Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
1. Claims 1, 2, 4, 5, 7, 9, 10, 14 – 17, and 31 – 36 are pending. Claims 1, 2, 4, 5, 7, 9, 10, and 31 – 36 are under consideration.
Withdrawn Claim Objections
2. The objection to claim 2 is withdrawn in view of Applicant’s amendment to the claim .
Withdrawn Claim Rejections
3. The rejection of claims 12 and 13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is rendered moot in view of Applicant’s cancellation of these claims.
4. The rejection of claims 1, 2, 4, 5, 7, 9, and 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to these claims.
Maintained Claim Rejections including new claims 35 and 36
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.
5. Claims 1, 2, 4, 5, 7, 9, 10, and 31 – 34 remain rejected and new claims 35 – 36 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. Although maintained, the rejection is revised in view of Applicant’s amendment to claim 1 and new claims 35 – 36.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make and use the invention based on the content of the disclosure is "undue".
Nature of Invention: The invention relates to methods of treating a subject having an autoimmune disorder, the methods comprising decreasing, in one or more cells in the subject, the amount of one or more genetic variants associated with susceptibility to the autoimmune disorder; and/or increasing, in one or more cells in the subject, the amount of one or more genetic variants protective against the autoimmune disorder (Applicant’s specification at page 1, para. 0004).
Breadth of the Claims: Regarding the method of claim 1 and dependents, the method is for treating a subject having any autoimmune disorder wherein the autoimmune disorder is an inflammatory disease treatable by increasing expression of one or more IL23 protective protein variants in the subject, the method comprising increasing in the subject an expression of one or more IL23R protein variants protective against the autoimmune disorder ("protective protein variant(s)"), the protective protein variant comprising one or more of a R381Q mutation, a G149R mutation, and a V362I mutation as compared to a corresponding wild type IL23R protein, wherein the increasing the expression of the one or more protective protein variants comprises altering immune cells and/or hematopoietic stem cells in the subject by gene editing ex vivo to increase the expression of the one or more protective protein variant(s) in the immune cells and/or hematopoietic stem cells, and administering the altered immune cells and/or hematopoietic stem cells to the subject, thereby treating the autoimmune disorder, wherein the autoimmune disorder is an autoimmune disorder that is treatable by increasing expression of one or more IL23 protective protein variants. The claim encompasses any method of ex vivo gene editing to alter immune cells and/or hematopoietic stem cells at any location by any gene editing technique including those may not increase expression of any IL23R protective protein variant and those that may not increase the expression of IL23 protective protein variants in the subject.
It is noted that the instant rejection is based on the following issue three issues: absence of an enabling disclosure for treating a subject having an autoimmune disorder that is treatable by increasing expression of one or more IL23 protective protein variants (issue i) by increasing the expression of any of the claimed protective protein variants (issue ii) by altering immune cells and/or hematopoietic cells stem cells at any location (issue iii) by any gene editing method (issue iv).
Specification Guidance: The specification describes the present invention provides methods and compositions for treating or preventing an autoimmune disorder in a subject and some aspects relate to methods for the treatment wherein the risk or symptoms are reduced by editing of relevant tissue involved in the disease causing process, to add protective mutations and/or remove susceptibility mutations (page 11, para. 0038). Some aspects involve the use of gene editing to edit the genes of the immune cells, or the tissue that generates the immune cells by hematopoiesis, which give rise to the inflammatory immune response. By changing the underlying genes to eliminate risk alleles, and/or create protective alleles, the complex gene signaling pathways do not need to be precisely understood in order to eliminate or reduce the severity of the autoimmune phenotype (page 14, para. 0048). The specification provides guidance on how to identify protective variants in genes, which is similar to identifying susceptibility genes, and includes identifying the protective variant based on family tree and phenotype of family members, whole exome or whole genome sequencing, computer simulations of cellular signaling or of an immune response, machine modeling, and animal models (page 12 – 13, para. 0042; page 15, para. 0052). The specification teaches the methods and compositions that can be used to make desired genetic modifications may comprise a nuclease, such as CRISPR system, a zinc finger nuclease system, a TALEN, a meganuclease, or a RNAi system (page 19, para. 0061; page 19 – 27).
