MODULATION OF CILIOGENESIS

§112 §DP

Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . DETAILED ACTION A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/30/2026 has been entered. Applicant indicates on the Request for Continued Examination (RCE) Transmittal, that the response of 3/30/2026 be considered. Claim status In the reply filed 3/30/2026, Applicant has amended Claims 1 and 13, and cancelled Claims 5, 7-9, 11. Claims 1-3, 6, 10, 13-14, and 22-24 are under consideration. Election/Restrictions Applicant’s election of the following species without traverse in the reply filed on 1/21/2025 has been acknowledged. Compound that binds, associates, or interacts with the TrxG-MLL complex. Rejoinder The species election requirement between compounds, as set forth in the Office action mailed on 11/21/2024, has been reconsidered. The species election requirement between compounds that bind, associate or interact with the PRC1 and/TrxG-MLL complexes and compounds that modulate expression of the R2R1 gene or protein is hereby withdrawn. Claims 2, 10, and 22-24, directed to previously non-elected species are no longer withdrawn from consideration. In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01. Objection to Specification The specification is objected to because this application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821 (a)(1) and (a)(2), wherein strands of four or more amino acids or ten or more nucleotides are required to be identified by a sequence identifier. However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 because sequences are set forth in the specification at pages 24- 28 lack sequence identifiers. Since the sequences are already present in the sequence listing (SEQ ID NOs:7-25), it would be remedial to amend the specification to include the appropriate sequence identifiers. Applicants are required to comply with all of the requirements of 37 CFR 1.821 - 1.825. New Claim Objections Claim 1 is objected to because of the following informalities: instant claim uses the abbreviation “R2R1”, which has not been spelled out upon first use. Although claims are allowed abbreviations, Applicant should only use abbreviations that are well known and would be clear to someone who had not read the invention description. Appropriate correction is required. Withdrawn 35 USC § 112(a) The prior rejection of Claims 1, 3, 6, 13, and 14 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 is withdrawn in light of Applicant’s amendments of Claim 1 to limit the method to a treatment of a loss of ciliogenesis, and to further describe compounds for the methods. However, the Examiner has reapplied the 112(a) rejection as a scope of enablement rejection. Claim Rejections - 35 USC § 112(a) (Scope of Enablement) 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 1-3, 6, 13-14, and 22-24 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 method for treating a disease and/or conditions of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound that comprises a fragment of a nucleic acid sequence of SEQ ID NO: 1-4, wherein the compound is an antisense oligonucleotide which reduces, inhibits and/or ablates the expression, function and/or activity of the R2R1, does not reasonably provide enablement for methods of treating or preventing (as per claim 22) a disease and/or conditions of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound that is: a protein comprising SEQ ID NO: 5 or 6, or a protein at least 95% identical to SEQ ID NO: 5 or 6, a fragment of SEQ ID NO: 5 or 6, or PRC1 and/or TrxG-MLL binding fragment of SEQ ID NO: 5 or 6; an antibody capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, an antigen capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, or a target binding fragment capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex; a nucleic acid sequence corresponding to SEQ ID NO: 1-4, or a nucleic acid sequence at least 70% identical to SEQ ID NO: 1-4, or a nucleic acid sequence corresponding to SEQ ID NO: 1-4 that is a PRC1 and/or TrxG-MLL binding fragment. and/or a genus of compounds that modulate or mimic the expression, function and/or activity of the R2R1 gene (as per claim 22). SCOPE OF THE INVENTION The breadth of the claims encompasses a genus of methods for treating or preventing (as per Claim 22) a disease and/or condition of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound that is: a protein comprising SEQ ID NO: 5 or 6, or a protein at least 95% identical to SEQ ID NO: 5 or 6, a fragment of SEQ ID NO: 5 or 6, or PRC1 and/or TrxG-MLL binding fragment of SEQ ID NO: 5 or 6; an antibody capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, an antigen capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, or a target binding fragment capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex; a nucleic acid sequence corresponding to SEQ ID NO: 1-4, or a nucleic acid sequence at least 70% identical to SEQ ID NO: 1-4, or a nucleic acid sequence corresponding to SEQ ID NO: 1-4 that is a PRC1 and/or TrxG-MLL binding fragment; and/or a genus of compounds that modulate or mimic the expression, function and/or activity of the R2R gene (as per claims 2 and 22). As discussed supra, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Dependent claim 3 encompasses a genus of compounds that bind to or associate with the R2R1 binding sites within the PRC1 and/or TrxG-MLL complex. Dependent claim 6 encompasses a genus of compounds that bind to or associate with the DPY-30 and/or ASH2L subunit of the TrxG-MLL complex. Dependent claims 13-14 and 23-24 encompass a genus of diseases and/or conditions of the pulmonary system, and/or airways caused by a loss of ciliogenesis to be treated and/or prevented (as per claims 23-24), which are limited to ciliopathies and COPD. The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below. The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention. ACTUAL REDUCTION TO PRACTICE The specification does not provide guidance for or a working example for methods of treating and/or preventing (as per Claim 22) a pulmonary and/or airways disease and/or condition caused a loss of ciliogenesis by administering to a subject a compound that is a protein and/or PRC1 and/or TrxG-MLL binding fragment thereof, antibody, antigen, or target binding fragment thereof capable of binding R2R1 or its binding site within PRC1 and/or TrxG-MLL binding fragment thereof, or nucleic acid and/or PRC1 and/or TrxG-MLL binding fragment thereof, or as broadly as claimed in Claim 1, or that modulates or mimics the expression, function and/or activity of the R2R1 gene as broadly