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 response filed 05/01/2026 has been received and considered entered. This is a response to amendments and arguments filed 05/01/2026.
Election/Restrictions
Claim 42 stands withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/16/2025.
Claims Status
Claims 3-4, 6, 9-12, 14-18, 20-21, 25-26, 28-30, 32-33, 36, 38-39, 41, 43, 46, 49-50, 54, 56-57, 61-64, 66-67, 70, 72-73, 75, 78-79, 81, 83-84, 86 is/are cancelled. Claims 1-2, 5, 7-8, 13, 19, 22-24, 27, 31, 34-35, 37, 40, 42, 44-45, 47-48, 51-53, 55, 58-60, 65, 68-69, 71, 74, 76-77, 80, 82, 85, 87 is/are currently pending with claims 42 withdrawn. Claims 1-2, 5, 7-8, 13, 19, 22-24, 27, 31, 34-35, 37, 40, 44-45, 47-48, 51-53, 55, 58-60, 65, 68-69, 71, 74, 76-77, 80, 82, 85, 87 is/are under examination.
Claim Objections
Claim 2 is objected to because of the following informalities: there is a missing period [.] at the end of the claim. Appropriate correction is required.
Claim 55 is objected to because of the following informalities: “is” in line 3 should be “are”, as the subjects of the verb are the first and second regulatory elements. Appropriate correction is required.
Claim Interpretation
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
Claims 31 and 34 only recite further limitations regarding the adenosine deaminase domain recited as optional in claim 27. As claims 31 and 34 are only drawn to further limitations of an optional limitation of claim 27, all limitations of claims 31 and 34 are considered to be optional.
Claim 51 only recites further limitations regarding “the first Cas protein” and “the second Cas protein” of claim 48, which are limitations only recited in an optional limitation in lines 6-7 of claim 48. As claim 51 is only drawn to further limitations of optional limitations of claim 48, all limitations of claim 51 are considered to be optional.
Claim 44 recites an intended use of the claimed product “A system…comprising…a Cas protein of claim 1; one or more detection aptamers…and an oligonucleotide-based masking construct comprising a non-target sequence”. According to MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. The intended use recited in claim 44 does not appear to impart any structure to the claimed product. Therefore for the purpose of examination, claim 44 is directed to “A system…comprising…a Cas protein of claim 1; one or more detection aptamers…and an oligonucleotide-based masking construct comprising a non-target sequence”.
Claim 47 recites an intended use of the claimed product “A system…comprising: a Cas protein of claim 1; at least one guide polynucleotide…and an oligonucleotide-based masking construct comprising a non-target sequence” (lines 1-7). According to MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. The intended use recited in claim 47 does not appear to impart any structure to the claimed product. Therefore for the purpose of examination, claim 47 is directed to “A system…comprising: a Cas protein of claim 1; at least one guide polynucleotide…and an oligonucleotide-based masking construct comprising a non-target sequence” (lines 1-7).
Claim 68 recites an intended use of the claimed product “The composition of claim 1”. According to MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. The intended use recited in claim 68 does not appear to impart any structure to the claimed product. Therefore for the purpose of examination, claim 68 is directed to the composition of claim 1.
Claim Rejections - 35 USC § 112
112(a):
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 27, 37, 44, 48, 51 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.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "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 (see i)(A) above), reduction to drawings (see i)(B) above), 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 i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claim 27 recites that the deaminase and the Cas protein are “covalently or non-covalently linked” (line 2). However, the disclosure only discloses covalent linkages. It is not apparent, based on the disclosure, what structures are encompassed by non-covalent linkages between two protein sequences. As such, the disclosure only provides sufficient written description for covalent linkages.