Working Examples: Example 1 describes mice are either chemically treated or genetically modified to induce inflammatory bowel disease (page 29, para. 0093). Example 1 describes CRISPR/Cas9 gene editing mouse embryos to provide the heterozygous IL-10 susceptibility mutation (page 29, para. 0095; page 30, para. 0096; page 35, para. 0110 – 0112).
Regarding the claimed breadth of altering immune cells and/or hematopoietic stem cells at any location by any gene editing method (issues iii and iv), Example 1 describes the use of gene editing by CRISPR/Cas9 editing where the Cas9 protein and guide RNA (gRNA) is able to bind to a particular target DNA that matches the gRNA and cut the DNA at both strands that either causes the target DNA to be replaced by the replacement DNA, or initiates a process of homologous repair in the cell, where the corresponding DNA in the homologous chromosome or template DNA is copied to repair the cut DNA (page 28 – 29, para. 0092; page 31, para. 0100). Mice are generated by CRISPR/Cas9 editing to confer a protective mutation to the IL23R gene with gRNA designed to attach to DNA that encodes the IL23R amino acid SEQ ID NO: 1 where the DNA sequence is set forth in SEQ ID NO: 2 (page 30, para. 0096; page 32 – 33, para. 0102). The CRISPR/Cas9 complex is designed to cleave the DNA in the region of the R at position 381 and the template DNA is designed to achieve homologous repair so that the R at position 381 is converted to a Q, or the G at nucleotide position 1142A is converted to an A with template DNA of SEQ ID NO: 2 (page 33, para. 0103). Guide RNA templates are designed to target particular regions of the IL23R gene with gRNA sequences for mouse and human given in SEQ ID NO: 3 – 36). Thus the working example provides markedly narrower guidance than encompassed by the breadth of “altering immune cells and/or hematopoietic cells” at any location by “gene editing” by any method recited in claim 1.
Regarding lack of an enabling disclosure for treating a subject (issue i) and increasing the expression of any of the claimed protective protein variants (issue ii), Example 1 teaches a prophetic example of creating groups of mice having a susceptibility mutation in IL10 (Group A), having the IL10 susceptibility mutation and the IL23R protective mutation (Group C), having only the IL23R protective mutation (Group D), and having no mutations (Group B) (page 29, para. 0095). Example 1 teaches in mice for which HSCs are edited, HSCs are harvested from the bone or blood by capturing CD34+ cells and the harvested cells are then edited ex vivo and returned to the blood stream of mice that have had their native HSC population substantially depleted where roughly 1 million edited HSCs are injected each day for 3 days (page 30). Example 1 teaches roughly 24 weeks after transplant counting immune cells that carry the relevant edits to determine whether the engraftment of the edited HSCs was successful (page 30, para. 0098). Group A mice are edited to add the protective mutation (Group A2 and A3) and Group B mice are edited to add the protective mutation (Group B2) (“increase expression of the one or more protective protein variants “) and after waiting for the edited HSCs to generate immune cells (~6 months) and assuming engraftment in the edited groups are successful the mice are chemically induced for colitis and if the HSC editing was perfectly efficient, it is hypothesized that Group A2 mice should have a symptom level of 3 and Group A3 mice should have a symptom level of 1 compared to Group A mice that should have a symptom level of 4; Group B2 mice should have a symptom level of 1 compared to Group B mice that should have a symptom level of 3, where 4 is the worst symptom levels are ordered from 4 to 1 as worst to least (page 31, para. 0100; Table 1). Therefore, Example 1 provides a hypothesis that the symptoms of inflammatory bowel disease/colitis may be reduced by performing hematopoietic stem cell transplantation but also teaches the unpredictability of the method because no in vivo results of “treating” are provided nor are any in vitro results showing any increase in any IL23R protective protein variant that may be used to extrapolate to in vivo results. Further the specification teaches the unpredictability of the method by stating “whether the engraftment of the edited HSCs was successful” and “assuming the engraftment in the edited groups are successful” and that Table 1 shows “theoretically edited genetic status and one possible grouping of symptom levels” (page 30, para. 0098; page 31, para. 0101).
