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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Information Disclosure Statement
The 4-page information disclosure statement (IDS) filed 8/25/2023 fails to comply with the provisions of 37 CFR 1.98 and MPEP § 609 because for the US Application, it does not comply with 37 CFR 1.98(a)(1)(ii) requiring a column that provides a space, next to each document to be considered, for the examiner’s initial. Further US application 13/876,367 listed on the IDS is the same as US Patent Application Publication 2013/0202610 (reference #9) on the 42-page IDS filed the same day. The clinical trials listed in that IDS are duplicates of those listed on the 42-page IDS filed the same day. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
References lined through in the IDS filed 8/25/2023 are either duplicates or the listing is so incomplete as to not comply with 37 CFR 1.98(b)(5) (e.g., #202 in the IDS filed 8/25/2023). As a result, these references have not been considered.
It is noted the WO 2009/149168 A2 cited in the IDS filed 8/25/2023 is titled: ”Casting Furnace Method and Apparatus”.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 36-48 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.
Claims 36-48 are drawn to a method of inducing regeneration of tendon tissue or promoting tendon repair in a patient having tendinopathy, comprising administering an effective amount of an anti-IL-17 antibody or antigen-binding fragment thereof, wherein the IL-17 antibody or antigen-binding fragment thereof binds to an epitope defined by particular amino acids of each of two mature human IL-17 protein chains forming the homodimer. Claim 48 further limits the antibody or antigen-binding fragment thereof by comprising a heavy chain (HC) and/or light chain (LC), variable domain thereof (VH and/or VL) or heavy and/or light chain CDR1-3 defined sequence. Thus, the instant claims encompass administration of a genus antibodies that bind to an epitope of a human IL-17 homodimer having two mature human IL-17 protein chains or an antibody that comprises only the recited heavy or light chain sequence(s). The specification teaches that exemplary anti-IL-17 antibody is secukinumab (AIN457, top of p. 8) which comprises HC/LC sequences of SEQ ID NOs: 14/15 and VH/VL of SEQ ID NO:8/10 recited in instant claim 48, which is disclosed in WO 2006/013107 (page 18, second paragraph, through p. 21, and Table 1).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factors present in the claims, are (i) a structural characteristic of an IL-17 antibody that “binds to an epitope of a human IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising “Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, lle127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain” (claims 36-47); or an antibody that comprises the HC, VH or HCDR1-3 and/or the LC, VL or LCDR1-3 (claims 48 and 49) and (ii) functional characteristics of binding human IL-17 (at specific residues) with a KD of about 100-200 pM and having an in vivo half-life of about 4 weeks.
The instant specification fails to disclose and there is no art-recognized correlation between the structure of the genus of IL-17 antibodies and the function of binding human IL-17(at specific residues) with a KD of about 100-200 pM and having an in vivo half-life of about 4 weeks. In other words, the specification does not teach what structure correlates with (i.e., results in) an IL-17 antibody with the claimed required functional characteristics.
