DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
The amendments filed 06/15/2026 have been entered. Claim 2 is cancelled. Claims 1, 3-5, 7, and 15-21 are amended.
Claims 1 and 3-21 are rejected.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 06/15/2026 and 06/25/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendments
Withdrawn Objections/Rejections
Claim Objections
The previous claim objections regarding claims 16-21 for being a multiple dependent claim depending on another multiple dependent claim is withdrawn in response to the amendment making the claims only dependent on claim 1.
The previous claim objections regarding claim 4 for the typographical error is withdrawn in response to the amendment deleting the second recitation of “wherein”.
Claim Rejections - 35 USC § 112(a)
The previous 35 USC § 112(a) rejection regarding claim 2 is withdrawn in response to the cancellation of claim 2.
Maintained Rejections
Applicant’s arguments, see page 7, filed 06/15/2026, with respect to the rejection(s) of claim(s) 1-15 under 35 USC § 103 and Double Patenting have been fully considered and are persuasive in view of the amendments to claim 1. However, upon further consideration, a new ground(s) of rejection is made in view of additional teachings from the references related to Applicant’s amendments.
Furthermore, in response to the amendments making the claims 16-21 dependent only on claim 1 and not an improper multiple dependent claim, as previously explained in the withdrawn claim objections section of this office action, claims 16-21 are entered into examination.
The rejections have been updated accordingly.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-19 are rejected under 35 U.S.C. 103 as being unpatentable over WO ‘234 (WO2018220234A1; published 12/06/2018) in view of Balchen et al (Balchen et al, Study design of a phase I, placebo-controlled, First-in-human trial to assess safety and tolerability, immunogenicity, and pharmacokinetics and pharmacodynamics of single ascending doses of the anti-ADAMTS-5 Nanobody®, M6495, in healthy male subjects; published 04/2018).
Regarding claim 1, WO ‘234 teaches a method of treating osteoarthritis in a subject in need thereof comprising administering ADAMTS5 inhibiting polypeptide to a human subject (Abstract and page 12 line 13 – page 13 line 5). WO ‘234 teaches that the ADAMTS5 inhibiting polypeptide was able to sustain inhibition of aggrecanase, which is a degrader of a component of cartilage, after one administration for at least 4 weeks (p. 99, lines 5-12; Figure 10). WO ‘234 teaches that the ADAMTS5 inhibiting polypeptide has stability at 37°C in synovial fluid for at least 7 days, such as 14 days, 21 days, 1 month, 2 months, or even 3 months (p. 11, lines 26-28). WO ‘ 234 teaches this stability enables less frequent dosage regimen. WO ‘ 234 teaches that the treatment regimen will be followed for as long as the desired therapeutic effect is to be maintained, as can be determined by the clinician (p. 73, lines 4-6). WO ‘ 234 teaches that the regimen could be long-term, lasting weeks, months, or years (p. 71, lines 18-21).
WO ‘234 does not explicitly teach administering 75 - 300 mg of an ADAMTS5 inhibiting polypeptide.
However, WO ‘234 does teach that the dosage regimen should be determined by the physician and clinical factors, as it depends on many factors, including patient’s weight, route of administration, and other factors (page 70, lines 17-21).
Furthermore, Balchen et al teaches a registered clinical study method of treating osteoarthritis in humans comprising of administering an ADAMTS5 inhibiting polypeptide (called M6495) in doses increasing from 1 mg to 5 mg to 20 mg to 75 mg to 150 mg, and optionally to 300 mg (Methods and Figure 1). Balchen et al teaches that the lowest dose, 1 mg, is due to predicted median PD effect at ED10 (i.e. 10% of maximum effects achieved) from monkey data, and that the highest dose, 300 mg, is given if 90% of maximum effects (i.e. ED90) has not been achieved at 150 mg (Methods).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to select dosages within the dosage range disclosed by Balchen et al, especially the higher doses at and around 150 mg, as it is expected that most effects will be achieved by 150 mg, but in rare cases, 300 mg may be required. It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the administration regimen would continue long-term for as long as the therapeutic effect is desired, which could include more than one dose, as taught by WO ‘234. Especially in light of the stability of the ADAMTS5 inhibiting polypeptide and its ability to maintain inhibition of aggrecanase even after one month, it would have been obvious to one skilled in the art, before the effective filing date of the instant application, that administration could be done once monthly to maintain the therapeutic effect.