Thus the specification’s guidance and working example provide markedly narrower guidance than encompassed by the breadth of the claims and teaches the unpredictability of the method. Specific guidance to any other method that increases the expression of any IL23R protective protein variant is lacking because the specification only teaches CRISPR/Cas9 with guide RNAs having complementary sequences to codon 381 or 149 or 362 in the IL23R gene because the described methodology and working example only teaches CRISPR/Cas9 using site-specific guide RNAs to produce immune cells and/or hematopoietic stem cells with increased expression of R381Q or G149R or V362I IL23R protein variants. Enablement of the method is lacking because the specification only provides a hypothesis that increasing the expression of an IL23R protective variant may reduce symptoms as one possible grouping of symptom levels for increasing the expression of an IL23R protective variant.
State of the Art: Regarding the claimed breadth of gene editing at any location (issues iii and iv), the state of the prior art teaches CRISPR/Cas9 can be used for genome editing and uses guide RNA to precisely direct Cas9 to target sites where Cas9 produces breaks in DNA. The CRISPR/Cas9 system where Cas9 is co-expressed with custom guide RNAs has been successfully used in a variety of cells and organisms. However, there are several aspects that affect its efficiency and specificity including Cas9 activity and guide RNA design. Among the potential pitfalls of CRISPR/Cas9 systems, guide RNA is a prime concern because genome editing requires the design of guide RNAs that are efficient and specific and this remains a major challenge. The prior art teaches that not all guide RNAs are efficient or even active for genome editing. The prior art teaches that computational tools can facilitate the design of guide RNAs and most support the Cas9 system (Peng, Rongxue, et. al. The FEBS journal 283.7 (2016): 1218-1231; page 1223, left col. para. 2 – 4 and right col. para. 2; Table 1; previously cited). Thus, the prior art teaches that the CRIPSR/Cas9 method can be used for genome editing but requires custom guide RNAs that are active and precisely direct Cas9 to target sites. Further, the prior art teaches that computational tools are available to design guide RNAs but not all of the resulting guide RNAs are efficient or even active for genome editing. Therefore, the prior art teaches the unpredictability of the claimed breadth of any gene editing to increase expression of an IL23R protective variant.
Regarding the lack of enablement for treating a subject by altering immune cells and/or hematopoietic cells (issue i and ii), Pidasheva (WO2012071436-A1; Filed 11/22/2011; Published 05/31/2012; previously cited) teaches IL23R variants including R381Q are protective in Crohn’s disease (page 3, para. 009). Pidasheva teaches autoimmune disorders are heterogeneous in nature and the R381 coding variant has been found at lower frequencies in disease-affected individuals (page 3, para. 0010). Pidasheva teaches the R381Q variant confers an approximately 3-fold protection against developing Crohn’s disease and psoriasis indicating a protective role or at least an association with a lower risk of developing these diseases (page 29, para. 0102). Pidasheva teaches treating a subject having an autoimmune disorder with an IL-23R loss-of-function (LOF) mutation where the mutation may be R381Q by administering an agent other than an IL-23 pathway antagonist and treating a subject having an autoimmune disorder without an IL-23R LOF mutation with an agent that is an IL-23 pathway antagonist (page 4, para. 013 – 015; page 42, para. 0142). While Pidasheva teaches mutating R381 to Q in T cells in vitro results in a decreased population of IL-23 responsive cells, manifesting in diminished IL-23 dependent activation of all STATs known to be associated with IL-23 signaling (page 65, para. 0219), Pidasheva does not teach altering IL23R in a subject to treat an autoimmune disease. Thus, Pidasheva teaches the unpredictability of increasing the expression of an IL23R protective variant for treating an autoimmune disorder such as Crohn’s disease because Pidasheva teaches patients with Crohn’s disease may have the R381Q mutation and are treated with an agent other than an IL-23 pathway antagonist.