as claimed in Claims 2 and 22, or binds to or associates between R2R1 and subunits of the PRC1 and/or TrxG-MLL complex as claimed in Claim 3, or binds to or associates with DPY-30 and/or ASH2L subunits in the TrxG-MLL complex as claimed in Claim 6. Additionally, although Applicant’s disclosure provides a cell culture system representative of treating a pulmonary or airway disease and/or condition caused by a loss ciliogenesis by delivering an shRNA compound that targets R2R1 (see more below), no working examples were provided that utilize a cell culture system representative of a pulmonary or airway disease and/or condition caused by a loss ciliogenesis by administering compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target R2R1, a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL complex, and/or that modulates or mimics the expression, function and/or activity of the R2R1 gene. By contrast, Applicant’s has demonstrated an in vitro protein/protein interaction between R2R1 (alias FAM25C) and the DPY-30 and ASH2L members of the TrxG-MLL complex, as well as RNF2 of the PRC1 complex. Specifically, Applicant has disclosed that by a yeast two hybrid screen that R2R1 was capable of interacting with RNF2 (4/7 hits) and DPY-30 (1/7 hits, data not shown) (p. 21, 3rd para.). Applicant goes on to demonstrate that when HA-tagged R2R1 is mixed in vitro with members of the PRC1 and/or TrxG-MLL complex, the anti-HA R2R1 can co-immunprecipitate RNF2, ASH2L and DPY-30 (Fig. 2, p. 22, 2nd para.). However, Applicant has not provided any compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target R2R1, a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL complex, and/or that modulates or mimics the expression, function and/or activity of the R2R1 gene. Furthermore, Applicant has not characterized this in vitro interaction in the relevant pulmonary and/or airway cells in culture or in vivo, in order to establish that using any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL, would have any predictably effect on PRC1 and/or TrxG-MLL function. In other words, Applicant has not characterized the function effects of these interactions that would predictably inform the ordinary artisan on how to make and use any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that would lead to a successful method of treating and/or preventing (as per Claim 22) a disease and/or condition of the pulmonary system and/or airways caused a loss of ciliogenesis. Finally, Applicant’s specification has demonstrated that shRNA inhibition of the R2R1 gene in primary bronchial epithelial cells (PBEC) upregulates genes associated with ciliogenesis and/or cilary movement which are also involved with COPD (Figures 3-9, 13-18 of the disclosure), and appears to increase number of ciliated PBECs from both normal and COPD patients (Figures 22 and 23). Thus, while an inhibitory nucleic acid such as a shRNA or antisense oligo that can specifically knock-down R2R1 appears to supports a method of treating diseases and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis (note that Claim 10 is not included in instant rejection), neither Applicant’s specification nor the prior art (see below) would allow the ordinary artisan to make and use any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 to predictably treat and/or prevent (as per Claim 22) a disease and/or condition of the pulmonary system and/or airways caused a loss of ciliogenesis. In light of this limited disclosure, Applicant’s claimed genus of methods suffer from a lack of scope of enablement on at least three grounds. First, the scope of Claim 1 includes (a) protein therapy with human R2R1 (i.e, SEQ ID NO:5) or mouse R2R1 (i.e., SEQ ID NO:6), or sequences at least 95% identical thereto. However, Applicant’s results with shRNA inhibition of R2R1 indicate that decreased R2R1 protein, not increased R2R1 protein, would increase the number of ciliated PBECs. Similarly, the scope of Claim 1 includes (c) gene overexpression of human R2R1 (i.e, SEQ ID NO:1 & 2) or mouse R2R1 (i.e., SEQ ID NOs:3 & 4), or sequences at least 70% identical thereto. However, Applicant’s results with shRNA inhibition of R2R1 indicate that decreased R2R1 gene, not increased R2R1 gene, would increase the number of ciliated PBECs. Similarly, the scope of Claim 22 (and Claim 6) is directed to compounds that upregulate (i.e., modulate) or mimic the expression, function and/or activity of the R2R gene. However, Applicant’s results with shRNA inhibition of R2R1 indicate that downregulate the R2R1 gene, not upregulating or mimicking the R2R1 gene, would increase the number of ciliated PBECs. Second, although there is some evidence that members of the PRC1 complex may contribute to ciliopathies (see more below), neither Applicant’s disclosure nor the prior art disclose that any member of the TrxG-MLL complex (i.e., ASH2L, or DPY-30) can regulated ciliogenesis. Furthermore, Applicant has not identified the functional effects of the putative R2R1 binding on PRC1 and/or TrxG-MLL activity on methyltransferase activity, and/or that these interactions occur in the nucleus of a pulmonary airway cell. Finally, Applicant has not provided sufficient guidance for the making and using a compound of Claim 1, (a), (b), or (c) that are PRC1 and/or TrxG-MLL binding fragments, or capable of binding to uncharacterized binding site(s) between R2R1 and the PRC1 and/or TrxG-MLL complex. Since Applicant has not identified the bind site(s) between R2R1 and the members of the PRC1 and/or TrxG-MLL complex, the ordinary artisan could not predictably make and use the claimed compound to treat and/or prevent a disease or condition caused by a loss of ciliogenesis. Furthermore, Applicant discloses that R2R1 is a nuclear protein (p. 32, 1st para.), yet the scope of the claims include the full length proteins of human and mouse R2R1 (i.e., SEQ ID NOs:1-4), as well as antibodies and antigens, with no predictable outcome on how or if these compounds could target a nuclear complex in a cell. STATE OF THE ART & QUANTITY OF EXPERIMENTATION The state of the art teaches that methods for treating and/or preventing a disease and/or condition of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound as broadly as claimed in Claims 1, 2, 3, 6, and 22 is not a highly successful technique or has highly variable results. Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in practicing the instant invention. Although the TrxG-MLL complex comprising components such as ASH2L and DPY-30 was known in the prior art for controlling histone methylation, it was not known to be involved in conditions associated with aberrant or defective ciliogenesis. Specifically, the prior art of Veazy et al. (Alc Res:Current Reviews, 2013;35(1):77-85) reviews the role of the TrxG-MLL complex with respect to general histone modification and epigenetic regulation (see Fig. 3 below), and teaches MLL was originally identified as playing a role in the development of different types of leukemia, but admits “very little information exists on individual TrxG proteins or their biochemical functions” (p. 82, 1st para.) PNG media_image1.png 834 1216 media_image1.png Greyscale Veazy states that the complex is thought to promote cell-specific patterns of gene expression by regulating global and gene-specific H3K4 methylation during early embryonic development as evidenced from MLL mouse gene knockouts, and that the proper functioning of TrxG complexes is indispensable to converting bivalent loci into an actively transcribed state required for neurogenesis, yet “much remains unknown regarding the temporal and tissue-specific regulatory evens these protein promote” (p. 83, 1st & 2nd para.). Thus, the prior art does not predict or reasonably suggest a compound that is a binding fragment of the TrxG-MLL complex that could predictably treat and/or prevent a disease and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis. In regard to the interaction between R2R1 and members of the TrxG-MLL complex, the prior art is silent with respect to such an interaction. Furthermore, based on other known protein interactions with the TrxG-MLL complex, the in vitro binding data provided by Applicant’s Fig. 2 does not provide an enabling disclosure for making and using a compound that targets the R2R1 binding site and/or is a binding fragment of the TrxG-MLL complex, nor compounds that modulates or mimics the expression, function and/or activity of the R2R1 gene with respect to the interactions with the TrxG-MLL complex. Specifically, the prior art of Ullius et al. (Nuc Acid Res, 2014, 42(11)6901-6020), see IDS filed 7/02/2021) demonstrated in vitro binding between MYC and ASH2L, but could not effect methyltransferase activity of the TrxG-MLL complex by deleting the in vitro interaction domain between ASH2L and MYC (p. 6906, col 2). Thus, the prior art indicates that making and using a compound that targets the binding site between R2R1 and a member of the TrxG-MLL complex was not predictable and would have required undue experimentation. In regard to R2R1 binding to members of the PRC1 complex, the PRC1 complex was also known in the prior art as acting as an E3 ubiquitin ligase. Specifically, the prior art of Veazy et al. (Alc Res:Current Reviews, 2013;35(1):77-85) reviews the role of the PRC1 complex with respect to general histone ubiquitination of lysine 119 on histone 2A (see Fig. 2A below): PNG media_image2.png 684 1055 media_image2.png Greyscale a Furthermore, in regard to the role of the PRC1 complex and ciliopathies, Gascue et al (J Cell Sci, 2011, 125, 1-14, see IDS filed 7/02/2021) identified an interaction between the RNF2 (i.e, RING1B) member of PRC1 complex and the cilia protein BBS7. However, Gascue teaches that the ubiquitination activity of the PRC1 complex targets a large number of gene associate with cell maintenance and homeostasis, and that when the activity of PRC1 complex was tested in cells with perturbed ciliary function, the results were mixed as to the effects of transcriptional regulation (p. 7, Discussion, 2nd para.). In other words, Gascue teaches the transcriptional repression by the PRC1 complex is affected by numerous factors, and the effects of a protein binding partner can not be predicted a priori. Thus, the prior art does not predict or reasonably suggest a compound that is a binding fragment of the PRC1 complex that could predictably treat and/or prevent a disease and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis. Moreover, even with modern screening techniques, the generation of such compounds capable of the claimed function based on the limited disclosure by the Applicant was not predictable. Specifically, the prior art of Arkin et al. (Assay Guidance Manual, 2012, Eli Lilly & Co) teaches that it has been difficult to identify small molecules, antibodies or peptide inhibitors of protein-protein interactions (PPI). Often sited reasons for this challenge include a) the flat nature of PPI interfaces, which sometimes lack deep grooves where small molecules can stick, b) large contact area at the interface, which often exceeds the surface area of a drug-sized molecule, and c) bias in the screening libraries (p. 1, Introduction). Arkin goes on to state that even with modern screening formats, the screening for PPI inhibitors can identify compounds with many mechanisms of inhibition, some of which are undesired, such as direct assay interference, nonspecific binding, and covalent modification. Moreover, PPI screens must be optimized for the used of detergents, because no one detergent removes all aggregates, as well as for the sensitivity to diluting compounds such as DMSO, and necessitate multiple orthogonal assays because compounds will interfere with assays in multiple ways, some of which are difficult to predict (pgs. 2-3, General Considerations). Finally, Arkin discloses that although a primary screen may produce a set of compounds that might be active, many of these compounds will not be optimizable into a qualified drug that can be used in a subject. Moreover, the screens suffer from artifactual mechanisms that lead to activity in the primary assay, but do not translate into in vivo activity. A well-described and very common example is compound aggregation, which can interfere with protein structure in a number of pathological ways (p. 18, Validating drug-like binding of PPI inhibitors). Since the prior art at the effective filing date of the present application did not provide guidance for a method of treating and/or preventing a disease and/or condition of the pulmonary system and/or airways caused by loss of ciliogenesis comprising administering a compound as broadly as claimed, it is incumbent upon the instant specification to do so. Finally in regard to claim 22, methods of “preventing” diseases and/or conditions are usually reserved for vaccines and/or infectious diseases, and no known compound has been identified that is able to prevent a disease and/or condition associated with a loss of ciliogenesis. There is no reason why one skilled in the art would expect a single compound to prevent all of the diverse aspects of the genus of claimed disease and conditions. The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention. CONCLUSION