears to be. Claim 103 can be more simply and accurately written as ---A genetically modified rodent whose genome comprises a nucleic acid sequence encoding an [adenosine deaminase acting on RNA 1?] (ADAR1) comprising the amino acid sequence of SEQ ID NO: 16---.
Claim 105 requires “expression of the ADAR1 polypeptide”, but claim 103 encompasses injecting the rodent with an ADAR1 having the amino acid sequence of SEQ ID NO: 16; it never requires that the rodent comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 or that the nucleic acid sequence is expressed in the rodent. Therefore, claim 105 does not make sense.
Claims 113 and 114 require the rodent of claim 103 is heterozygous or homozygous, but there is nothing in claim 103 that requires the rodent is genetically modified or comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. Therefore, claims 113 and 114 do not make sense.
Claims 115 and 118 are objected to for reasons set forth regarding claim 103.
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.
Written Description
Claims 103-120 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.
The specification lacks written description for any rodent engineered to comprise an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 as required in claim 103 other than a genetically modified mouse whose genome comprises a replacement of an endogenous nucleic acid sequence encoding ADAR1 with an exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16.
Claim 103 is drawn to a rodent engineered to comprise an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. While claim 103 says the rodent is “engineered”, it does not say the rodent is genetically modified. Claim 103 encompasses a rodent injected with an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but this is not what the invention appears to be. Claim 103 also encompasses a rodent injected with a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but (again) this is not what the invention appears to be. Claim 103 also encompasses a rodent in which one cell comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, but (again) this is not what the invention appears to be.
Mali (WO 2020051555) injected a nucleic acid sequence encoding ADAR1 into mice (pg 103, para 366).
Tsuruoka (J. Biol. Chem., 2013, Vol. 288, No. 2, pg 826-836) taught a transgenic mouse whose genome comprises an exogenous nucleic acid sequence encoding ADAR1 (pg 827, “Mice”).
Example 1 (pg 226) describes making a targeting vector for making a genetically modified mouse whose genome comprises a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. SEQ ID NO: 16 encodes isoform p110 (pg 226, para 426).
Example 2 (pg 227-229) is prophetic and discusses making a transgenic mouse zygote comprising the targeting vector. However, the specification does not teach obtaining the mice, the embryos, or any rodent cells comprising the exogenous sequence as claimed.
The specification does not teach whether the exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 is under the control of the endogenous ROSA26 promoter or an exogenous ADAR1 promoter (although it appears not because SEQ ID NO: 16 is mRNA). The specification does not teach the exogenous sequence is under the control of a constitutive promoter as required in claim 105, a “tissue specific” promoter as required in claim 106, or an “inducible” promoter as required in claim 108.
The specification does not teach the phenotype of the mouse or how to use the mouse.
The specification does not teach obtaining any heterozygous or homozygous mice as required in claim 113 or 114.
The specification does not correlate the mice to any species of rodent, e.g. rat, beaver, squirrel, groundhog, muskrat, hamster, capybara, chinchilla, porcupine, gerbil, et al.
The specification does not teach obtaining cell, specifically hepatocytes or stem cells, comprising the exogenous sequence as required in claim 111, 118, 119, 120. The specification does not teach how to use hepatocytes or stem cells comprising the exogenous sequence as required in claim 111, 119, 120 other than a fertilized mouse egg or mouse ES cell for making the transgenic mouse.
Accordingly, the claims lack written description.
Enablement
Claims 103-120 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 a genetically modified mouse whose genome comprises an exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16, does not reasonably provide enablement for any rodent engineered to comprise an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. 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/use the invention commensurate in scope with these claims.
The specification does not enable making/using any rodent engineered to comprise an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 as required in claim 103 other than a genetically modified mouse whose genome comprises an exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16.
Claim 103 and its breadth are cited above.
Mali (WO 2020051555) injected a nucleic acid sequence encoding ADAR1 into mice (pg 103, para 366).
Tsuruoka (J. Biol. Chem., 2013, Vol. 288, No. 2, pg 826-836) taught a transgenic mouse whose genome comprises an exogenous nucleic acid sequence encoding ADAR1 (pg 827, “Mice”).
Example 1 (pg 226) describes making a targeting vector for making a genetically modified mouse whose genome comprises a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. SEQ ID NO: 16 encodes isoform p110 (pg 226, para 426).
Example 2 (pg 227-229) is prophetic and discusses making a transgenic mouse zygote comprising the targeting vector. However, the specification does not teach obtaining the mice, the embryos, or any rodent cells comprising the exogenous sequence as claimed.
The specification does not teach whether the exogenous nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 is under the control of the endogenous ROSA26 promoter or an exogenous ADAR1 promoter (although it appears not because SEQ ID NO: 16 is mRNA). The specification does not teach the exogenous sequence is under the control of a constitutive promoter as required in claim 105, a “tissue specific” promoter as required in claim 106, or an “inducible” promoter as required in claim 108.
The specification does not teach the phenotype of the mouse or how to use the mouse.
The specification does not teach obtaining any heterozygous or homozygous mice as required in claim 113 or 114.
The specification does not correlate the mice to any species of rodent, e.g. rat, beaver, squirrel, groundhog, muskrat, hamster, capybara, chinchilla, porcupine, gerbil, et al.
The specification does not teach obtaining cell, specifically hepatocytes or stem cells, comprising the exogenous sequence as required in claim 111, 118, 119, 120. The specification does not teach how to use hepatocytes or stem cells comprising the exogenous sequence as required in claim 111, 119, 120 other than a fertilized mouse egg or mouse ES cell for making the transgenic mouse.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use the rodent of claim 103, the embryo of claim 115, or the cells of claim 118.
