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 .
Claim Status
Claims 1, 5, 15-20, 22, 36-42, 98-99, 102-106 and new claims 107-108 are pending and examined here.
Priority
Although, the application claims the benefit of provisional application 63/237, 018, filed on 08/25/2021, it enjoys the benefit 08/24/2022 as it fails to fulfill the requirement to satisfy the 112(a). A claim is only entitled to the effective filing date of a benefit or priority document if that document provides the claim with an enabling disclosure and adequate written description. 35 U.S.C. 119(e)(1); 35 U.S.C. 120; MPEP 1893.03(c), part (III); MPEP 2139.01 (pre-AIA ); MPEP 2152.01. As such, if a claim is correctly rejected under 35 U.S.C. 112(a) for lack of enablement or lack of adequate written description, it necessarily cannot be entitled to the filing dates of its benefit or priority documents.
Thus the examined claims enjoy the filing date of instant application: 8/24/2022.
Response to Arguments
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive. Here, the amendments and the Remarks do not overcome the 112(a) rejection, thus the examined claims enjoy the filing date of 08/24/2022.
Claim Objections
Claim 36 is objected to because of the following informalities: there appears to be non-relevant text in the claim or incorrect symbol(s) of amino acids: “encodes RASAL3 p.Terl012Glyext*?” and last line of claim “p.Met1?” (emphasis added to point out language that needs correction; Ter is not a recognized amino acid symbol), or asterisks at various points in the claim (e.g. “RASAL3 p.Gln999*”); if the asterisk(s) has a relevance, it needs to be stated. Please examine for similar non-relevant texts in the claim. Appropriate correction is required.
Claim Interpretation
Claim 20 recites, in lines 8-19, “or the complement thereof” for the limitation of an mRNA molecule. The specification on pg. 6, lines 11-12: “One strand of a nucleic acid also refers to its complement.” Similar language is used as a limitation for a nucleic acid encoding a RASAL3 variant, see, e.g., cl. 15, line 3, cl. 16, line 3-4, and a genomic nucleic acid molecule, e.g., see cl. 20, line 5. Thus, the “complement” is understood to be just a strand and not its complementary strand.
Claim Rejections - 35 USC § 112
The rejection of 1, 5, 15-20, 22, 36-42, 98-99, 102-106 is maintained, while new claims 107-108 are rejected as noted below.
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 1, 5, 15-20, 22, 36-42, 98-99, 102-108 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. Briefly, the language that each species is fully complementary to the target molecule is insufficient, since even knowing a fully complementary sequence does not allow a skilled artisan to envision the “RASAL3 inhibitor” that inhibits the expression of target molecule with any reasonable expectation of success.
The written description rejection is applied for the claimed “RASAL3 inhibitor” of claim 1 and claim 36.
Claim 1 recites a method of inhibiting RAS protein Activator Like 3 (RASAL3) in a human subject having asthma, the method comprising administering a RASAL3 inhibitor to the subject, wherein the RASAL3 inhibitor comprises an antisense nucleic acid molecule, a siRNA, or a shRNA that is fully complementary to a RASAL3 nucleic acid molecule. Claim 36 recites wherein the RASAL inhibitor comprises an antisense nucleic acid molecule, a siRNA, or a shRNA that is fully complementary to a RASAL3 nucleic acid molecule, or the complement thereof, wherein the RASAL3 variant nucleic acid molecule, or the complement thereof, encodes claimed variants. Claims 103 and 104 recite an siRNA that is fully complementary to a RASAL3 nucleic acid molecule. Claims 107 and 108 recite the “RASAL2 inhibitor comprises an antisense nucleic acid molecule that is fully complementary to a RASAL3 nucleic acid molecule.”
The claimed invention of RASAL3 inhibitor encompasses any antisense nucleic acid molecule, any siRNA or any shRNA that is fully complementary to a RASAL3 nucleic acid molecule.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, there is not sufficient disclosure of representative number of RASAL3 inhibitor species of claimed RASAL3 ASN, siRNA, or shRNA that is fully complementary to a RASAL3 nucleic acid molecule. (gRNAs are not a species of siRNA, shRNA or antisense molecules.) The RASAL3 inhibitor genus encompasses a large number of variants and molecules that have the same activity as an antisense nucleic acid molecule (ASN), a siRNA or a shRNA that is fully complementary to RASAL3 nucleic acid, the RASAL3 inhibitor genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of RASAL3 inhibitor or functional equivalents thereof. Additionally, the specification does not describe the complete structure of a representative number of species of an ASN, a siRNA or a shRNA RASAL3 inhibitor of the large genus.