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). This has not been done.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The antibody itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One skilled in the art could not readily envision a representative number of antibody species to support the genus. The instant specification has disclosed only one antibody, secukinumab, that meets the structural and functional limitations of the claims. The difficulty in predicting the structure of antibodies binding the same epitope is exemplified by Nair et al. (J. Immunol. 168:2371-2382, 2002), which identified three distinct antibodies that recognized the same epitope, a peptide antigen (p. 2371, beginning of col. 2), yet had different structures both within and outside the CDRs (Fig. 1). As stated under the Discussion heading on p. 2378, “Diverse Abs exhibit equivalent topologies while recognizing a common immunodominant peptide epitope in similar conformation”. Even more dramatically, Fadeel et al. (Intl. Immunol. 9(2):201-209, 1997, p. 207) found four distinct antibodies that bound the same linear epitope on Fas/Apo-1 protein: one induced apoptosis, one blocked the apoptosis induced by the first antibody without itself inducing apoptosis, and the other two had no effect.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant’s attention is directed to the decision in Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The court discussed whether an antibody is adequately described by describing a newly characterized antigen. Specifically, the court referred to the decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011). In that case, the patentee claimed a genus of antibodies containing a human variable region that has particularly desirable therapeutic properties: high affinity, neutralizing activity, and A2 specificity. Despite the fact that the specification disclosed human TNF-α protein, the court ruled that that the generic antibody claims at issue were invalid for lack of written description, despite the disclosure of the structures of more than one species of antibody encompassed by the genus. The fact pattern is similar to the instant case. Specifically, in the instant case amino acid positions of the human IL-17 antigen are identified (Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, lle127, Val128, His129 on one chain and Tyr48, Tyr44, Arg46, Ala79, Asp80 on another), while the specific structures for the anti-IL-17 antibodies are not. As in the court case, the instant claims recite a genus of anti-IL-17 antibodies that have a desirable property, i.e., binding to an epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, lle127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain with a KD of about 100-200 pM and an in vivo half-life of about 4 weeks. Following the finding in Centocor, the instant claims are found to lack adequate written description. The court in Amgen v. Sanofi citing Centocor again provides an analogy for the antibody-antigen relationship as not quite a lock and key relationship but rather providing a lock and then searching for a key on a ring with a million keys on it. The court concludes that the “newly characterized antigen” test flouts basic legal principles of the written description requirement, reasoning that section 112 requires a written description of the invention, whereas the newly characterized antigen test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. Accordingly, since the instant fact pattern fits the “newly characterized antigen” scenario, wherein the specification describes the structure of the target/antigen but not the structure of the genus of anti-IL-17 antibodies, the claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph.
Therefore, only an isolated antibody that binds human IL-17 and comprises the HC and LC, VH and VL, and/or HCDR1-3 and LCDR1-3 thereof, as recited in claim 48 (iii)(vii)(viii)(xi), but not the full breadth of the claims, meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
Claims 36-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, because the specification, while being enabling for a method of reducing tendinopathy inflammation comprising administering an antibody that binds to and neutralizes IL-17A, does not provide enablement for a method of inducing regeneration of tendon tissue or promoting tendon repair in a patient having tendinopathy comprising administering an anti-IL-17 antibody. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria set forth in Ex parte Forman (230 USPQ 546 (Bd. Pat. App. & Int. 1986), and reiterated in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)), which include (1) the quantity of experimentation necessary, (2) the amount of 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, is the basis for determining undue extermination.
Claims 36-49 encompass a method of inducing regeneration of tendon tissue or promoting tendon repair in a patient having tendinopathy, said method comprising administering to said subject an effective amount of anti-human IL-17 antibody as defined in claim 36. This antibody has no binding function other than binding to an epitope comprising certain amino acids of the two mature human IL-17 protein chains making an IL-17 homodimer. It must, however, also have a KD for human IL-17 of about 100-200 pM and an in vivo half-life of about 4 weeks. Claim 48 provides more structural limitations of the antibody.
The specification teaches that the induction of tendinopathy significantly increased the MRI T2 inflammation signal, which triggered imbalance in gait and significantly increased the front-hind ratio of the footprint in an in vivo rat disease model (see Example 1). The specification teaches that the anti-IL-17 monoclonal antibody CJM112, which binds and neutralizes IL-17A, reversed the increased MRI T2 tendinopathy inflammation signal and also reversed the imbalance in gait (see page 48). Moreover, Figure 3 shows that the antagonistic IL-17A antibody BZNO35 (which binds and neutralizes IL-17A) inhibits IL-17A induced IL6 and CXCL1 mRNA in rat Achilles tenocytes. While there is no evidence these two antibodies bind the epitope set forth in claim 36, it does show that IL-17 neutralizing antibodies reduce tendinopathy inflammation or biological markers thereof. According to the specification, Clinical study CAIN457F2312 looked at treatment with 75mg, 150mg or 300mg secukinumab compared to placebo in the treatment of patients with psoriatic arthritis, including patients with enthesitis. The instant specification defines as “enthesitis” as “inflammation at tendon, ligament or joint capsule insertions.” (p. 49, second paragraph) The results of the study are reported (Eur. Medicines Agency, Cosentyx Assessment report, 2015) as showing that at 24 weeks of treatment, there was a significant difference in resolution of enthesitis in secukinumab pooled doses compared to placebo in those patients with enthesitis as baseline, and a greater difference at 24 weeks for the 150mg and 300mg secukinumab doses compared to placebo (p. 44, third paragraph, of Eur. Medicines Agency, Cosentyx, the proprietary name for secukinumab). This does not support a finding of tendon regeneration or tendon repair. Further, there is no teaching in the specification or prior art of an agonistic anti-IL-17 antibody reducing inflammation. The specification specifically (p. 3, third paragraph) states, “In human tenocytes, IL-17 regulates pro-inflammatory cytokines,” which supports the need for antagonism of IL-17 to reduce inflammation.