One skilled in the art, before the effective filing date of the instant application, would be motivated to choose at least 150 mg as the dose, as it is the dose predicted to give at least 90% of maximum effects. One skilled in the art, before the effective filing date of the instant application, would be motivated to maintain the therapeutic effects by administering multiple doses and do at less frequent dosing than the weekly dosing used in some of the example treatments, such as monthly, taking advantage of the stability of the ADAMTS5 inhibiting polypeptide in synovial fluid and sustained therapeutic effect.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success as this is the dose used for another anti-ADAMTS-5 nanobody in a human clinical trial of the same disease model. Therefore, the dose must have been stringently vetted for reasonable safety and potential therapeutic effects. Furthermore, the administration regimen is based on the stability of the molecule in the site of action (synovial fluid) and on the stability of the therapeutic effect in a representative animal disease model.
Claims 3, 7, 13, and 15-21 depend on claim 1. Claims 4-5 further depend on claim 3. Claim 6 further depends on claim 5. Claims 8, 10, and 12 further depend on claim 7. Claim 9 further depend on claim 8. Claim 11 further depend on claim 10. Claim 14 further depend on claim 13. The teachings of the reference(s) for the parent claim(s) are incorporated in entirety for their dependent claims and further discussed below, as is relevant to each claim.
Regarding claims 2-4, WO ‘234 further teaches a method wherein the ADAMTS5 inhibiting polypeptide comprises at least one immunoglobulin single variable domain (ISVD) comprising 3 complementarity determining regions (CDR), wherein the complementary determining regions are CDRl to CDR3, in which CDR1 is instant SEQ ID NO: 21, CDR2 is instant SEQ ID NO: 37, and CDR3 is instant SEQ ID NO: 55, which have a 100% amino acid sequence match to WO ‘234 CDR1 SEQ ID NO: 21, WO ‘234 CDR2 SEQ ID NO: 37, and WO ‘234 CDR3 SEQ ID NO: 55, respectively, in the anti-ADAMTS5 nanobody referred to as 02F03 (or 2F03 or 2F3) and also identified with nanobody ID number 2 (Table A-2, page 109).
WO ‘234 further teaches the exact polypeptide comprising of CDR1-3 in which CDR1 is instant/WO ‘234 SEQ ID NO: 21, CDR2 is instant/WO ‘234 SEQ ID NO: 37, and CDR3 is instant/WO ‘234 SEQ ID NO: 55 (claim 12). WO ‘234 further teaches that this nanobody (2F03) comprising of this combination of CDR1-3 is one of only three nanobodies disclosed that has an IC50 (i.e. potency) similar to a full-length monoclonal anti-ADAMTS5 antibody called mAb 12F4 used as a positive control polypeptide in their disclosed experiments (Table 5.1 on page 84, which demonstrated both structural disease modification and alleviation of pain-related behavior (page 4, lines 13-14). Further, nanobody 2F03 has the closest IC50 to mAb 12F4 (Table 5.1, page 84).
Regarding claims 5-6, WO ‘234 further teaches wherein the ISVD is amino acids 1-124 of instant SEQ ID NO: 129, as seen in the construct defined by WO ‘234 SEQ ID NO: 129 (page 108 of Table A-1) which discloses a sequence optimized version of nanobody 2F3, called nanobody 2F3*, which is the amino acids 1-124 of instant SEQ ID NO: 129, fused to a (GGGS)n linker, fused to another polypeptide.
Regarding claims 7-14, WO ‘234 further teaches wherein the ADAMTS5 inhibiting polypeptide comprises of two ISVDS, wherein the first ISVD specifically binds ADAMTS5 and is amino acids 1-124 of instant SEQ ID NO: 129 and the second ISVD binds serum albumin and is instant SEQ ID NO: 138 (page 108 of Table A-1, see construct 2F3*-A1b which is WO ‘234 SEQ ID NO: 129). Essentially, claim 14 is one embodiment of broader claims 7-13, and WO ‘234 teaches this exact embodiment of claim 14. Finally, this exact embodiment was singled out to be tested as construct 581 or “C011400581” in Figures 4-14, showing, for example, sustained inhibition of ADAMTS5/aggrecanase activity (page 90, lines 5-11 and Figure 10).