A prior art search shows that Saito et al. (2015, Eur. J. Immunol. 45, pg. 1512-1523, pg. 1515) disclose the use of lentiviral-encoding shRNAs (Fig. 2C-E) and disclose creating transgenic RASAL3-deficient mice. However, Saito et al. do not disclose the sequences of shRNA.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, no other identifying characteristic is indicated except a RASAL3 inhibitor. Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since, by Applicant’s definition of RASAL3 inhibitor or functional equivalent thereof, all members of the claimed genus will have that characteristic. Further, no identifying characteristics of the RASAL3 inhibitor are disclosed.
The inventions of claims 5, 15-20, 22, 98, 102-103, 105, 107 require the use of the inventions of Claim 1 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
The inventions of claims 37-42, 99, 104, 106, 108 require the use of the inventions of Claim 36 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In conclusion, due to Applicant’s lack of disclosure of a structure of a species of the claimed broad genus of RASAL3 inhibitor, the disclosure is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Response to Arguments
The Applicant's arguments filed 12/04/2025 (“the Remarks”) have been fully considered but they are not persuasive.
The Remarks argue that the claim amendments overcome the rejection. The amended language recites “antisense nucleic acid molecule, siRNA, and shRNA are fully complementary to a RASAL3 nucleic acid molecule” and since the nucleotide sequences of RASAL3 are known, “therefore the complete structures” of the claimed species is known (pg. 26).
The argument is not persuasive.
The antisense nucleic acid molecule, siRNA, shRNA are species of a limitation of “RASAL3 inhibitor” genus. Thus, the language that each species is fully complementary to the target molecule is insufficient, since even knowing a fully complementary sequence does not allow a skilled artisan to envision the “RASAL3 inhibitor” that inhibits the expression of target molecule with any reasonable expectation of success. The specification fails to provide a structure of a species of the claimed broad genus of the broad claimed genus RASAL3 inhibitor.
Thus, the rejection is maintained.
35 U.S.C. 112(a) enablement
The rejection of 1, 5, 15-20, 22, 36-42, 98-99, 102-104, 105-106 is maintained, while new claims 107-108 are rejected as noted below.
Claims 1, 5, 15-20, 22, 36-42, 98-99, 102-108 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are two independent claims and their dependents: claim 1 and its dependents, and claim 36 and its dependents. Claim 1 is directed to inhibiting RASAL3 in a human subject having asthma, the method comprising administering recited RASAL nucleic acid inhibitor. Claims 36-42, 99, 104, and 106 are directed to inhibiting RASAL3 in a human subject with asthma by administering a therapeutic agent that treats or inhibits asthma and the method further directed to determining the subject having a RASAL3 reference (does not have the RASAL3 variant nucleic acid molecule) or a recited variant genotype, and administering a varying dose of a therapeutic agent and an RASAL3 inhibitor to the subject based on the RASAL3 genotype of the subject.
When considering the scope of enablement, the Wands factors need to be reviewed, which poses whether the experimentation needed to practice the invention is undue or unreasonable. Determining undue experimentation requires analysis of, but not limited to: (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.
The breadth of the claims and nature of the invention: When read in the light of the specification (“present disclosure provides methods of treating a subject having an inflammatory disease,” pg. 2, lines 12-13), the nature of the invention, as directed by claim 1, is to treat any human subject with asthma by administering a RASAL3 inhibitor, wherein the RASAL3 inhibitor comprises an ASN, a siRNA, or a shRNA that is fully complementary to a RASAL3 nucleic acid molecule regardless of the genotype of the subject. Further to be a RASAL3 inhibitor, the claimed fully complementary RASAL3 inhibitor need to hybridize to the RASAL3 transcript (e.g., pg. 10, lines 1-10); thus deletion of “hybridizes” does not alter the reasoning of the prior or this enablement rejection. Claim 1 is broad in scope in that administering any ASN, any siRNA or shRNA that is fully complementary to a RASAL3 nucleic acid molecule will treat any human subject with asthma, regardless of the genotype of the subject. Claim 36 directs to a method of treating a human subject with asthma by, first, determining whether subject carries a RASAL3 reference (subject does not have the RASAL3 variant nucleic acid molecule) or heterozygous genotype sequence (any of the claimed variants) and, second, administering varying dose of a therapeutic agent and RASAL3 inhibitor depending on RASAL3 genotype, wherein the RASAL3 inhibitor comprises an ASN, a siRNA, or a shRNA that is fully complementary (i.e. hybridizes) to a RASAL3 nucleic acid molecule.
