Detailed Action
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-28 and 36-37 are cancelled.
Applicant’s election without traverse of Group III (claims 35-37) and the species of Pellino-1 protein in the reply filed on 02/09/2026 is re-acknowledged. Where the elected species of Pellino-1 protein is free from the prior art, the alternative non-elected species of the gene encoding pellino-1 protein is rejoined. Thus, the species election presented in the restriction requirement dated 12/09/2025 is withdrawn. The restriction requirement between groups/inventions presented in the restriction requirement dated 12/09/2025 is maintained as the elected claims are not deemed in condition for allowance.
Claims 29-34 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups/Inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/09/2026.
Claim 35 is amended.
Claim 38 is new.
Claims 29-35 and 38 are pending.
Claims 35 and 38 are under examination on the merits.
Maintained-NOTICE
No Power of Attorney has been filed for the instant Application. Clarification regarding representation or a lack thereof is request with an indicated contact person/entity to whom communications regarding the instant Application are authorized to be directed to promote compact prosecution.
Priority
This application is a 371 of PCT/KR2021/015902, filed 11/04/2021, which claims priority to REPUBLIC OF KOREA Application No. 10-2020-0146788, filed 11/05/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections/Rejections
The objection to the specification is withdrawn in light of the corrective amendments made 08/14/2026. All objections/rejections of claims 36-37 are withdrawn as moot in light of the cancellation of the claims via the 08/14/2026 claim amendments. The rejections of the claims under 35 USC §112(b) are withdrawn in light of the corrective claim amendments dated 08/14/2026.
Maintained-Claim Interpretation
Recitations of an “effective amount” are being interpreted according to the instant specification at exemplary paragraphs 142-143 at pages 26-27.
Recitations of an administration of an agent for reducing Pellino-1 protein expression are being interpreted according to the instant specification at exemplary paragraph 122 at page 22.
New-Claim Interpretation
Where claim 35 recited that the “agent is selected from the group consisting of an antisense nucleotide, siRNA, shRNA and ribozyme that complementarily binds to a gene encoding the Pellino-1 protein comprising the amino acid sequence of SEQ ID NO: 1,” it is noted that SEQ ID NO: 1 is the Pellino-1 protein, not a structure of the agent (see for example, paragraph 0032 at page 6 of the instant specification).
Maintained, but adjusted to account for narrowing amendments-Claim Rejections - 35 USC § 112
35 USC § 112(a)
Written Description
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 35 and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B. V. v. Dianwnd Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. This is a written description rejection.
Claim 35 is directed to a method of treating osteopetrosis comprising a step of administering an effective amount of an agent to a subject in need thereof, wherein the agent is for reducing the expression level of Pellino-1 protein).
The Application claims broad genera of agents. Therefore, in view of this disclosure, Applicant is claiming broad genera of agents (for reducing expression of either the PELI1 protein by binding SEQ ID NO: 1) and without a representative number of species of said genus of agents. The specification does not provide adequate written description for the entire claimed genus of species of agents as claimed, because in the absence of empirical determination, one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which agents would function to treat osteopetrosis and to bind SEQ ID NO: 1.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Applicant has not disclosed any such agent. It is noted that such an agent could be any number of biological species, such as an aptamer, shRNA, siRNA, etc. Thus, given the substantial structure variation within the genus as well as the high level of unpredictability in the art, the disclosure of no species of agent binds SEQ ID NO: 1 and treats osteopetrosis is not sufficiently representative of the entire genus of agents claimed.
Furthermore, Applicant has not disclosed relevant, identifying characteristics of agent amino acid or nucleic acid sequences that confer upon an agent the ability to function as claimed because the instant specification does not provide structural features that correlate with a functional ability to bind SEQ ID NO: 1 and treat osteopetrosis.
Absent a clear description of the at least minimal structural features correlating with a functional ability to bind SEQ ID NO: 1 and treat osteopetrosis as claimed which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which agents would possess the ability to function as claimed.