Claim 37 recites that “modification of the nucleotides in the target nucleic acid treats a disease caused by a G[Wingdings font/0xE0]A or C[Wingdings font/0xE0]T point mutation or a pathogenic SNP…or…caused by a T[Wingdings font/0xE0]C or A[Wingdings font/0xE0]G point mutation or a pathogenic SNP.” Claim 37 also recites that the disease optionally comprises “cancer, haemophilia, beta-thalassemia, Marfan syndrome, or Wiskott-Aldrich syndrome” (lines 3-4). The specification does not provide a description of methods by which the composition of claim 24 is administered to a patient in need or an animal model representative of any disease, wherein the composition is targeted to any therapeutically-relevant nucleotide sequence, and wherein administration of the composition and modification of the therapeutically-relevant nucleotide sequence results in treatment of a disease. While cancer, haemophilia, beta-thalassemia, Marfan syndrome, and Wiskott-Aldrich syndrome are listed as possible target disease, the disclosure does not teach any particular target sequence and modification of said target sequence which would treat any of these disease, not does the disclosure provide evidence that the claimed composition is capable of treating any of these diseases. An artisan would not be able to determine, based on the present disclosure, that the applicants were in possession of a composition which could treat any disease.
Claim 44 recites “detection aptamers, each designed to bind to one or more target polypeptides, each detection aptamer comprising a masked promoter binding site or masked primer binding site and a trigger sequence template” (lines 4-6). However, the disclosure has not provided a structure by which an aptamer can bind to a polypeptide. Paragraph [0027] teaches that the aptamer “comprises a polynucleotide-tethered inhibitor that sequesters an enzyme” in an embodiment. A search of the term “polynucleotide-tethered inhibitor” does not produce results, indicating that this is not a term commonly used in the art. It is unclear what structure is described by “a polynucleotide-tethered inhibitor”. An artisan would not be able to determine the structures required to fulfill the limitations of claim 44 regarding detection aptamers. Claim 45 depends on claim 44 but does not rectify this lack of written description.
Claims 48 and 51 require a Cas protein “linked to an inactive first portion of an enzyme or reporter moiety, wherein the enzyme or reporter moiety is reconstituted when contacted with a complementary portion of the enzyme or reporter moiety” (claim 48). However, the specification and drawings do not provide any structures fulfilling these requirements. It would not be clear to an artisan what enzymes or reporter moieties would fulfill these requirements, nor would it be clear to an artisan that the applicants were in possession of such enzymes or reporter moieties. As such, claims 48 and 51 lack sufficient written description.
Enablement:
Claims 24, 37, 68, 74, 87 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 methods of modifying target nucleic acids in vitro, and compositions for use in these methods, does not reasonably provide enablement for methods of treating any disease, or for compositions having the function of treating any disease. 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 or use the invention commensurate in scope with these claims. This rejection is maintained.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims:
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed methods of claims 74 and 87 is that they encompass methods of treating or preventing any disease in a subject of any species by administering the claimed composition. The broadest reasonable interpretation of the required function of the composition of claim 37, and of a function encompassed by the composition of claim 24, and of the intended use and only further limitation of the composition of claim 68, is that the composition be capable of “remedying” or treating any disease when administered. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The amount of direction provided by the inventor and the level of predictability in the art:
Claim 37 recites that the claimed composition can be used to remedy “a disease caused by a G[Wingdings font/0xE0]A or C[Wingdings font/0xE0]T point mutation or a pathogenic SNP…or…caused by a T[Wingdings font/0xE0]C or A[Wingdings font/0xE0]G point mutation or a pathogenic SNP”, wherein the disease can comprise “cancer, haemophilia, beta-thalassemia, Marfan syndrome, or Wiskott-Aldrich syndrome”. The specification does not provide a description of methods by which the composition of claim 1 is administered to a patient in need or an animal model representative of any disease, wherein the composition is targeted to any therapeutically-relevant nucleotide sequence, and wherein administration of the composition and modification of the therapeutically-relevant nucleotide sequence results in remediation of a disease. While cancer, haemophilia, beta-thalassemia, Marfan syndrome, and Wiskott-Aldrich syndrome are listed as possible target disease, the disclosure does not teach any particular target sequence and modification of said target sequence which would remedy any of these disease, not does the disclosure provide evidence that the claimed composition is capable of treating any of these diseases. The art at the time of filing taught that while Cas13 showed promise for therapeutic applications in vivo, delivery in vivo and side effects were unresolved challenges that must still be overcome in order to enable the use of CRISPR/Cas13 systems in therapeutic applications, and CRISPR/Cas13 knockdown of mRNA had not yet been shown (see Granados-Riveron, 2018, page 4109 and Table 1). The specification as filed does not provide guidance that overcomes this unpredictability within the art.
