Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Response to Amendment
Applicant’s amendments of the specification and the claims filed 13 March 2026 have been entered. Applicant’s remarks filed 13 March 2026 are acknowledged.
Claim 3 is cancelled. Claims 1-2 and 4-20 are pending and under examination.
Specification
The objections to the abstract and specification for informalities are withdrawn in response to Applicant’s amendments of the abstract and specification.
It is suggested to amend paragraph [0001] as the following:
[0001] This application is a divisional application of U.S. Patent Application No. 18/482,891, filed 10/8/2023, now US 12,419,903, which is a continuation-in-part of U.S. Patent Application No. 17/215,839, filed 3/29/2021, now US 11,780,871, which claims priority to U.S. Provisional Patent Application No. 63/005,136, filed 4/3/2020, each of which are incorporated by reference herein.
Claim Objections/Rejections Withdrawn
The objection to claim 1 for a typographical error is withdrawn in response to Applicant’s amendment of the claim.
The rejection of claims 1-2, 4-11 and 15-20 under 35 U.S.C. 102(a)(1), as being anticipated by Bertonis et al. (US 2018/0000737 A1, Pub. Date: Jan. 4, 2018), is withdrawn in response to Applicant’s amendment of independent claim 1 to require the composition comprising an anti-Stabilin-2 antibody.
The rejection of claims 12-13 under 35 U.S.C. 103, as being unpatentable over Bertonis et al. (US 2018/0000737 A1), is withdrawn in response to Applicant’s amendment of the claims as above.
Claim Rejections Maintained
Claim Rejections - 35 USC § 103
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.
Amended claims 1-2 and 4-20 are rejected under 35 U.S.C. 103 as being unpatentable over Bertonis et al. (US 2018/0000737 A1, Pub. Date: Jan. 4, 2018), in view of Hirose et al. (Proc. Nat’l. Acad. Sci. U.S.A., 2012, Vol. 109(11):4263-4268) (both references provided previously).
Ground of Rejection
Bertonis teaches a composition comprising aggregates, which comprise hyaluronan and/or chitosan, and a pharmaceutical agent [0003]. Bertonis teaches that the composition is in a dry form, which is suitable for storage, and may include a liquid carrier (e.g., water), which optionally include components such as salt(s) and additional pharmaceutical agent(s) [0003] [0004]. Bertonis teaches that the composition may be injected into the joint of a patient having joint distress, in order to achieve beneficial results such as pain alleviation and/or increased lubrication of the joint and/or inhibition of the processes that underlie certain forms of arthritis [0004]. Bertonis teaches that suitable hyaluronans include high molecular weights (HMW) hyaluronan of 1.0-4.0 mDa (1,000-4,000 kDa), and an exemplary hyaluronan is from Lifecore Biomedical, which has an average molecular weight of 1,350 KDa [0031]. Bertonis teaches that the primary components of the aggregates (chitosan and/or hyaluronan) are biocompatible and may be used in combination with platelet rich plasma (PRP) [0078]. Bertonis teaches that the composition may include both PRP and a steroidal or non-steroid agent as disclosed herein, and that combining PRP with NSAID may provide inhibition of cyclo-oxygenase (COX) enzymes, which are a major mediator for inflammation [0060]. As evidenced by Girish et al. (Life Sciences, 2007, Vol. 80(21):1921-1943) (reference provided previously), steroids (e.g., dexamethasone) and NSAIDs (e.g., indomethacin) are anti-inflammatory drugs that act as hyaluronidase inhibitors (p. 1932 Table 7). Bertonis teaches that the aggregates (i.e., hyaluronan) may be in the form of nanoparticles [0121]. Bertonis teaches that the aqueous carrier may be a hydrogel, and the aggregates may be dispersed in the hydrogel [0144].
Bertonis teaches as set forth above. Bertonis, however, does not teach wherein the composition comprises an anti-Stabilin-2 antibody (claim 1).