Furthermore, regarding nucleic acid-based genera of agents recited, Beauchamp et al (Why Can't We Predict RNA Structure At Atomic Resolution?, Arxic, DOI: 10.48550/arXiv.1103.3032 obtained from: https://ui.adsabs.harvard.edu/abs/2011arXiv1103.3032B/abstract (pub: 2011)) teach that no existing algorithm can start with arbitrary RNA sequences and return the precise, three-dimensional structures that ensures their biological function. Likewise, Watkins et al (Sci. Adv.4,eaar5316(2018).DOI:10.1126/sciadv.aar5316) teach that prediction of RNA structure from nucleotide sequence remains an unsolved grand challenge of biochemistry and requires distinct concepts from protein structure prediction. Despite extensive algorithmic development in recent years, modeling of noncanonical base pairs of new RNA structural motifs has not been achieved in blind challenges. Yang et al (Chemical Engineering Journal 538 (2026) 176731) support that the state of the art has not enabled predictable aptamer design from a known epitope. Yang et al teach that the performance of machine learning in aptamer engineering is critically dependent on high-quality, large-scale, and diverse training data. Currently, the field is hampered by a notable lack of standardized datasets, especially those containing reliable experimental measurements of binding affinity, structural conformation, or functional performance. Most available data are derived from high-throughput SELEX (HT-SELEX) experiments, which primarily provide enrichment statistics across selection rounds rather than direct biophysical parameters like dissociation constant (Kd) or thermodynamic binding profiles. Enrichment-based metrics are often used as proxies for affinity, but their reliability varies substantially depending on the SELEX protocol design, partitioning efficiency, and amplification bias. Moreover, many HT-SELEX datasets contain a large proportion of noisy, non-functional sequences, particularly in early rounds. This noise introduces uncertainty into supervised learning and complicates the extraction of consistent structure-function relationships. Another significant gap is the absence of well-defined benchmark datasets for evaluating model performance across diverse prediction tasks. Unlike protein modeling, where community benchmarks such as CASP, TAPE, or ProteinGym have facilitated robust method comparison and accelerated progress, aptamer research lacks curated datasets with consistent formatting, experimentally verified ground truth, and agreed-upon evaluation metrics. As a result, published models often use task-specific datasets with incompatible formats, limiting the reproducibility and generalizability of reported results. Many AI models for aptamer prediction report performance metrics that require careful interpretation. Cross-validation approaches vary significantly across studies, with some employing random sequence splits that may not reflect real-world generalization to novel targets or experimental conditions. Additionally, several high-performing models (AUROC >0.95) approach theoretical limits that warrant scrutiny for potential data leakage or overfitting. Reproducibility challenges also emerge after model nomination. Wet-lab performance can vary substantially across assay formats, buffer conditions, immobilization chemistries, and batch-specific synthesis quality, meaning that an aptamer validated in one laboratory may display attenuated affinity or altered specificity in another. Aptamer binding is governed not just by nucleotide sequence but also by secondary and tertiary structure, as well as by chemical modifications introduced during or after selection (see for example, sections 6-6.1). Despite this, many machine learning models in aptamer research still rely on primary sequence inputs alone (see for example, section 6.2). It is further established in the art that single point mutations are not independent from each other and the interactions between an aptamer and its target depend upon an intricate structure dictated by its sequence (Hasegawa H et al. Molecules 2016, 21(4), 421 pg. 1-15; https://doi.org/10.3390/molecules21040421, page 3, paragraph 2). Thus, mutations of aptamers can yield unpredictable results. Aptamers fold into unique structures that usually include stems and loops (Hasegawa, page 3, first paragraph). These structures are central to target molecule recognition and any disruptions result in poor binding abilities (Hasegawa, page 3, paragraph 2). Mutagenesis studies of IgE-binding aptamers showed point mutations at most positions within IgE aptamer sequences readily decreased the binding ability of aptamers (Hasegawa, page 2, last paragraph to page 3, first paragraph).
The specification does not disclose the structure of all of the claimed variant shRNAs, aptamers, siRNAs, etc, and fails to disclose which sequences are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of antibodies that would function in the method(s) as claimed, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
In Ariad, the court further noted that the written description plays a particularly important role in the biological arts, where patentees might otherwise be tempted to claim a genus of compounds by its function or result:
“The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts. 5 See Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, 1, “Written Description” Requirement, 66 Fed. Reg. 1099, 1105-1106 (Jan. 5, 2001). This situation arose not only in Eli Lilly but again in University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916 [69 USPQ2d 1886] (Fed. Cir. 2004). In Rochester, we held invalid claims directed to a method of selectively inhibiting the COX-2 enzyme by administering a non-steroidal compound that selectively inhibits the COX-2 enzyme. Id. at 918. We reasoned that because the specification did not describe any specific compound capable of performing the claimed method and the skilled artisan would not be able to identify any such compound based on the specification's function description, the specification did not provide an adequate written description of the claimed invention. Id. at 927-28. Such claims merely recite a description of the problem to be solved while claiming all solutions to it and, as in Eli Lilly and Ariad's claims, cover any compound later actually invented and determined to fall within the claim's functional boundaries—leaving it to the pharmaceutical industry to complete an unfinished invention.”