However, the specification does not teach that the administration of an anti-IL-17 antibody induces regeneration of tendon tissue or promotes tendon repair in a patient having tendinopathy. The relevant art teaches that IL-17A is an inflammatory mediator within the early tendinopathy processes as early tendinopathy shows increased IL-17A expression (see Millar et al., Scientific Reports, 6:27149, DOI: 10.1038/srep27149, 06/06/2016, cited on the IDS of 03/08/2023, especially abstract and page 5). Moreover, Mease et al, (Rheumatology Therapy, 04/2016; Vol. 3, , cited on the IDS of 03/08/2023, pages 5-29), teach that secukinumab, (which selectively binds to and neutralizes IL-17A, inhibiting its interaction with IL-17 receptors) provided rapid and clinically meaningful improvements in multiple facets of psoriatic arthritis (PsA), including joint symptoms and enthesitis (inflammation at tendon insertions; see pages 5, 7, and 10). However, neither the instant specification nor any art of record teaches that the administration of an anti-IL-17 antibody induces regeneration of tendon tissue or promotes tendon repair in a patient having tendinopathy. The relevant art teaches that secukinumab did not demonstrate a significant benefit vs placebo in the overall patient population with active overuse rotator cuff tendinopathy, (RC TP), (see Millar et al., Ann Rheum Dis, 2021, 80(1): pages 211- 212, cited on the IDS of 03/08/2023, POS0020; under conclusion). Yang el al. (Birth Defects Research Part C-Embryo Today; 2013; 99 (3), pages 203-222, cited on the IDS of 03/08/2023, see abstract) teaches that several challenges remain in restoring full tendon and ligament function following injury, including uncertainties over the optimal combination of these biological agents as well as how to best deliver tissue engineered elements to the injury site. Likewise, Voleti et al. (Ann. Rev. Biomed. Engineering, 14:47-71, 2012, cited on the IDS of 03/08/2023) teaches that the tendon is a compositionally complex tissue with a predominantly mechanical function and that structural, biological, and mechanical changes are initiated during the process of tendon healing (see abstract). Voleti et al. teaches that the complex cascade of events initiated by a tendon injury is regulated by numerous biological factors with interconnecting pathways (see page 8).
In the instant case, the specification fails to teach that the administration of an anti-IL-17 antibody induces regeneration of tendon tissue or promotes tendon repair. One skilled in the art would not be able to predict that administration of anti-IL-17 antibody would lead to the induction of regeneration of tendon tissue or promote tendon repair, given the complex cascade of events initiated by a tendon injury which is regulated by numerous biological factors with interconnecting pathways. Moreover, as set forth above, tendinopathy is a complex multi-faceted tendon pathology commonly associated with inflammation and IL- 17A is but only one of many other contributing biological factors, such as IL-6, TNF, IL- 21, (see Millar et al., Nat. Rev. Rheumatology, 13:110-122, Feb. 2017, page 116, cited on the IDS of 3/08/2025). Therefore, inhibiting only IL-17 would not be expected to induce regeneration of tendon tissue or promote tendon repair. For these reasons and as discussed above, it would require undue experimentation to practice the method commensurate in scope with the claims. Therefore, only a method of reducing tendinopathy inflammation comprising administering an antibody that binds to and neutralizes IL-17A, is enabled.