Regarding the lack of enablement for increasing the expression of an IL23R protective variant (issue ii) to increase the expression of the one or more IL23R protective variants, the state of the prior art teaches that the R381Q, G149R, and V362 IL23R protein variants cause a reduction in IL23R activation-mediated phosphorylation of STAT3 and STAT4 because of lower levels of cell surface expression. R381Q and V362I degrade rapidly, and the rate of synthesis of the variants is impaired in lymphoblastoid cell lines derived from individuals having these mutations. The data suggest that these protective variants have reduced activity due to reduced cell surface expression of mature receptors either due to reduced stability and/or impaired trafficking from the ER. Reduced surface expression resulted in reduced IL23-mediated signaling, such that all protective variants negatively impact IL-23 signaling (Sivanesan, Durga, et al. "IL23R (interleukin 23 receptor) variants protective against inflammatory bowel diseases (IBD) display loss of function due to impaired protein stability and intracellular trafficking." Journal of Biological Chemistry 291.16 (2016): 8673-8685; Abstract; page 8679, left col. para. 1 – 2 and right col. last para.; Figure 5; Figure 8; page 8680, left col. and right col.; Figure 9 – 10; page 8681, left col. para. 1 and right col. last para.; which is cited on the IDS filed 05/11/2023). Thus, the prior art teaches the mutagenesis of the wild type IL23R by site-directed mutagenesis alters the expression of IL23R by reducing expression of the IL23R protective variants thus leading to reduced IL23R-mediated signaling.
Amount of Experimentation: An application fails the enablement requirement if the experimentation needed to practice the invention is undue, not whether any experimentation is necessary. The amount of experimentation would be undue to practice the claimed method because the specification does not provide a reasonable amount of direction or guidance for experimentation and the experimentation that would be required is not routine. The specification’s teaching itself is evidence that at least a significant amount of experimentation would have been necessary to practice the claimed invention because the specification provides a hypothesis to be tested. While the prior art teaches IL23R variants including R381Q are protective in Crohn’s disease, the prior art also teaches that patients with autoimmune disease can have this IL23R variant. Therefore, further discovery experimentation would be required to determine if the recited IL23R variants would actually be therapeutic. Given the art teaches unpredictability and the specification provides no guidance to overcome this and given that the basis of the invention is an association that would require more experimentation to determine if there could possibly be any therapeutic effect on an autoimmune disorder, the level of experimentation goes beyond routine optimization of an enabled concept to discover if the method of the invention can be enabled. This type of experimentation is undue.
Thus the breadth of the claims encompassing a method of gene editing immune and/or hematopoietic stem cells to increase expression of an IL23R protective variant to treat a subject with an autoimmune disease that is treatable by increasing expression of one or more IL23 protective protein variants lacks enablement because the specification solely provides specific guidance to making the protective variants by CRISPR/Cas9 with guide RNAs with specific sequences complementary to sites R381, G149, and V362 and because the specification only provides a prophetic example of treating irritable bowel disease that depends upon the unpredictability of “whether the engraftment of the edited HSCs was successful” and “assuming the engraftment in the edited groups are successful” and “theoretically edited genetic status and one possible grouping of symptom levels” (page 30, para. 0098; page 31, para. 0101). Further the art teaches there are multiple potential pitfalls for genome editing with CRISPR/Cas including the sequence of the guide RNAs and the efficiency of recombination, patients with Crohn’s disease may have a protective IL23R variant, and any protective effect of IL23R variants against autoimmune disease comes from their reduced expression. The art teaches that R381Q, G149R, and V362I IL23R variant show reduced cell surface expression. Therefore at the time of filing the skilled artisan would need to perform an undue amount of experimentation without a predictable degree of success to implement the invention as claimed.
Rejections Necessitated by Amendment
Duplicate Claims Warning
6. Applicant is advised that should claim 1 be found allowable, claim 31 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Both claims 1 and 31 recite essentially identical limitations because while claim 1 does not recite “obtaining immune cells…” of claim 31, both claims require gene editing and as claim 31 depends from claim 1, the gene editing is required to be ex vivo.
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.
7. Claim 1 is 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. 37 CFR 1.118 (a) states that “No amendment shall introduce new matter into the disclosure of an application after the filing date of the application”.