Hirose teaches that hyaluronic acid (HA) is rapidly cleared from the bloodstream, and the scavenger receptor Stabilin-2 (Stab2) is considered a major clearance receptor for HA (see Abstract). Hirose teaches that administration of an anti-Stablin-2 antibody elevated circulating hyaluronic acid levels by blocking the clearance of HA (ibid.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include an anti-Stabilin-2 antibody in the composition of Bertonis. One of ordinary skill in the art would have been motivated to do so, because Bertonis teaches a composition comprising hyaluronan and PRP for use in a pharmaceutical setting, and Hirose teaches that administration of an anti-Stablin-2 antibody can block the rapid clearance of HA. Therefore, the combined teachings provide a reasonable expectation of success in preparing a composition useful for treatment of a patient.
Regarding claims 6, 8 and 15, which recite that the composition is formulated as a dermal filler, or for implantation or topical administration, the composition taught and suggested by Bertonis and Hirose comprises the same components as recited in the instant claims, and therefore meets the claim limitations.
Regarding claims 12-13, which recite wherein the HMW-HA is present in an amount of between 100 mg and 1,000 mg per dose (claim 12), or wherein the PRP is present in an amount of between 1,000 mg and 5,000 mg per dose (claim 13), given that the level of skill in this art is very high, and that optimizing parameters such as the amount of an active agent/ingredient in a composition is routine, modifying the composition taught and suggested by Bertonis and Hirose to include the amount of HMW-HA or the amount of PRP in the claimed ranges would have been obvious to one of ordinary skill in the art at the time of the invention, with a reasonable expectation of success, absent evidence of unexpected results. As was found in In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Regarding claim 14, which recites wherein the anti-Stabilin-2 antibody is present in an amount of between 1 mg and 300 mg per dose, given that the level of skill in this art is very high, and that optimizing parameters such as the amount of an active agent/ingredient in a composition is routine, modifying the composition taught and suggested by Bertonis and Hirose to include the amount of the anti-Stablin-2 antibody in the claimed range would have been obvious to one of ordinary skill in the art at the time of the invention, with a reasonable expectation of success, absent evidence of unexpected results. As was found in In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Response to Applicant’s Arguments
Applicant argues that Hirose discusses anti-Stabilin-2 antibodies in the context of systemic hyaluronan clearance biology, Hirose, however, does not disclose a therapeutic composition comprising a combination of HMW-HA and anti-Stabilin-2 antibody with an optional additional ingredient PRP. Applicant argues that claim 1 requires that the composition be formulated for administration to treat an M1 macrophage-driven inflammatory condition, however, neither Bertonis nor Hirose discusses macrophage polarization, M1/M2 phenotypes, or treatment of M1 macrophage-driven inflammatory conditions. Applicant further argues that none of the cited prior art identify hyaluronan clearance via Stabilin-2 as a limiting factor in therapeutic efficacy, nor does it suggest that inhibiting HA clearance would improve clinical outcomes.
Applicant’s arguments have been fully considered but have not been found to be persuasive.
Bertonis teaches a composition comprising hyaluronan and PRP for use in a pharmaceutical setting (i.e., administering the composition to a patient), and Hirose teaches that administration of an anti-Stablin-2 antibody can block the rapid clearance of HA. A person skilled in the art would find it prima facie obvious to include an anti-Stabilin-2 antibody in a composition which comprises hyaluronan and PRP and is used for treating a patient. The skilled artisan would recognize that rapid clearance of hyaluronan (an active ingredient in Bertonis’ composition) would limit therapeutic efficacy, and on the other hand, inhibiting HA clearance would improve clinical outcomes.
With respect to Applicant’s argument that neither Bertonis nor Hirose discusses macrophage polarization, M1/M2 phenotypes, or treatment of M1 macrophage-driven inflammatory conditions, however, the instant claims are drawn to a composition, not a method of treatment. The cited prior art renders the claimed composition obvious. Any properties or activities are immaterial to the claimed composition. “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention” (see MPEP 2145 [R-2] and in re Wiseman, 596 F.2d 1019, 201 USPQ 658).
Double Patenting
Claims 1-2 and 4-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of U.S. Patent No. 12,419,903.
In the response received on 13 March 2026, Applicant requests that the nonstatutory double patenting rejection be held in abeyance pending resolution of the outstanding prior art rejection(s).
Conclusion
NO CLAIM IS ALLOWED.
THIS ACTION IS MADE FINAL. 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 Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674
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