The state of the prior art:
RASAL3 and Asthma: A prior art search provides a few studies elucidating the function of RASAL3. A consistent observation is RASAL3’s role in T-cells. However, there are no studies suggesting association between administering RASAL3 inhibitor to treat asthma. Saito et al. (2015, Eur. J. Immunol., 45, 1512-1523) highlight identifying “a novel Ras GTPase-activating proteins protein RASAL3, which is predominantly expressed in cells of hematopoietic linages, including NKT, B, and T cells” (Abstract) Saito et al. generated a systemic RASAL3-deficient mouse that exhibited a severe decrease in NKT cells in the liver at 8 weeks of age and suggest that there is a “dysregulated Ras signaling in the NKT cells,” leading to a conclusion that RASAL3 plays an important role in the expansion and functions of NKT cells in the liver by negatively regulating Ras/Erk signaling, and might be a therapeutic target for NKT-associated diseases (Abstract). A putative post-filing study of RASAL3 deficient mice by Saito et al. (2021, Frontiers in Immunology, 12, pg. 1-11) discloses that RASAL3-deficiency results in an enhanced inflammatory response in neutrophils (pg. 6) and that “mice lacking RASAL3 (RASAL3-KO) demonstrate accelerated mortality in septic shock model via induction of severe organ damage and hyperinflammatory response” (abstract), leading the authors to suggest the use of RASAL3 agonists as a novel therapeutic for neutrophil-driven inflammatory conditions (pg. 10). Thus, Saito’s et al. studies suggest that the loss of RASAL3, at least in neutrophils, results in increased inflammatory response, while an agonist of RASAL3 would be a therapeutic agent to decrease the inflammatory response. Meanwhile the instant claims encompass administering recited RASAL3 inhibitor to subjects with asthma, a disease characterized by hyper-reactivity inflammatory reaction (par. 3, instant specification). Thus claimed subject matter is opposite of the suggestion of Saito et al., i.e. to treat with RASAL3 agonists to decrease inflammatory reaction in neutrophils. Thus, leading one of skill in the art to conclude that further studies are required to understand the role of RASAL3 in asthma; including to elucidate the association of variant molecule of RASAL3 encoding pLof and asthma.
Nucleic Acid inhibitors: The claims encompass treatment with an RASAL3 inhibitor comprising antisense nucleic acid molecule (ASN), siRNA, shRNA that is fully complementary (i.e. hybridizes, see pg. 10, lines 1-10) to a RASAL3 transcript. Usually, prior to human administration, there are series of steps/studies that need to be taken before a siRNA/shRNA/ASN drug can be administered to a human subject. Paton (2017, Drugs of the Future, 42, 335-343) discloses steps taken to identify a therapeutic siRNA: 1) identify siRNA(s) that specifically hybridizes with the target gene, ideally in multiple species, including human; 2) conduct bioinformatic analysis to design ~100 siRNAs for cross species hybridization/activity (pg. 337); 3) conduct in vitro studies to identify a handful of siRNAs with ideal inhibition (i.e. ED50) values (pg. 337); 4) identify optimal modifications for in vivo stability (Tables I and II); 5) conduct in vivo studies in model organisms (usually includes mice and monkeys) to demonstrate inhibition of target gene using modified siRNA that is sufficiently stable and is protected from in vivo degradation (pg. 337); 6) identify a delivery vehicle to improve delivery of siRNAs and maximize potency, which either includes further modification of the siRNA or identify a vehicle to deliver the siRNA to target organ/tissue (pg. 337-338); 7) undergo clinical studies to identify modified siRNAs in delivery vehicle that has acceptable side-effects with optimal outcome (pg. 338-339).
The level of predictability in the art: The level of predictability in the art is low. MPЕР 2164.03, provides that when there is a lack of guidance in the prior art, the application needs more detail as to how to make and use the invention in order to be enabling. However, the specification fails to provide sufficient guidance.
Inhibitory nucleic acid molecule: The specification provides that the range of isolated nucleic acid that hybridizes to the target RASAL3 nucleic acid is from 5 to about 5000 nucleic acid (par. 112-113). Thus, considering just the canonical siRNA of 21 nt. for a target of RASAL3 nucleic acid molecule (SEQ ID NO: 1 is 12,921 nt.) there are a possibility of 12,900 siRNAs, not considering that there are various forms of siRNAs (e.g. to note a few, there are canonical siRNAs, asymmetric siRNAs, segmented siRNAs). One of skill in the art recognizes that not all siRNAs are equally efficient, and some siRNAs that are fully complementary do not inhibit at all, and that various factors are involved in designing efficient siRNA and their efficiency is also influenced by the secondary structure of the target sequence (2008, Gredell et al, Biotechnology and Bioengineering, 100, pg. 744-755). Thus, just picking any site on the RASAL3 transcript molecule is insufficient, since additional factors need to be considered. None of the additional factors, except for the size of the very broad range of inhibitory nucleic acid molecule and that the claimed RASAL3 inhibitor is fully complementary to the target transcript. Thus, there is uncertainty regarding which sequence of claimed RASAL3 inhibitor will inhibit the target transcript and would require undue experimentation.