Since the art teaches that success of said method is prone to influence by multiple factors, and is highly unpredictable with respect to treating and/or preventing a disease and/or condition of the pulmonary system and/or airways caused by loss of ciliogenesis by administering to a subject a compound as broadly as claimed, and the specification does not provide ample guidance with respect to achieving the unexpected results, one would be burdened with undue experimentation to practice the claimed invention with any compound. Given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is require to make and use the invention beyond the scope of to treating a disease and/or condition of the pulmonary system and/or airways caused by loss of ciliogenesis by administering to a subject an RNAi or antisense oligo comprising a fragment of SEQ ID NOs:1-4. (Written Description) Claims 1-3, 6, 13-14, and 22-24 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Independent claims 1 and 22 encompass a genus of methods for treating and/or preventing (as per Claim 22) diseases and/or conditions of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound that is: a protein comprising SEQ ID NO: 5 or 6, or a protein at least 95% identical to SEQ ID NO: 5 or 6, a fragment of SEQ ID NO: 5 or 6, or PRC1 and/or TrxG-MLL binding fragment of SEQ ID NO: 5 or 6; an antibody capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, an antigen capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, or a target binding fragment capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex; a nucleic acid sequence corresponding to SEQ ID NO: 1-4, or a nucleic acid sequence at least 70% identical to SEQ ID NO: 1-4, or a nucleic acid sequence corresponding to SEQ ID NO: 1-4 that is a PRC1 and/or TrxG-MLL binding fragment. and/or a genus of compounds that modulate or mimic the expression, function and/or activity of the R2R1 gene (as per claim 22). However, Applicant’s disclosure has not demonstrated nor described a compound as broadly as claimed that treated a subject with any of the claimed diseases and/or conditions. Dependent claim 3 encompasses a genus of compounds that bind to or associate with the R2R1 binding sites within the PRC1 and/or TrxG-MLL complex. However, Applicant’s disclosure has not demonstrated nor described the binding sites between R2R1 and the PRC1 and/or TrxG-MLL complex, nor any protein or peptide fragment, or antibody, antigen or target binding fragment, or nucleic acid or binding fragment that is capable of targeting the interaction. Dependent claim 6 encompasses a genus of compounds that bind to or associate with the DPY-30 and/or ASH2L subunit of the TrxG-MLL complex. However, Applicant’s disclosure has not demonstrated nor described the binding sites between R2R1 and the TrxG-MLL complex, nor any protein or peptide fragment, or antibody, antigen or target binding fragment, or nucleic acid or binding fragment that is capable of targeting the interaction. Dependent claims 13 and 14 encompass a genus of diseases and/or conditions associated with a loss ciliogenesis to be treated and/or prevented, which are limited to ciliopathies such as COPD. However, Applicant’s disclosure has not demonstrated nor described a subject with any of the claimed ciliopathies that was treated by the claimed method. Under the new Written Description Guidelines for antigen binding proteins molecules, the Examiner is directed to determine whether one skilled in the art would recognize that the applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination: on 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been re-evaluated in view of that guidance. “[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04. ACTUAL REDUCTION TO PRACTICE The specification does not provide guidance for or a working example for methods of treating and/or preventing (as per Claim 22) a pulmonary and/or airways disease and/or condition caused a loss of ciliogenesis by administering to a subject a compound that is a protein and/or PRC1 and/or TrxG-MLL binding fragment thereof, antibody, antigen, or target binding fragment thereof capable of binding R2R1 or its binding site within PRC1 and/or TrxG-MLL binding fragment thereof, or nucleic acid and/or PRC1 and/or TrxG-MLL binding fragment thereof, or as broadly as claimed in Claim 1, or that modulates or mimics the expression, function and/or activity of the R2R1 gene as broadly as claimed in Claims 2 and 22, or binds to or associates between R2R1 and subunits of the PRC1 and/or TrxG-MLL complex as claimed in Claim 3, or binds to or associates with DPY-30 and/or ASH2L subunits in the TrxG-MLL complex as claimed in Claim 6. Additionally, although Applicant’s disclosure provides a cell culture system representative of treating a pulmonary or airway disease and/or condition caused by a loss ciliogenesis by delivering an shRNA compound that targets R2R1 (see more below), no working examples were provided that utilize a cell culture system representative of a pulmonary or airway disease and/or condition caused by a loss ciliogenesis by administering compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target R2R1, a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL complex, and/or that modulates or mimics the expression, function and/or activity of the R2R1 gene. By contrast, Applicant’s has demonstrated an in vitro protein/protein interaction between R2R1 (alias FAM25C) and the DPY-30 and ASH2L members of the TrxG-MLL complex, as well as RNF2 of the PRC1 complex. Specifically, Applicant has disclosed that by a yeast two hybrid screen that R2R1 was capable of interacting with RNF2 (4/7 hits) and DPY-30 (1/7 hits, data not shown) (p. 21, 3rd para.). Applicant goes on to demonstrate that when HA-tagged R2R1 is mixed in vitro with members of the PRC1 and/or TrxG-MLL complex, the anti-HA R2R1 can co-immunprecipitate RNF2, ASH2L and DPY-30 (Fig. 2, p. 22, 2nd para.). However, Applicant has not provided any compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target R2R1, a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL complex, and/or that modulates or mimics the expression, function and/or activity of the R2R1 gene. Furthermore, Applicant has not characterized this in vitro interaction in the relevant pulmonary and/or airway cells in culture or in vivo, in order to establish that using any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that target a binding site between R2R1 and members of the PRC1 and/or TrxG-MLL, would have any predictably effect on PRC1 and/or TrxG-MLL function. In other words, Applicant has