Regarding claim 15, WO ‘234 further teaches their example methods and experiments were done with assessing knee joints/cartilage as a model of osteoarthritis, but inherently, specifically knee osteoarthritis (e.g. Section 5.2 page 85 and Example 9 for bovine knee joints; Example 8 for human knee joints; Examples 11 for monkey knee joints).
Regarding claims 16 and 17, as previously recited, Balchen et al teaches a registered clinical study method of treating osteoarthritis in humans comprising of administering an ADAMTS5 inhibiting polypeptide (called M6495) in doses increasing from 1 mg to 5 mg to 20 mg to 75 mg to 150 mg, and optionally to 300 mg (Methods and Figure 1). Balchen et al teaches that the lowest dose, 1 mg, is due to predicted median PD effect at ED10 (i.e. 10% of maximum effects achieved) from monkey data, and that the highest dose, 300 mg, is given if 90% of maximum effects (i.e. ED90) has not been achieved at 150 mg (Methods).
Regarding claim 18, the teachings, motivation, and expectation of success for administration once a month was explained for claim 1.
Regarding claim 19, as previously recited, WO ‘234 teaches the ADAMTS5 inhibiting polypeptide decrease formation of ARGS fragments (Figure 10 and p. 99, lines 5-12 ).
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over WO ‘234 (published 12/06/2018) in view of Balchen et al (published 04/2018), as applied to claim 1 above, and further in view of Zhang et al (Zhang et al, Current research on pharmacologic and regenerative therapies for osteoarthritis, Bone Research; published 03/01/2016).
The teachings of the references for the parent claim are incorporated in their entirety for the dependent claims and discussed further below, as relevant.
Regarding claims 20-21, WO’234 teaches symptomatic benefit via gait analysis and decrease in joint diameter in rat OA models from ADAMTS5 inhibiting polypeptide administration (p. 100, Example 12; Figure 12)
WO ‘234 and Balchen et al do not explicitly teach administration of the ADAMTS5 inhibiting polypeptide decreases pain in OA-affected joints as determined by KOOS score or WOMAC score, nor that it maintains the structure of OA-affected joints as determined by automated segmentation in MRI.
However, Zhang et al teaches that during osteoarthritis progression, OA chondrocytes produce ADAMTS-5, which targets aggrecan in the cartilage matrix. These degradative enzymes further exacerbate the breakdown of articular cartilage, contributing to painful cartilage destruction (p. 2, col. 1, para. 2 – col. 2, para. 1). Zhang et al further teaches through other OA-therapeutic studies that the KOOS score (e.g. p. 8, section: Cell-based scaffolds and Cell-free scaffolds) and WOMAC score (e.g. p. 6, section: Platelet-rich plasma, section: Human serum albumin; and p. 9, section: Gene therapy) are used to measure pain in osteoarthritis affected joints and the scores improved with OA treatment, usually accompanied by improved cartilage structure visualized by MRI (e.g. p. 7, col. 2, para. 2; p. 8, section: Cell-based scaffolds). Zhang et al acknowledges ADAMTS-5 as one of the main matrix-degrading enzymes that is key to development of OA (p. 9 col. 2, para. 2) and recite ADAMTS-5 inhibitor as a potential OA therapeutic (p. 5, Table 2).
Zhang et al does not explicitly teach the joint structure on the MRI images is determined by automated segmentation. However, as automated segmentation is trained to detect the joint based on the ground truth, often based on manual segmentation, it would be expected that if the joint structure is maintained, automatic segmentation, or any segmentation, could be used to determine this.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that if the ADAMTS5 inhibiting polypeptides are preventing cartilage degeneration and improving symptoms (i.e. pain), as taught by WO ‘234, then the MRI, KOOS score, and WOMAC score would reflect and reveal these structural and symptomatic truths.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use quantitative (KOOS score and WOMAC score) and qualitative (MRI) metrics commonly used in OA research to determine therapeutic effects to characterize the ADAMTS5 inhibiting polypeptide’s ability to maintain cartilage structure and alleviate symptoms.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because these scores and the MRI are means to confirm the ground truth that the ADAMTS5 inhibiting polypeptide prevents the degradation of cartilage and therefore alleviates the pain associated with OA progression. Since the references teaches ADAMTS5 provides these benefits, it follows that pain scores and imaging would reflect these benefits.