Claims 50-54 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 of reducing tendinopathy inflammation in a patient by administering secukinumab to the patient in a dose of about 150 mg or about 300 mg by subcutaneous (SC) injection at weeks 0, 1, 2, 3, 4 and then every four weeks thereafter, for a total treatment duration of at least three months, does not reasonably provide enablement for treatment of any other condition in the patient. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Independent claim 50 is drawn to a method of treating a patient having active overuse tendinopathy, comprising administering by sc injection about 150 mg or about 300 mg secukinumab at weeks 0, 1, 2, 3, and 4 and then every 4 weeks thereafter, for a total treatment duration of at least 3 months. Dependent claims 51-54 further describes the patient. There are two enablement issues with these claims. First, there is no limit as to what is being treated. Second, there is a scope of enablement for what would reasonably have been expected to be treatable by the claimed method.
As noted above, claim 50 is drawn to treating a patient who happens to have active overuse tendinopathy. There is no requirement that the method treats said tendinopathy. It may be directed at treatment of psoriasis (p. 3, fourth paragraph, of the specification). That is, the treatment is of the patient not the disease or condition that patient has. Aside from approved treatment of plaque psoriasis, psoriatic arthritis and ankylosing spondylitis with secukinumab (p. 3, fourth paragraph, of the specification), the claims are enabled for reduction of tendinopathy inflammation as discussed below.
The specification teaches that the induction of tendinopathy significantly increased the MRI T2 inflammation signal, which triggered imbalance in gait and significantly increased the front-hind ratio of the footprint in an in vivo rat disease model (see Example 1). The specification teaches that the anti-IL-17 monoclonal antibody CJM112, which binds and neutralizes IL-17A, reversed the increased MRI T2 tendinopathy inflammation signal and also reversed the imbalance in gait (see page 48). Moreover, Figure 3 shows that the antagonistic IL-17A antibody BZNO35 (which binds and neutralizes IL-17A) inhibits IL-17A induced IL6 and CXCL1 mRNA in rat Achilles tenocytes. While there is no evidence these two antibodies bind the epitope as secukinumab, it does show that IL-17 neutralizing antibodies reduce tendinopathy inflammation or biological markers thereof. As discussed in the specification, clinical study CAIN457F2312 looked at treatment with 75mg, 150mg or 300mg secukinumab compared to placebo in the treatment of patients with psoriatic arthritis, including patients with enthesitis. The instant specification defines “enthesitis” as “inflammation at tendon, ligament or joint capsule insertions.” (p. 49, second paragraph) The results of the study are reported (Eur. Medicines Agency, Cosentyx Assessment report, 2015) as showing that at 24 weeks of treatment, there was a significant difference in resolution of enthesitis in secukinumab pooled doses compared to placebo in those patients with enthesitis as baseline, and a greater difference at 24 weeks for the 150mg and 300mg secukinumab doses compared to placebo (p. 44, third paragraph, of Eur. Medicines Agency, Cosentyx, the proprietary name for secukinumab). These results are not fully supported by the results of Baraliakos et al. (Arthritis Res. Ther. 24: 111, 2022), which reports the findings of a phase 3 clinical trial (NCT02771210) using MRI to evaluate heel enthesitis in patients with spondyloarthritis treated with secukinumab. There was a positive trend at 24 weeks for total inflammation and total structural damage scores for secukinumab treated patients compared to placebo, but there was no statistically significant difference (p. 9/11, col. 2, first paragraph).