not characterized the function effects of these interactions that would predictably inform the ordinary artisan on how to make and use any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 that would lead to a successful method of treating and/or preventing (as per Claim 22) a disease and/or condition of the pulmonary system and/or airways caused a loss of ciliogenesis. Finally, Applicant’s specification has demonstrated that shRNA inhibition of the R2R1 gene in primary bronchial epithelial cells (PBEC) upregulates genes associated with ciliogenesis and/or ciliary movement which are also involved with COPD (Figures 3-9, 13-18 of the disclosure), and appears to increase number of ciliated PBECs from both normal and COPD patients (Figures 22 and 23). Thus, while an inhibitory nucleic acid such as a shRNA or antisense oligo that can specifically knock-down R2R1 appears to supports a method of treating diseases and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis (note that Claim 10 is not included in instant rejection), neither Applicant’s specification nor the prior art (see below) would allow the ordinary artisan to make and use any of the compounds as broadly as claimed in Claims 1, 2, 3, 6, and 22 to predictably treat and/or prevent (as per Claim 22) a disease and/or condition of the pulmonary system and/or airways caused a loss of ciliogenesis. In light of this limited disclosure, Applicant’s claimed genus of methods suffer from a lack of scope of enablement on at least three grounds. First, the scope of Claim 1 includes (a) protein therapy with human R2R1 (i.e, SEQ ID NO:5) or mouse R2R1 (i.e., SEQ ID NO:6), or sequences at least 95% identical thereto. However, Applicant’s results with shRNA inhibition of R2R1 indicate that decreased R2R1 protein, not increased R2R1 protein, would increase the number of ciliated PBECs. Similarly, the scope of Claim 1 includes (c) gene overexpression of human R2R1 (i.e, SEQ ID NO:1 & 2) or mouse R2R1 (i.e., SEQ ID NOs:3 & 4), or sequences at least 70% identical thereto. However, Applicant’s results with shRNA inhibition of R2R1 indicate that decreased R2R1 gene, not increased R2R1 gene, would increase the number of ciliated PBECs. Similarly, the scope of Claim 22 (and Claim 6) is directed to compounds that upregulate (i.e., modulate) or mimic the expression, function and/or activity of the R2R gene. However, Applicant’s results with shRNA inhibition of R2R1 indicate that downregulate the R2R1 gene, not upregulating or mimicking the R2R1 gene, would increase the number of ciliated PBECs. Second, although there is some evidence that members of the PRC1 complex may contribute to ciliopathies (see more below), neither Applicant’s disclosure nor the prior art disclose that any member of the TrxG-MLL complex (i.e., ASH2L, or DPY-30) can regulated ciliogenesis. Furthermore, Applicant has not identified the functional effects of the putative R2R1 binding on PRC1 and/or TrxG-MLL activity on methyltransferase activity, and/or that these interactions occur in the nucleus of a pulmonary airway cell. Finally, Applicant has not provided sufficient guidance for the making and using a compound of Claim 1, (a), (b), or (c) that are PRC1 and/or TrxG-MLL binding fragments, or capable of binding to uncharacterized binding site(s) between R2R1 and the PRC1 and/or TrxG-MLL complex. Since Applicant has not identified the bind site(s) between R2R1 and the members of the PRC1 and/or TrxG-MLL complex, the ordinary artisan could not predictably make and use the claimed compound to treat and/or prevent a disease or condition caused by a loss of ciliogenesis. Furthermore, Applicant discloses that R2R1 is a nuclear protein (p. 32, 1st para.), yet the scope of the claims include the full length proteins of human and mouse R2R1 (i.e., SEQ ID NOs:1-4), as well as antibodies and antigens, with no predictable outcome on how or if these compounds could target a nuclear complex in a cell. DISCLOSURE OF STRUCTURE & RELEVANT IDENTIFYING CHARACTERISTICS The Applicant has provided the following amino acid sequence listings of SEQ ID NO for R2R1 proteins. PNG media_image3.png 133 1012 media_image3.png Greyscale PNG media_image4.png 142 1012 media_image4.png Greyscale Specifically, Applicant describes SEQ ID NOs:5 and 6 as corresponding to mouse and human R2R1 proteins, respectively, and asserts that these proteins or peptide fragments thereof bind, interact or otherwise associate with a component of the TrxG-MLL complex (p. 9. 3rd & 4th para.). Furthermore, Applicant has provided the following nucleic acid sequence listings of SEQ ID NO for R2R1 proteins: PNG media_image5.png 358 1006 media_image5.png Greyscale PNG media_image6.png 311 996 media_image6.png Greyscale Specifically, Applicant describes SEQ ID NOs:1-4 as corresponding to mouse (SEQ ID NO:2 is the underlined portion of SEQ ID NO:1) and human R2R1 genes (SEQ ID NO:4 is the underlined portion of SEQ ID NO:3), respectively, and asserts that these nucleic acids or fragments thereof encode proteins and peptides that correspond to any R2R1 binding site with a component of the PRC1 and/or TrxG-MLL complex (p. 6, 2nd para.). Applicant has provided no descriptions of an antibody, an antigen, or target binding fragment thereof capable of binding R2R1 or an R2R1 binding site within the PRC1 and/or TrxG-MLL complexes. MPEP 2163 states that “A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence”. Importantly, neither the specification nor the art indicate a relationship between the structure of the claimed genus of compounds and the ability to target the binding site between R2R1, associates or interacts with the TrxG-MLL complex, so as to interfere with, prevent or inhibit binding between R2R1 with a subunit of the TrxG-MLL complex so as to allow the treatment and/or prevention of a disease or condition of ciliogenesis Accordingly, if the skilled artisan sought to generate the claimed genus of compounds, they would first need to know which sequences in the R2R1 and PRC1 and/or TrxG-MLL complexes could be chosen to predictably produce a compound capable of the claimed function. Hence, based on the written description guidelines, the Examiner should conclude that the Applicant was not in possession of the claimed genus of compounds, and the present specification provides no guidance nor description to any rational in choosing the sequences that could achieve the claimed function. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the genus of compounds. An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. STATE OF THE ART & QUANTITY OF EXPERIMENTATION The state of the art teaches that methods for treating and/or preventing a disease and/or condition of the pulmonary system and/or airways caused by a loss of ciliogenesis by administering to a subject a compound as broadly as claimed in Claims 1, 2, 3, 6, and 22 is not a highly successful technique or has highly variable results. Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in practicing the instant invention. Although the TrxG-MLL complex comprising components such as ASH2L and DPY-30 was known in the prior art for controlling histone methylation, it was not known to be involved in conditions associated with aberrant or defective ciliogenesis. Specifically, the prior art of Veazy et al. (Alc Res:Current Reviews, 2013;35(1):77-85) reviews the role of the TrxG-MLL complex with respect to general histone modification and epigenetic regulation (see Fig. 3 below), and teaches MLL was originally identified as playing a role in the development of different types of leukemia, but admits “very little information exists on individual TrxG proteins or their biochemical functions” (p. 82, 1st para.) PNG media_image1.png 834 1216 media_image1.png Greyscale Veazy states that the complex is thought to promote cell-specific patterns of gene expression by regulating global and gene-specific H3K4 methylation during early embryonic development as evidenced from MLL mouse gene knockouts, and that the proper functioning of TrxG complexes is indispensable to converting bivalent loci into an actively transcribed state required for neurogenesis, yet “much remains unknown regarding the temporal and tissue-specific regulatory evens these protein promote” (p. 83, 1st & 2nd para.). Thus, the prior art does not predict or reasonably suggest a compound that is a binding fragment of the TrxG-MLL complex that could predictably treat and/or prevent a disease and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis. In regard to the interaction between R2R1 and members of the TrxG-MLL complex, the prior art is silent with respect to such an interaction. Furthermore, based on other known protein interactions with the TrxG-MLL complex, the in vitro binding data provided by Applicant’s Fig. 2 does not provide an enabling disclosure for making and using a compound that targets the R2R1 binding site and/or is a binding fragment of the TrxG-MLL complex, nor compounds that modulates or mimics the expression, function and/or activity of the R2R1 gene with respect to the interactions with the TrxG-MLL complex. Specifically, the prior art of Ullius et al. (Nuc Acid Res, 2014, 42(11)6901-6020), see IDS filed 7/02/2021) demonstrated in vitro binding between MYC and ASH2L, but could not effect methyltransferase activity of the TrxG-MLL complex by deleting the in vitro interaction domain between ASH2L and MYC (p. 6906, col 2). Thus, the prior art indicates that making and using a compound that targets the binding site between R2R1 and a member of the TrxG-MLL complex was not predictable and would have required undue experimentation. In regard to R2R1 binding to members of the PRC1 complex, the PRC1 complex was also known in the prior art as acting as an E3 ubiquitin ligase. Specifically, the prior art of Veazy et al. (Alc Res:Current Reviews, 2013;35(1):77-85) reviews the role of the PRC1 complex with respect to general histone ubiquitination of lysine 119 on histone 2A (see Fig. 2A below): PNG media_image2.png 684 1055 media_image2.png Greyscale a Furthermore, in regard to the role of the PRC1 complex and ciliopathies, Gascue et al (J Cell Sci, 2011, 125, 1-14, see IDS filed 7/02/2021) identified an interaction between the RNF2 (i.e, RING1B) member of PRC1 complex and the cilia protein BBS7. However, Gascue teaches that the ubiquitination activity of the PRC1 complex targets a large number of gene associate with cell maintenance and homeostasis, and that when the activity of PRC1 complex was tested in cells with perturbed ciliary function, the results were mixed as to the effects of transcriptional regulation (p. 7, Discussion, 2nd para.). In other words, Gascue teaches the transcriptional repression by the PRC1 complex is affected by numerous factors, and the effects of a protein binding partner can not be predicted a priori. Thus, the prior art does not predict or reasonably suggest a compound that is a binding fragment of the PRC1 complex that could predictably treat and/or prevent a disease and/or condition of the pulmonary system and/or airways caused by the loss of ciliogenesis. Moreover, even with modern screening techniques, the generation of such compounds capable of the claimed function based on the limited disclosure by the Applicant was not predictable. Specifically, the prior art of Arkin et al. (Assay Guidance Manual, 2012, Eli Lilly & Co) teaches that it has been difficult to identify small molecules, antibodies or peptide inhibitors of protein-protein interactions (PPI). Often sited reasons for this challenge include a) the flat nature of PPI interfaces, which sometimes lack deep grooves where small molecules can stick, b) large contact area at the interface, which often exceeds the surface area of a drug-sized molecule, and c) bias in the screening libraries (p. 1, Introduction). Arkin goes on to state that even with modern screening formats, the screening for PPI inhibitors can identify compounds with many mechanisms of inhibition, some of which are undesired, such as direct assay interference, nonspecific binding, and covalent modification. Moreover, PPI screens must be optimized for the used of detergents, because no one detergent removes all aggregates, as well as for the sensitivity to diluting compounds such as DMSO, and necessitate multiple orthogonal assays because compounds will interfere with assays in multiple ways, some of which are difficult to predict (pgs. 2-3, General Considerations). Finally, Arkin discloses that although a primary screen may produce a set of compounds that might be active, many of these compounds will not be optimizable into a qualified drug that can be used in a subject. Moreover, the screens suffer from artifactual mechanisms that lead to activity in the primary assay, but do not translate into in vivo activity. A well-described and very common example is compound aggregation, which can interfere with protein structure in a number of pathological ways (p. 18, Validating drug-like binding of PPI inhibitors). Since the prior art at the effective filing date of the present application did not provide guidance for a method of treating and/or preventing a disease and/or condition of the pulmonary system and/or airways caused by loss of ciliogenesis comprising