Asthma: Similarly, focusing on just asthma, Aun et al. (2017, J. of Asthma and Allergy, 10, 293-301) highlight that “[d]ifferent phenotypes have been described in asthma but there is no standard way to distinguish them. They differ regarding clinical parameters, physiological criteria and environmental triggers, and biomarkers to identify distinct endotypes are needed. Animal models are limited for not being able to mimic all features and phenotypes of human asthma” (pg. 294). Thus, Aun et al. provide that there are inconsistent clinical parameters. Thus, even though, the specification associated childhood asthma with various different cohorts (UKB, GHS, and Sinai, see Fig. 1), due to difficulty in differing clinical parameters it is difficult to determine if each cohort has same clinical parameters/physiological criteria in defining childhood asthma. Here, the claimed invention indicates that reducing the expression of RASAL3 transcript will treat asthma, but the specification fails to demonstrate that reducing the expression of RASAL3 transcript will treat asthma and would require undue experimentation.
Genome wide association studies – A few suggestions provided by Plenge et al. (2013, Nature Reviews Drug Discovery, 12, 581-594) for gene-drug pair target validation are that it is critical 1) to have a robust finding that the causal variant is associated with medical trait of interest, especially for variants discovered by GWASs (pg. 590) and 2) a biological function of the causal gene and causal variant are known and suggest that “studies in human tissues are invaluable for understanding the effects of individual alleles” (pg. 590).
Although genome/exome sequence studies are gaining in prominence due to reduced costs, there are still issues concerning the causal link that is suggested between the genetic variation and a disease phenotype. Burgess et al. (2018, Ann. Rev. of Genomics and Human Genetics, 19, 303-327) disclose that an observational correlation between a suspected risk factor and an outcome does not necessarily imply that interventions on levels of risk factor will have a causal impact on the outcome (correlation is not causation) (Abstract). It could be an issue of confounders, common determinants of the risk factor and the outcome, that give rise to the association (pg. 305). Here, the specification does not provide a physiological study demonstrating to provide support for the correlation, i.e. that a) asthma patients overexpress RASAL3 protein, or b) decreasing the expression of RASAL3 will treat asthma regardless of the genotype of the subject with asthma. The claimed invention would require undue experimentation.
The amount of direction provided by the inventor/existence of working examples: The specification provides that “no variants of the RASAL3 gene or protein have any known association with an inflammatory disease” (par. 23) and adds that the specification provides “surprisingly” a variant of RASAL3 gene associated with a decreased risk of developing an inflammatory disease and that variant of “RASAL3 itself is responsible for a protective effect in an inflammatory disease.” The association studies include childhood asthma. The specification provides a data correlation between a RASAL3 variant and a decreased risk of childhood asthma: “Table 3 shows association of RASAL3 pLOF variant Ala414fs (r5751462297) with inflammatory diseases” (par. 206). Here, the specification provides a promising hypothesis, that of an association of a variant (Ala414fs) and a risk of inflammatory disease, or allergic diseases (par. 206).
However, the specification does not disclose a therapeutic recited RASAL3 inhibitor and its corresponding in vitro and/or in vivo studies, required for one of skill in the art to practice the claimed invention. The specification does not provide any studies demonstrating administration of recited RASAL3 inhibitor that treats asthma/inflammatory disease in an animal model with a reference RASAL3 gene, alone or co-administered with a therapeutic agent. Further, the specification also lacks specificity regarding which organ it will target to treat asthma, a skilled artisan would assume the lungs, but the specification notes that RASAL3 expression levels in various tissues (blood cells, small intestine and lungs was the highest, pg. 113) thus it is not certain which tissue type is targeted. Claim 1 recites treatment of a subject with asthma with claimed RASAL3 inhibitor; the fact that a gene mutation resulting in variant polypeptide expression (if it is expressed) is associated with a positive phenotype in a subject does not necessarily mean that decreasing the wild-type’s expression could be effectively used as a therapeutic treatment. Claim 36 also indicate “a RASAL3 variant nucleic acid molecule,” (lines 5, 9) which encompasses any variant listed in the claim. The specification does not include any studies whether any of these variants, first, actually is a loss-of-function variant, and, second, provide a decreased risk of developing asthma, i.e. the specification does not provide sufficient confirming evidence providing a causal connection between a variant of RASAL3 gene and a lower risk of asthma. The loss-of-function studies, i.e. functional analysis of at least of one of the claimed variant would be helpful in removing uncertainty. Nor does the specification disclose how one of skill in the art would distinguish between the beneficial effects of the recited RASAL3 inhibitor and a therapeutic agent that treats asthma or distinguish between the effects of administration of recited RASAL3 inhibitor and a therapeutic agent; as recited in claim 36 and claim 16, both of which require co-administration of RASAL3 inhibitor and a therapeutic agent that treats asthma in a human subject, who either is a heterozygous or a RASAL3 reference (i.e. a subject carrying a non-variant RASAL3). These studies would be helpful in removing uncertainty for a skilled artisan before administering claimed inhibitor to a human subject to treat asthma.