Further, while the specification supports reduction of tendinopathy inflammation and apparently subsequent improvement in gait imbalance in rats by administration of secukinumab, it does not support regeneration of tendon tissue or promotion of tendon repair in a patient having active overuse tendinopathy. The relevant art teaches that IL-17A is an inflammatory mediator within the early tendinopathy processes as early tendinopathy shows increased IL-17A expression (see Millar et al., Scientific Reports, 6:27149, DOI: 10.1038/srep27149, 06/06/2016, cited on the IDS of 03/08/2023, especially abstract and page 5). Moreover, Mease et al, (Rheumatology Therapy, 04/2016; Vol. 3, , cited on the IDS of 03/08/2023, pages 5-29), teach that secukinumab (which selectively binds to and neutralizes IL-17A, inhibiting its interaction with IL-17 receptors) provided rapid and clinically meaningful improvements in multiple facets of psoriatic arthritis (PsA), including joint symptoms and enthesitis (inflammation at tendon insertions; see pages 5, 7, and 10). However, neither the instant specification nor any art of record teaches that the administration of an anti-IL-17 antibody induces regeneration of tendon tissue or promotes tendon repair in a patient having tendinopathy. The relevant art teaches that secukinumab did not demonstrate a significant benefit vs placebo in the overall patient population with active overuse rotator cuff tendinopathy (RC TP; see Millar et al., Ann Rheum Dis, 2021, 80(1): pages 211- 212, cited on the IDS of 03/08/2023, POS0020; under conclusion). Yang el al. (Birth Defects Research Part C-Embryo Today; 2013; 99 (3), pages 203-222, cited on the IDS of 03/08/2023, see abstract) teaches that several challenges remain in restoring full tendon and ligament function following injury, including uncertainties over the optimal combination of these biological agents as well as how to best deliver tissue engineered elements to the injury site. Likewise, Voleti et al. (Ann. Rev. Biomed. Engineering, 14:47-71, 2012, cited on the IDS of 03/08/2023) teaches that the tendon is a compositionally complex tissue with a predominantly mechanical function and that structural, biological, and mechanical changes initiated during the process of tendon healing are complex (see abstract). Voleti et al. teaches that the complex cascade of events initiated by a tendon injury is regulated by numerous biological factors with interconnecting pathways (see page 8).
For the reasons discussed above and including the breadth of conditions/disease to be treated, the lack of guidance or direction for treating other than tendinopathy inflammation, plaque psoriasis, psoriatic arthritis and ankylosing spondylitis with secukinumab, the lack of support in the specification or prior art for treatment of other than those conditions/diseases, the complexity of tendon structure and function, and the lack of predictability for an anti-IL17 antagonistic antibody functioning other than in the reduction of inflammation, particularly of the tendon, it would require undue experimentation to practice the invention commensurate in scope with the claims.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
ClinicalTrials.gov study NCT02771210 (version 3, https://clinicaltrials.gov/study/NCT02771210?limit=100&sort=@relevance&intr=AIN457&page=1&rank=83&tab=history&a=3#version-content-panel, 07/05/2016, Official Title) teaches “A Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy in the Treatment of Enthesitis at the Achilles Tendon up to 1 Year in Adult Patients With Active Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA) (ACHILLES)”. It is also known as study CAIN457F3301 (Unique Protocol ID). The study was designed to demonstrate efficacy of treatment on inflammation determined by magnetic resonance imaging (MRI, Brief Summary). Results were posted 01/27/2021 (https://clinicaltrials.gov/study/NCT02771210?limit=100&sort=@relevance&intr=AIN457&page=1&rank=83&tab=results&a=3, [retrieved 08/12/2025], attached). One can see that while there were trends as discussed by Baraliakos et al. (Arthritis Res. Ther. 24: 111, 2022, supra), which reviewed the study results, there was no statistically significant effect of the secukinumab treatment on tendon inflammation.
ClinicalTrials.gov Study NCT03344640, Posted results of the completed trial (https://clinicaltrials.gov/study/NCT03344640?limit=100&sort=@relevance&intr=AIN457&page=1&rank=17&tab=results>, 10/08/2021). The study is entitled “Study of Efficacy, Safety and Tolerability of AIN457 in Patients with Active Overuse Tendinopathy”. The trial was first submitted after the effective filing date of the instant application. For some methods of assessment, it shows a suggestion that antibody AIN457 (secukinumab) may be beneficial for this tendinopathy but none of the results are statistically significant.
Conclusion
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
August 12, 2025