administering a compound as broadly as claimed, it is incumbent upon the instant specification to do so. Finally in regard to claim 22, methods of “preventing” diseases and/or conditions are usually reserved for vaccines and/or infectious diseases, and no known compound has been identified that is able to prevent a disease and/or condition associated with a loss of ciliogenesis. There is no reason why one skilled in the art would expect a single compound to prevent all of the diverse aspects of the genus of claimed disease and conditions. Not knowing, absent further experimentation and screening, which compound predictably serves as a binding fragment or targets a binding site within the PRC1 and/or TrxG-MLL complex, leads to one having no predictability or expectation of success for the function of treating and/or preventing a disease and/or condition associated with aberrant or defective ciliogenesis. Such random experimentation to identify at a later time what structure or variant or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation. Furthermore, functionally defined genus claims (i.e., a binding fragment, capable of binding R2R1 or R2R1 binding site) can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). CONCLUSION Therefore, the examiner concludes that there is insufficient written description of the instantly claimed genus of methods and compounds. Specifically, there is limited description of the structure-function relationship between the claimed genus of compounds and their ability to be used in a method to treat and/or prevent diseases and/or conditions of the pulmonary system and/or airways caused by loss of ciliogenesis, and the Examiner further concludes a skilled artisan would find the specification inadequately describes the genus of compounds encompassed by the claimed methods. RESPONSE TO ARGUMENTS Applicant's arguments filed on 3/30/2026 are acknowledged. Applicant argues that instant methods of treating and/or prevent pulmonary and/or airway diseases and/or conditions that are caused by loss of ciliogenesis is now sufficiently enabled and described by the claim amendments directed to the types of compounds to be used. Furthermore, Applicant argues that the data provided by the specification adequately supports that there is an interaction between R2R1 and the RNF2 member of the PRC1 complex and DPY-30 and ASH2L of the TrxG-MLL complex. Furthermore, Applicant argues that the knock-down data for R2R1 adequately supports that R2R1 is an on/off switch for ciliogenesis. Applicant argues that the presented data sufficiently describe the functional effects of the interaction of R2R1 with the TrxG-MLL complex, wherein knock-down of R2R1 permits progression of pathways involved in ciliogenesis. Applicant argues that there is no need for an actual reduction to practice for a claimed invention, as long as the specification discloses at least one method for making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim. Furthermore, it is widely accepted that the effects of knock-down by RNAi, the ability to inhibit the same protein by another method (i.e., inhibitory fragments and/or antibodies) is also enabled. Applicant argues that the specification states that a peptide derived from R2R1 that interacts with the R2R1-RNF2 or R2R1-DPY30/ASHL binding site can restore ciliogenesis. Finally, Applicant argues for the novelty and inventiveness of the claimed method. Applicant argues that the specification for the first time presents a link between R2R1 and components of the PRC1/TrxG-MLL complex, and the role of these interactions in the modulation of ciliogenesis. As such, one of ordinary skill in the art at the time of filing would not even have a hint of these relationships. Applicant's arguments have been fully considered but they are not persuasive. First, in regard to Applicant’s arguments that the disclosure of knocking down R2R1 upregulating ciliogenesis sufficiently enables and describes the genus of compounds for disrupting the protein interactions of R2R1 is a clear scientific overreach. As stated previously, although siRNA, anti-sense oligos, gene disruption all reduce R2R1 function, they do so in a very generic manner (knock-down of the R2R1 protein). By contrast, Applicant is attempting to extrapolate the effects of a knock-down of R2R1 protein to particular protein interactions with the PRC1 and/or Trx-MLL complexes or subunits thereof with no evidence that these interactions affect ciliogenesis in any manner. Although the knock-down of R2R1 would also inhibit the interaction of R2R1 with the PRC1 and TrxG-MLL complexes, there is no manner to predict that the loss of these particular protein-protein interactions between R2R1 and members of the PRC1 and/or TrxG-MLL complex was necessary or sufficient to affect ciliogenesis, and neither Applicant’s disclosure nor the prior art would have predicted that inhibitory binding fragments or inhibitory antibodies of these protein interaction would have recapitulated the knock-down of R2R1. MPEP 2164.04 is clear that although a single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In reVickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In reCook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). Since applicant admits that the claimed method was unpredictable and that one of ordinary skill would have no hint to the interactions between R2R1 and members of the PRC1 and/or TrxG-MLL complex, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species (i.e., shRNA knock-down) usually does not provide an adequate basis to support generic claims. In reSoll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In reFisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In reWright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In reVaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because in art areas having a high degree of uncertainty (i.e. the unpredictable arts) it is not reasonably predictable from the disclosure of one species (e.g., shRNA), what other species will work (e.g., inhibitory peptide or inhibitory antibody between R2R1 and PRC1 and/or TrxG-MLL complex). Second, even if the scientific leap could have been predictably made between equating the function between R2R1 knock down and the disruption of the particular protein interactions of R2R1 with members of the PrC1 complex and/or TrxG MLL complex, contrary to applicant’s assertion no compounds for these particular functions are disclosed or sufficiently described by Applicant’s specification. As a first matter, neither Applicant’s disclosure nor the prior art describe that either