Double Patenting
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). The applicant should amend or cancel claims such that the reference and the instant application no longer contain claims directed to the same invention.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Patent No. US12209136B2
Instant claims 1, 3-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. US12209136B2 in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and further in view of Balchen et al (Balchen et al, Study design of a phase I, placebo-controlled, First-in-human trial to assess safety and tolerability, immunogenicity, and pharmacokinetics and pharmacodynamics of single ascending doses of the anti-ADAMTS-5 Nanobody®, M6495, in healthy male subjects; published 04/2018).
The instant claims are directed towards a method of treating osteoarthritis in a human subject in need thereof comprising administering 75-300 mg of an ADAMTS5 inhibiting polypeptide. Dependent claims further define the ADAMTS5 inhibiting polypeptide as comprising of specific sequences of ISVD that bind to ADAMTS5 and, in some embodiments, comprising of specific sequences of another ISVD that bind to serum albumin.
Patent ‘136 claims are directed towards a method of treating osteoarthritis in a human subject in need thereof comprising administering an ADAMTS5 inhibiting polypeptide. Dependent claims further define the ADAMTS5 inhibiting polypeptide as comprising of specific sequences of ISVD that bind to ADAMTS5 and comprising of specific sequences of another ISVD that bind to serum albumin. Patent ‘136 distinctly claim embodiments which match the embodiments of sequences or read on the genus of embodiments instantly claimed for each ISVD. For ease of comparison, it should be noted that clone 577 is the same as instant construct 581, by definition and sequence defined in the instant specification (Table A-1). Patent ‘136 claims arrive at all the ADAMTS5 inhibiting polypeptides instantly claimed and most of the limitations of the instant claims.
Patent ‘136 claims do not explicitly teach administering 75 - 300 mg of the ADAMTS5 inhibiting polypeptide nor the specific dosing regimen.
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with these limitations and the limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Claims 20 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. US12209136B2 in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and Balchen et al (Balchen et al, Study design of a phase I, placebo-controlled, First-in-human trial to assess safety and tolerability, immunogenicity, and pharmacokinetics and pharmacodynamics of single ascending doses of the anti-ADAMTS-5 Nanobody®, M6495, in healthy male subjects; published 04/2018).
as applied to claim 1 above, and further in view of Zhang et al (Zhang et al, Current research on pharmacologic and regenerative therapies for osteoarthritis, Bone Research; published 03/01/2016).
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Application No. 18983096
Instant claims 1 and 3-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18983096 (claims filed 05/02/2025) in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and further in view of Balchen et al (Balchen et al, Study design of a phase I, placebo-controlled, First-in-human trial to assess safety and tolerability, immunogenicity, and pharmacokinetics and pharmacodynamics of single ascending doses of the anti-ADAMTS-5 Nanobody®, M6495, in healthy male subjects; published 04/2018). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed towards a method of treating osteoarthritis in a human subject in need thereof comprising administering 75-300 mg of an ADAMTS5 inhibiting polypeptide. Dependent claims further define the ADAMTS5 inhibiting polypeptide as comprising of specific sequences of ISVD that bind to ADAMTS5 and, in some embodiments, comprising of specific sequences of another ISVD that bind to serum albumin.
App ‘096 claims are directed towards a method of treating a disease in a human subject in need thereof comprising administering an ADAMTS5 inhibiting polypeptide. Dependent claims further define the disease to be osteoarthritis, the ADAMTS5 inhibiting polypeptide as comprising of specific sequences of ISVD that bind to ADAMTS5 and comprising of specific sequences of another ISVD that bind to serum albumin. App ‘096 distinctly claim embodiments which match the embodiments of sequences or read on the genus of embodiments instantly claimed for each ISVD. App ‘096 claims arrive at all the ADAMTS5 inhibiting polypeptides instantly claimed and most of the limitations of the instant claims.
App ‘096 claims do not explicitly teach administering 75 - 300 mg of the ADAMTS5 inhibiting polypeptide nor the dosing regimen.
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with these limitations and the limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Claims 20 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18983096 (claims filed 05/02/2025) in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and further in view of Balchen et al (published 04/2018), as applied to claim 1 above, and further in view of Zhang et al (Zhang et al, Current research on pharmacologic and regenerative therapies for osteoarthritis, Bone Research; published 03/01/2016).