Ariad Pharmaceuticals., Inc. v. Eli Lilly & Co., 94 USPQ2d 1161, 1173 (Fed. Cir. 2010) (en banc). Emphasis added.
Applicant is further directed to In re Alonso (545 F.3d 1015 (Fed. Cir. 2008), which
involved claims that were directed to methods of using antibodies wherein the court found that
the claims lacked adequate written description for the recited genus of antibodies recited in the
methods. (C) See p. 8, 3rd paragraph, where Applicant argues that the claims recite all essential
features of the invention. Therefore, products used in methods are rightfully subject to the written
description requirement.
The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
Amgen and Ariad are seen as pertinent because, while the binding agents claimed are nucleic acid products, the understanding that the entirety of the genus of binding paratopes is not immediately described by nor reasonable should be tied up by disclosure of the epitope remains pertinent and the reasoning of the court is deemed to be instructive in this case.
Therefore, the agents, as claimed are only disclosed by function/insufficient structure, without a representative number of species or unifying, conserved structure clearly enabling one skilled in the art to readily envisage the members of the genus claimed which would function as claimed in the claimed method(s). Similarly, the artisan could not envisage readily which bin-related diseases would function as claimed (be treated by the method as recited in claims 35-37). Therefore, claims 35 and 38 are deemed to fail to meet the written description requirement, as presently drafted.
Maintained-Enablement
Claims 35 and 38 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.
MPEP 2164.01(a) states that in order to determine compliance with the enablement requirement, the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.”
These factors include but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
Claims 35 and 38 are directed to a method of treating bone-related disease comprising a step of administering an effective amount of an agent to a subject in need thereof, wherein the agent is for reducing the expression level of Pellino-1 protein or the gene encoding the protein.
This encompasses a broad range of bone-related diseases and agents.
The nature of the invention
Claims 35-37 are broadly directed to a method for treating bone-related disease. The claims are directed to biological subject matter which is understood to be complex and often unpredictable.
The state of the prior art
The state of the prior art supports that the development of PELI1 inhibitors is still in its early stages (see Synapse by Patsnap (obtained from: https://synapse.patsnap.com/article/what-are-peli1-inhibitors-and-how-do-they-work)(2024)). CorCon International (obtained from: https://corconinternational.com/bone-diseases-what-they-are-symptoms-and-treatment/ (accessed 05/04/2026)) teaches that bone diseases are highly heterogenous and therapeutic management depends on the specific condition to be treated and, of course, its severity. Bailey et al ([Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557529/) teach that osteopetrosis is characterized and driven by dysfunctional osteoclasts (see for example, the sections titled Etiology and Pathophysiology). Bailey et al go on to teach that management of patients with osteopetrosis must be tailored to the individual patient. Treatment is predominantly supportive with no known cure and interprofessional care and surveillance are treatment mainstays (see for example, the Treatment/Management section of Bailey et al).
The level of one of ordinary skill
As the claims are directed to treatment of a bone-related disease, the artisan is presumed to be highly skilled, tending to have an advanced degree (such as a Ph.D. or an M.D.).
The level of predictability in the art
As discussed above, CorCon International teaches that bone diseases are highly heterogenous and therapeutic management depends on the specific condition to be treated and, of course, its severity. Bailey et al teach that osteopetrosis is characterized and driven by dysfunctional osteoclasts (see for example, the sections titled Etiology and Pathophysiology). Bailey et al go on to teach that management of patients with osteopetrosis must be tailored to the individual patient. Treatment is predominantly supportive with no known cure, and interprofessional care and surveillance are treatment mainstays (see for example, the Treatment/Management section of Bailey et al). Mundy et al (J Bone Miner Metab 14, 59–64 (1996). https://doi.org/10.1007/BF01768833; cited on the 05/04/2023 IDS as NPL citation 1) teach that there are at least 11 known variants of osteopetrosis (see for example, column 2 of page 59).