TrxG, MLL, ASH2L, or DPY-30 can regulate ciliogenesis, much less be targeted by a genus of compounds to treat and/or prevent a disease or condition caused by the loss of ciliogenesis by interfering with the interaction of R2R1. Furthermore, in instances where there is prior art directed to the function of RNF2 and ciliogenesis, the nature of the protein binding partners with RNF2 have different effects on the transcriptional repression mediated by the PRC1 complex. As stated supra, Applicant has not characterized the functional effects of R2R1 binding to the PRC1 and/or TrxG-MLL complex. As a second matter, neither Applicant’s disclosure nor the prior art sufficiently describe the protein interaction between R2R1 and members of the PrC1 complex or TrxG-MLL complex that would allow one of ordinary skill to predictably make and use a compound which is a binding fragment or antibody that targets the binding sites between R2R1 and the PrC1 and/or TrxG-MLL complex so as to allow the treatment and/or prevention of a disease or condition caused by a loss of ciliogenesis. Finally, in regard to Applicant’s arguments that the cell culture findings with R2R1 knock down support a broader method with other types of inhibitors of R2R1, as well as inhibiting the interactions of R2R1 with members of the PRC1 and/or TrxG-MLL complex, Applicant’s claims are entirely silent to inhibiting these interactions. For example, Applicant generally claims proteins and nucleic acids that encode R2R1, antibodies that bind R2R1, and/or compounds that modulate or mimic R2R1. None of these claimed compounds are claimed to disrupt the interaction between R2R1 and members of the PRC1 and/or TrxG-MLL complex. Applicant is reminded that In Crossv.Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985), although the Federal Circuit affirmed that a pharmacological utility had been disclosed in the application, it was based on finding that Iizuka’s application had sufficiently disclosed a pharmacological utility for the compounds and it distinguished the case from cases where only a generalized “nebulous” expression, such as “biological properties,” had been disclosed in a specification. Such statements, the court held, “convey little explicit indication regarding the utility of a compound.” Cross, 753 F.2d at 1048, 224 USPQ at 745 (citing In re Kirk, 376 F.2d 936, 941, 153 USPQ 48, 52 (CCPA 1967)). In instant case, Applicant has not demonstrated the pharmacological utility of any compound in vitro or in vivo that is a protein or nucleic acid that encodes R2R1, antibodies that bind R2R1, and/or compounds that upregulate or mimic R2R1. New Claim Rejections - 35 USC § 112(b) The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 2, 3, 6 and 22 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 pre-AIA the applicant regards as the invention. Claim 2 recites the limitation wherein the compound “modulates or mimics the expression, function and/or activity of the R2R gene" in regard to compounds of Claim 1. There is insufficient antecedent basis for this limitation in the claim because although Claim 1 recites the compound either is a protein comprising SEQ ID NO: 5 or 6, or a protein at least 95% identical to SEQ ID NO: 5 or 6, a fragment of SEQ ID NO: 5 or 6, or PRC1 and/or TrxG-MLL binding fragment of SEQ ID NO: 5 or 6; an antibody capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, an antigen capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex, or a target binding fragment capable of binding R2R1 or an R2R1 binding site with the PRC1 and/orTrxG-MLL complex; or a nucleic acid sequence corresponding to SEQ ID NO: 1-4, or a nucleic acid sequence at least 70% identical to SEQ ID NO: 1-4, or a nucleic acid sequence corresponding to SEQ ID NO: 1-4 that is a PRC1 and/or TrxG-MLL binding fragment, it is unclear which of these compounds of Claim 1 are encompassed by the compounds of Claim 2. Similarly, Claim 3 recites the limitation wherein the compound “associates with” the R2R1 binding sites within the TrxG-MLL complex, which does not have a proper antecedence because is unclear which of the compounds of Claim 1 are encompassed by the compounds of Claim 3. Similarly, Claim 6 recites the limitation wherein the compound binds to or associate with the DPY-30 and/or ASH2L subunit of the TrxG-MLL complex, which does not have a proper antecedence because is unclear which of the compounds of Claim 1 are encompassed by the compounds of Claim 6. Claim 22 recites the limitation in the preamble that the method treats and/or prevents “the disease”. There is insufficient antecedent basis for this limitation in the claim because no disease had yet been recited in the claim. Appropriate correction is required. New Claim Rejections - 35 USC § 112(d) 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. Claim 10 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 10 draws to a method of treatment comprising administering a compound that is “an antisense oligonucleotide", which does NOT narrow the scope of claim 1 where the compound is a nucleic acid sequence corresponding to SEQ ID NO: 1-4, or a sequence that is at least 70% identical, PRC1 and/or TrxG-MLL binding fragment. In other words, SEQ ID NOs: 1-4 are nucleic acid sequences that are between 267 to 425 nucleotides and length, while antisense oligonucleotides only comprise between 5-50 contiguous nucleic acid residues of SEQ ID NO:1-4 (see p. 10, 3rd para. of Applicant’s specification describing antisense oligonucleotides and RNAi type inhibitors). Essentially, due to the Applicant’s own claim language and what is generally known about antisense oligonucleotides, the antisense oligo embodiment of claim 10 is excluded from the scope of nucleic acids of claim 1. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b). Claims 1-2, 10, 13-14, and 22-24 are rejected on the grounds of nonstatutory double patenting over claims 1-5 of U.S. Patent No. 11,007,131 (Van Brempt, Patented 8/03/2021). The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for treating a loss of ciliogenesis comprising administering a compound comprising an antisense oligonucleotide or RNAi type inhibitor cited patent anticipates and/or makes obvious the method instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are more specific to the compound. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Since the instant application claims are anticipated by and/or obvious over cited patent claims, said claims are not patentably distinct. Conclusion No claims are allowed. Examiner Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ARTHUR S LEONARD/Examiner, Art Unit 1631