Claim 1 is drawn to method of treating a subject having an autoimmune disorder, the method comprising increasing in the subject an expression of one or more IL23R protein variants protective against the autoimmune disorder ("protective protein variant(s)"), the protective protein variant comprising one or more of a R381Q mutation, a Gl49R mutation, and a V362I mutation as compared to a corresponding wild type IL23R protein, wherein the increasing the expression of the one or more protective protein variants comprises: altering immune cells and/or hematopoietic stem cells in the subject by gene editing ex vivo to increase the expression of the one or more protective protein variant(s) in the immune cells and/or hematopoietic stem cells, and administering the altered immune cells and/or hematopoietic stem cells to the subject, thereby treating the autoimmune disorder, wherein the autoimmune disorder is an inflammatory disease treatable by increasing expression of one or more IL23 protective protein variants in the subject.
The specification provides no implicit or explicit support for the context of the breadth of “one or more IL23 protective protein variants” recited in line 14. The specification has only provided support for IL23R protective protein variants. Applicant states in REMARKS that support for the amendment to claim 1 can be found in the specification at para. 0055. However, paragraph 0055 does not recite IL23 protective protein variants. Applicants are reminded that it is their burden to show where the specification supports any amendments to the claims. See 37 CFR 1.121 (b)(2)(iii), the MPEP 714.02, 3rd paragraph, last sentence and also the MPEP 2163.07, last sentence.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure [or point to case law supporting incorporation of such a limitation as in the instant case]” (emphasis added).
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.
8. Claims 1, 2, 4, 5, 7, 9, 10, and 31 – 36 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.
9. Claim 1 recites “one or more IL23R protein variants” in line 2 and then recites “the protective protein variant comprising” in lines 3 – 4, and then recites “one or more IL23 protective protein variants” in line 14. It is unclear if “one or more IL23 protective protein variants” in line 14 refers to the IL23R protein variants (where IL23R refers to IL23 receptor protein) recited in line 2 or refers to variants of IL23 (the cytokine and not the receptor protein for the cytokine IL23). Claims 2, 4, 5, 7, 9, 10, and 31 – 36 are also rejected as they depend from claim 1 and do not clarify the grounds of rejection.
10. Regarding claim 36, it is unclear if “one or more IL23 protective protein variants” in line 2 refers to the IL23R protein variants (where IL23R refers to IL23 receptor protein) recited in line 2 of claim 1 or refers to variants of IL23 (the cytokine and not the receptor protein for the cytokine IL23).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
11. Claim 31 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 31 fails to further limit claim 1 because all of the limitations of claim 31 are recited in claim 1. While claim 1 does not recite “obtaining” as recited in claim 31, because claim 1 recites “gene editing ex vivo”, the claim requires obtaining cells from the subject. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Applicant’s Arguments/ Response to Arguments
12. Applicant Argues: Applicant asserts that the specification fully satisfies the requirement for enablement for the claimed “microorganisms”. Applicant asserts that the enablement rejection is moot because the specification enables amended claim 1. Applicant asserts that one need not necessarily disclose how to make each and every embodiment even in unpredictable arts. Applicant asserts that the applicable standard to determine what constitutes under experimentation is reasonableness and provided that an effect is sufficiently demonstrated in the specification to characterize a generic invention, every permutation within a generally operable invention does not need to be demonstrated in order for an inventor to obtain a generic claim. Applicant asserts that the specification provides a prophetic example that describes increasing in a subject the R381Q protective protein variant.
Response to Arguments: Applicant's arguments filed 05/11/2026 have been fully considered but they are not persuasive. Applicant has not provided any evidence for “treating a subject having an autoimmune disorder” broadly recited in claim 1. The describes a prophetic example of ex vivo gene editing HSCs and returning these gene edited HSCs to mice but the specification does not provide any results that this increases expression of any IL23R variant compared or treats any autoimmune disorder. Therefore, the specification lacks any results that the prophetic example treats any autoimmune disorder that is an inflammatory disorder in vivo and merely hypothesizes that the prophetic example of gene editing will treat any autoimmune disorder. The specification lacks any in vitro results that ex vivo gene edited cells have increased expression of any IL23R protein variant or that the ex vivo gene edited cells have reduced inflammation. Therefore, the specification lacks any in vitro results from which in vivo results may be extrapolated. Therefore, the rejection of the claims for lack of enablement is maintained and new claims 35 and 36 are also rejected for lack of enablement.
Conclusion
No claims allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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