More generally, Sun et al (Acta Pharmaceutica Sinica B 2022;12(7):3049e3062) teach that ninety percent of clinical drug development fails despite implementation of many successful strategies. Sun et al further note that current drug optimization overly emphasizes potency/specificity using structure‒activity-relationship (SAR) but overlooks tissue exposure/selectivity in disease/normal tissues using structure‒tissue exposure/selectivity–relationship (STR), which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity (see for example, the abstract). Additionally, The Marshall Protocol (Differences between in vitro, in vivo, and in silico studies, obtained from: https://mpkb.org/home/patients/assessing_literature/in_vitro_studies (2015)) discuss the deficiencies in predictable translation of results from in vitro, in vivo, and in silico studies with respect to treatment of an organism (see reference, generally).
Additionally, Chen et al (BioRiv preprint posted February 6, 2022, ORCID: https://orcid.org/0000-0002-9534-6199; doi: https://doi.org/10.1101/2022.01.30.478394) teach that simple elevation of protein/gene expression level in a disease state does not mean the gene/protein is causal for the disease nor targeting it would be effective for therapeutic efficacy. The increase/decrease in expression might only suggest it is correlated with disease progression. Differentiating “causality” from “correlation” is a crucial step in identifying a promising disease target (see for example, the first paragraph of the Introduction at page 3). Furthermore, Bryant et al (THE LANCET, Infectious Diseases Vol 4 February 2004, https://doi.org/10.1016/S1473-3099(04)00930-2) teach that knowledge that a gene is expressed under a particular condition is not an answer in itself but only the first step in understanding. For example, whether expression of a gene is vital for host defense or involved in tissue injury requires further investigation. In addition, expression of a gene does not always translate into production of a protein. Although gene expression reveals nothing directly about translational and post-translational events, protein activation status alterations can and do frequently alter the expression of downstream target genes (see for example, column 2 of page 110).
(F) The amount of direction provided by the inventor
Applicant does not disclose a single instance of administering an agent that binds SEQ ID NO: 1 (understood to be for reducing PELI-1 protein expression). Applicant discloses limited data regarding knockdowns of the PELI1 gene. For example, after overexpressing, knocking down, and gradually inhibiting Pellino-1 in the HEK293T cell line in vitro, the specification provides that it was confirmed that the transcriptional activity of NFATc1 decreased when Pellino-1 was overexpressed, whereas the transcriptional activity of NFATc1 increased when Pellino-1 was knocked down (see for example, instant Figure 2A and 2B). Applicant discloses that the results confirm the transcriptional activity of osteoclast differentiation marker NFATc1 (see for example, Figures 2A-2C and pages 32-37 of the specification). However, the specification fails to provide any examples where an agent for reducing PELI-1 expression (expression of the protein or the gene encoding the protein by binding to SEQ ID NO: 1), or where said agent is administered for treating osteopetrosis. Thus, there is no more pertinent example or guidance to be discussed. Applicant instead discloses theory as to why administration of such an agent would function to treat a bone-related disease. There is further no reason to believe or data to support that administering an agent that binds SEQ ID NO: 1 (understood to be intended to reduce PELI1 (theoretically increasing differentiation into osteoclasts)) would function reliably as claimed to treat osteopetrosis.
The existence of working examples
There are no working examples provided in the instant disclosure because an agent that binds SEQ ID NO: 1 is never administered. The specification does not disclose administration of an agent. Only knockdown experiments are disclosed at a high level of generality, failing to mention that SEQ ID NO: 1 is bound or the structure of any specific agent or route of administration.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
The case is directed to biological subject matter, which is by nature complex. There are no working example provided and the state of the art fails to step in to provide enablement where the instant disclosure is lacking. The artisan would be forced into burdensome experimentation so as to effectively invent what applicant only suggests may be possible.
Thus, in light of the cited prior art, the instant disclosure is not enabling for a method of treating osteopetrosis comprising administering any generic agent for that binds SEQ ID NO: 1, for reducing PELI1 expression (protein of gene), due to the lack of evidence that osteopetrosis would be treated by such an agent.