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Application No. 18482187
Instant claims 1 and 3-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 8, and 30 of copending Application No. 18482187 (claims filed 02/22/2024) in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and further in view of Balchen et al (Balchen et al, Study design of a phase I, placebo-controlled, First-in-human trial to assess safety and tolerability, immunogenicity, and pharmacokinetics and pharmacodynamics of single ascending doses of the anti-ADAMTS-5 Nanobody®, M6495, in healthy male subjects; published 04/2018). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed towards a method of treating osteoarthritis in a human subject in need thereof comprising administering 75-300 mg of an ADAMTS5 inhibiting polypeptide. Dependent claims further define the ADAMTS5 inhibiting polypeptide as comprising of specific sequences of ISVD that bind to ADAMTS5.
App ‘187 claims are directed towards a method of preventing a symptom or treating a disease/disorder, such as osteoarthritis, in a subject in need thereof comprising administering a polypeptide disclosed to comprise of at least one ISVD that binds to ADAMTS. Dependent claims further define the ADAMTS as ADAMTS5, and further define specific sequences of the ISVD binding ADAMTS5. App ‘187 distinctly claim embodiments which match the embodiments of sequences or read on the genus of embodiments instantly claimed for each ISVD binding ADAMTS5. For ease of comparison, it should be noted that instant CDR1-3 defined by SEQ ID NO: 21, 37, and 55, respectively, have a 100% amino acid sequence match, respectively, to App ‘187 CDR1-3, defined by SEQ ID NO: 14, 16, and 18, respectively.
App ‘187 claims do not explicitly teach administering 75 - 300 mg of the ADAMTS5 inhibiting polypeptide nor the dosing regimen. App ‘187 claims do not explicitly teach the ADAMTS5 inhibiting polypeptide comprising of a second ISVD that binds serum albumin.
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with these limitations and the limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Instant claims 20 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 8, and 30 of copending Application No. 18482187 (claims filed 02/22/2024) in view of WO ‘234 (WO2018220234A1; published 12/06/2018) and Balchen et al (published 04/2018), as applied to claim 1 above, and further in view of Zhang et al (Zhang et al, Current research on pharmacologic and regenerative therapies for osteoarthritis, Bone Research; published 03/01/2016). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The teachings of the prior art references regarding going from a baseline method of treating OA with ADAMTS5 inhibiting polypeptide with limitations of the dependent claims, the motivation to combine the teachings of the references, and the reasonable expectation of success for combining is provided previously in the updated 35 USC 103 rejections.
Response to Arguments
Objections to the Claims
No arguments were presented. The objections were withdrawn in response to Applicant’s amendments, as discussed in the Withdrawn Objections/Rejections section of this office action.
Claim Rejections - 35 USC § 112(a)
No arguments were presented. The rejections were withdrawn in response to Applicant’s amendments, as discussed in the Withdrawn Objections/Rejections section of this office action.
Claim Rejections - 35 USC § 103
Applicant amends the claims to add further dosing regimen limitations and argues that the previously presented teachings by the prior art references do not teach these limitations.
Applicant’s arguments, see page 7, filed 06/15/2026, with respect to the rejection(s) of claim(s) 1-15 under 35 USC § 103 have been fully considered and are persuasive, taken with the amendments to the claims. However, upon further consideration, a new ground(s) of rejection is made in view of additional teachings of the prior art that read on the amended claims.
The previous rejection did not discuss the added limitations. However, the prior art references teach the added limitations, as discussed in the updated 35 USC § 103 rejections. Therefore, the rejections are maintained and updated to reflect the amended claims.
Double Patenting
Applicant amends the claims to add further dosing regimen limitations and argues that the previously presented teachings by the prior art references and the double patenting references do not teach these limitations, as discussed in the argument for the 35 USC § 103 rejection.
Applicant’s arguments, see page 8, filed 06/15/2026, with respect to the rejection(s) of claim(s) 1-15 under Double Patenting have been fully considered and are persuasive, taken with the amendments to the claims. However, upon further consideration, a new ground(s) of rejection is made in view of additional teachings of the prior art that read on the amended claims.
As discussed in the updated 35 USC § 103 rejections and the response to arguments for the 35 USC § 103 rejections, the prior art references teach the additional limitations in the amended claims. Therefore, the rejections are maintained and updated to reflect the amended claims.
Conclusion
All claims are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BONIRATH CHHAY whose telephone number is (571)272-0682. The examiner can normally be reached Mon-Thu 8AM-5PM EST.
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/BONIRATH CHHAY/Examiner, Art Unit 1645 Thursday, July 16, 2026
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 27, 2026
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