The existence of working examples:
What is enabled by the working examples is narrow in comparison to the breadth of the claims: The specification discloses only in vitro administration of the composition of claim 1, in mammalian cells (HEK293FT) and bacterial cells (E. coli) (see Figs. 22, 23; paragraphs [1294]-[1307]); the specification does not disclose any working examples comprising in vivo administration of the claimed compositions.
The quantity of experimentation needed to make or use the invention:
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given that the nature of the invention is treatment or prevention of any disease in any subject, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials, or in animal models that are predictive of treatment in a representative number of diseases, in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully treating any CNS disorder or neurodegenerative disease. Therefore, Claims 24, 37, 68, and 87 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
Response to Arguments
Applicant's arguments filed 05/01/2026 have been fully considered but they are not persuasive.
Written Description:
The rejection of claims 27, 48, 51 were not addressed by arguments or amendments. The rejection of claim 36 was insufficiently addressed by amendment; the amendment of references to “remedying” of a disease with “treating” a disease does not alter the meaning of the rejected claim language such that the claim has sufficient written description.
Regarding claim 44, Applicant argues that aptamer “is a common term of art, and one skilled in the art would readily know the structure of the claimed aptamer capable of binding to a polypeptide” (page 17). The art teaches that there are methods of using selection pressure to drive evolution of aptamers which can bind to specific polypeptides, and in silico methods of designing aptamers which require significant experimentation (see Buglak, 2020), but this merely teaches experimental methods which may result in an aptamer capable of binding a particular polypeptide, not a method for reliably predicting the precise structure of such an aptamer. Claim 45 was inadvertently missed in the original written description rejection presented in the non-final rejection of claims; however, the subject matter of claim 45 was and is encompassed by the written description rejection of claim 44, as claim 45 was and is dependent of claim 44 and does not rectify the insufficient written description of claim 44.
Scope of Enablement:
Regarding claim 24, Applicant argues that “Claim 24 does not recite administration to a subject, in vivo use, or treatment of a disease”. However, claim 37 recites that the composition is capable of treating disease, and claim 37 depends on claim 24 and is thus broadly encompassed by claim 24. As such, treatment of a disease is encompassed by claim 24, but is not the entire scope of claim 24. Likewise, claim 74 is not limited to in vitro methods and encompasses methods of treating disease.
Claims 37, 68, and 87 are drawn to methods of treating disease. Applicant argues that “The Specification discloses treatment of each of these disease categories. As known in the art and recited in the Specification, mRNA targeting has been demonstrated to treat diseases” (page 19). Applicant does not indicate any particular teaching from the specification or the art which demonstrates this. A review of the specification does not yield evidence that any disease could be predicted to be treated by the claimed methods. Furthermore, evidence that one disease may be treated by targeting a specific mRNA in one particular method does not provide enablement for treatment of any other disease, or treatment of the same disease with a different target mRNA or different methodology. The rejection of claims for lack of enablement over the entire scope of the claims is maintained.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheng (US20190002875A1). This new rejection is necessitated by amendment.
Regarding claim 5, Cheng teaches an engineered CRISPR-Cas system comprising: a Cas protein of SEQ ID NO:12 (SEQ ID NO:12 is 100% identical to instant SEQ ID NO:4000, see below); a guide sequence capable of complexing with the Cas protein and directing binding of the complex to a target sequence; wherein the Cas protein comprises a nuclear localization signal and is fused to a base-editing domain, an RNA methyltransferase, an RNA demethylase, a splicing modifier, or a translation modification factor (claims 1, 3, 11-13).
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Allowable Subject Matter
Claims 1, 7-8, 13, 19, 22-23, 31, 34-35, 40, 47, 52-53, 58-60, 65, 69, 71, 76-77, 80, 82, 85 are allowed.
The following is a statement of reasons for the indication of allowable subject matter: a search of the art for SEQ ID NOs: 4102, 4150, 4200, 4250, 4298, 4300, 4400, 4500, 4600, 4700, and 5260 did not yield any results. These eleven sequences are considered representative of the 1,110 sequences recited in claim 1 for searching purposes.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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