Applicant’s Arguments and Responses:
A. Applicant seems to allege that the amendment to claim 35 narrows the claim scope to what is described in requesting withdrawal of the rejections under 35 USC 112(a) (see for example, pages 5-6 of the 08/14/2026 remarks).
Response: No structure is provided for the agent that binds to SEQ ID NO: 1 (Pellino 1 protein). There is no structure function correlation shared by the members of the genus of agents recited responsible for the function of binding and treating osteopetrosis. There are no examples whose structure is clearly disclosed (no representative number of species), let alone to which the claims could be considered limited. Therefore, the rejection of record as presented in this Office Action is maintained.
B. Applicant argues for withdrawal of the rejection for lack of enablement under 35 USC §112(a) (see pages 6-11 of the 08/14/2026 remarks).
Response: Applicant points to figures 2a-8. The figures which are most pertinent as figures 5-6 showing actual changes in bone amount control and knockdown mice. However, as pointed out in the art cited in the rejection for lack of enablement, there are at least 11 known variants of osteopetrosis where the osteoclasts may not only be deficient in number, but defective in function. As it is stated in the rejection, there is no working example showing administration of an agent within the claim scope that binds SEQ ID NO: 1 and treats osteopetrosis. It does not appear that the mice used suffer from osteopetrosis (as this is not clearly stated and the idiosyncratic naming of the mice precludes clear confirmation of the disease state of the mice used). Where the mice do not suffer osteopetrosis, it is not reasonable to conclude that the changes in bone resorption noted would be observed in the setting of osteopetrosis where the osteoclasts themselves may fail to function. Put another way, there is no evidence that increased differentiation into defective osteoclasts as seen in certain osteopetrotic phenotypes would translate into improved osteoclast function in the form of noted normative bone resorption. Therefore, Applicant’s burden to support enablement of the claimed method and to rebut the prima facie case presented in the rejection has not yet been met and the rejection as presented in this Office Action is maintained.
Conclusion
No claim is allowed.
As noted in the previous office action, there is no prior art teaching administration of an agent that binds SEQ ID NO: 1 of the PELI1 protein or gene for treating osteopetrosis so as to provide a reasonable expectation of success before the effective filing date of the present invention.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mo et al (Bone Joint Res. 2023 Feb;12(2):121-132. doi: 10.1302/2046-3758.122.BJR-2022-0214.R1-cited on the 05/04/2023 IDS) is relevant. Mo et al link PELI1 and increased resorption as first being investigated and surprisingly helpful in osteoarthritis. However, Mo et al is published in 2023 and is not available to serve as prior art in view of the latest available priority date (371 PCT filing dated 11/04/2021). Additionally, Mo et al only discuss knockdowns of PELI1 with respect to murine osteoarthrosis treatment and, therefore, are not deemed to provide enablement or a reasonable basis for administration of an agent as required by the claims.
Jeon et al (Cell Death Differ 24, 469–480 (2017). https://doi.org/10.1038/cdd.2016.143; citation 14 under NPL on the 05/04/2023 IDS) and Jang et al (J Biol Chem. 2011 Nov 11;286(45):39043-50. doi: 10.1074/jbc.M111.256768. Epub 2011 Sep 23; citation 15 under NPL on the 05/04/2023 IDS) are deemed relevant. Jeon et al teaches subcutaneous administration of an shRNA that reduces expression of the PELI1 gene to mice, which reduces GSK3ß (see for example, Figures 2-3 and their captions of Jeon et al at pages 472-473, noting figure 3, part e is of particular relevance). Note that shRNA is within the scope of agent for administration contemplated by Applicant (see for example, paragraph 96 at page 17 of the instant specification). Jang et al teach that GSK3ß is required for osteoclastogenesis and shows that overexpression of GSK3ß (or a mutant GSK3ß which is not inhibited/reduced by RANKL (GSK3ß-S9A)) results in an osteopetrotic phenotype (see for example, page 39043). This does not provide enablement or a reasonable expectation of success for treating osteopetrosis, let alone other bone-related diseases, using the shRNA of Jeon et al because there is no showing of causality (between PELI1 and development of osteopetrosis) or a showing of treatment, where there is reasonable and significant doubt that merely increasing the number of osteoclasts produced would result in fully functional osteoclasts where a defining feature of osteopetrosis is dysfunctional osteoclasts.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