The quantity of experimentation: Thus, based on the above on the review of all the Wands factor criteria, there would be a need of undue experimentation for one of skill in the art to practice the method of treating a subject expressing RASAL3 reference having asthma, the method comprising administering a RASAL3 inhibitor to a subject, wherein the RASAL3 inhibitor comprises an antisense nucleic acid molecule (ASN), a siRNA, or a shRNA that hybridizes to a RASAL3 nucleic acid molecule that is not a RASAL3 variant nucleic acid molecule.
Here the specification does not provide a) a therapeutic inhibitory nucleic acid molecule that inhibits RASAL3 expression in vivo and that treats asthma in a human subject or in vitro studies to alleviate the uncertainty, b) if predicted loss of function (pLoF) is an actual a loss-of-function mutation, c) any functional studies demonstrating a causal link between the genetic variants and their protective nature, i.e. lower risk of developing asthma, either in vivo or in vitro.
Response to Arguments
Applicant's arguments filed 12/04/2025 (“the Remarks”) have been fully considered but they are not persuasive.
The Remarks allege that the amended claims overcome Office’s mistaken conclusion that the specification is lacking enabling disclosure (identification of a therapeutic inhibitory nucleic acid molecule that inhibits RASAL3 expression and that treats asthma in a human subject; demonstration of predicted loss of function is an actual loss of function; a demonstration of causal link between claimed RASAL3 variant of cl. 36 and protective nature, besides a correlation). The amended claimed RASAL3 inhibitor are designed to be inhibitory since the language recites that the inhibitor species is “fully complementary to a RASAL3 nucleic acid”, and because “the recited inhibitor of RASAL3 does not turn on whether any particular RASAL3 variant nucleic acid molecule is present in the cell at issue” and there is no requirement that the link be causal. The Remarks add:
“the art of administering an inhibitory nucleic acid molecule to a subject was sufficiently advanced as of Applicant's earliest claimed filing date that there would have been no requirement for undue experimentation to inhibit RASAL3 in a cell in a human subject (compare, the enclosed datasheet for "RASAL3 siRNA (m)" indicating that the product "is recommended for the inhibition of RASAL3 expression in mouse cells") (emphasis added)).
The argument is not persuasive.
The amended claims do not overcome the enablement rejection. Both the specification and the claimed invention require to be enabling. The statute require both “making and using it,” which here, neither is fulfilled. The claimed RASAL3 inhibitor is not made nor used to treat a patient with asthma. Examiner concedes that the art of designing siRNAs is known, but when there are possible of 12,900 siRNAs that can be designed, it is uncertain which one will inhibit the expression of target transcript. Pointing to a siRNA in a mouse does not overcome the lack of enablement rejection. A skilled artisan would need to make and then test various claimed RASAL3 inhibitors for to achieve effective inhibition in a human subject to treat asthma (which may require a clinical trial, in vitro animal model to test, etc. . .) and that is to practice the invention of claim 1. Thus, the requirement is undue. As noted in the rejection, the specification lacks sufficient enabling disclosure of a promising correlative observation. The fact that a gene mutation resulting in variant polypeptide expression (if it is expressed) is associated with a positive phenotype in a subject does not necessarily mean that decreasing the wild-type’s expression could be effectively used as a therapeutic treatment is uncertain.
35 U.S.C. 112(b):
Although the Remarks of 12/04/2025 fail to address the 112(b) rejection, rejection of claims 1 and 36 and their dependents under 112(b) is withdrawn. For cl. 1, the language of “RASAL3 that is not a RASAL3 variant” is deleted, while for claim 36 the variants are listed and the language of “predicted-loss of function” is deleted.
Conclusion
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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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600