Indefiniteness
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 105, 106, 108, 113, 114 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 105, 106, 108 require “expression of the ADAR1 polypeptide”, but claim 103 encompasses injecting the rodent with an ADAR1 having the amino acid sequence of SEQ ID NO: 16; it never requires that the rodent comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16 or that the nucleic acid sequence is expressed in the rodent. Therefore, claims 105, 106, 108 are indefinite.
Claims 113 and 114 require the rodent of claim 103 is heterozygous or homozygous, but there is nothing in claim 103 that requires the rodent is genetically modified or comprises a nucleic acid sequence encoding an ADAR1 comprising the amino acid sequence of SEQ ID NO: 16. Therefore, claims 113 and 114 are indefinite.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
A) Claims 103, 105-114, 118, 119 are rejected under 35 U.S.C. 103 as being unpatentable over Mali (WO 2020051555) in view of Kim (PNAS, 1994, Vol. 91, pg 11457-11461), EU176459 (2007), EU176799 (2007), HSU10439 (1994), BC038227 (2002).
Mali injected a nucleic acid sequence encoding ADAR1 into mice (pg 103, para 366).
Mali did not teach the nucleic acid sequence encoded an ADAR1 having the amino acid sequence of SEQ ID NO: 16 as required in claim 103.
However, the amino acid sequence of SEQ ID NO: 16 was described by Kim
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and nucleic acid sequences encoding SEQ ID NO: 16 were described by EU176459 (2007), EU176799 (2007), HSU10439 (1994), BC038227 (2002):
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“Expression” is not required in claim 103, so further limiting expression to being “constitutive” in claim 105 does not make sense. Claim 105 has been included because it is indefinite.
“Expression” is not required in claim 103, so further limiting expression to being “tissue specific” in claim 106 does not make sense. Claim 106 has been included because it is indefinite.
Mali taught a mouse as required in claim 107.
“Expression” is not required in claim 103, so further limiting expression to being “inducible” in claim 108 does not make sense. Claim 108 has been included because it is indefinite.
Mali taught a mouse as required in claim 109.
Mali taught a mouse as required in claim 110.
Mali observed expression in the liver (pg 15; para 45; pg 17, para 59; pg 20, para 71; pg 20, para 76; pg 78, para 271; pg 82, para 295; pg 92, para 324; pg 95, para 327; pg 97, para 345; pg 104, para 367; pg 105, para 370) which are hepatocytes as required in claim 111.
Mali observed expression in the liver of mice as required in claim 112 as cited above.
Claims 113 and 114 have been included because they are indefinite. They fail to further limit claim 103 which is not limited to a genetically modified rodent or a rodent whose genome comprises an exogenous nucleic acid sequence encoding ADAR1, so the rodent cannot be heterozygous or homozygous for anything as required in claims 113 and 114.
Claim 118 has been included for reasons set forth above for claim 103.
Mali taught the cells were in a mouse as required in claim 119.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
B) Claims 103-120 are rejected under 35 U.S.C. 103 as being unpatentable over Tsuruoka (J. Biol. Chem., 2013, Vol. 288, No. 2, pg 826-836) in view of EU176459 (2007), EU176799 (2007), HSU10439 (1994), BC038227 (2002).
Tsuruoka taught a transgenic mouse whose genome comprises an exogenous nucleic acid sequence encoding ADAR1 (pg 827, “Mice”).
Tsuruoka did not teach the nucleic acid sequence encoded an ADAR1 having the amino acid sequence of SEQ ID NO: 16 as required in claim 103.
However, the amino acid sequence of SEQ ID NO: 16 was described by Kim
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and nucleic acid sequences encoding SEQ ID NO: 16 were described by EU176459 (2007), EU176799 (2007), HSU10439 (1994), BC038227 (2002):
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Tsuruoka taught the genome of the mice contained the exogenous nucleic acid (pg 827, “Mice”) as required in claim 104.
Tsuruoka used a Lck distal promoter (pg 827, “Mice”) which causes “tissue specific” expression in thymocytes and T-cells as required in claim 105.
Tsuruoka taught a mouse as required in claim 107.
“Expression” is not required in claim 103, so further limiting expression to being “inducible” in claim 108 does not make sense. Claim 108 has been included because it is indefinite.
Tsuruoka taught a mouse as required in claim 109.
Tsuruoka taught a mouse as required in claim 110.
The mice of Tsuruoka inherently MUST contain hepatocytes comprising the exogenous nucleic acid as encompassed by claim 111 because the entire genome of the mouse contained the transgene.
The mice of Tsuruoka inherently MUST contain mouse hepatocytes as required in claim 112.
Tsuruoka taught the mice were heterozygous and homozygous for the transgene as required in claims 113, 114.
Claim 115 has been included for reasons set forth above for claim 103 and because Tsuruoka obtained mouse embryos containing the transgene (pg 827, “Mice”).
Tsuruoka taught the genome of the mouse embryos contained the exogenous nucleic acid (pg 827, “Mice”) as required in claim 116.
Tsuruoka mouse embryos (pg 827, “Mice”) as required in claim 117.
Claim 118 has been included for reasons set forth above for claim 103.
Tsuruoka taught the cells were in a mouse as required in claim 119.
Tsuruoka taught putting the exogenous sequence in fertilized eggs (pg 827, “Mice”) which are stem cells as required in claim 120. Tsuruoka also isolated spleen cells from the mouse (pg 827, col. 2, “Isolation of T-cells and B-cells”) which contain stem cells as required in claim 120.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638