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 .
Summary
Receipt of Applicant’s Amendment/Remarks filed on 12/16/2025 is acknowledged. Claims 1-17 and 20-32 are pending. Claim 1 is amended. Claims 1-17 and 26-32 are pending and under examination in this application.
Election/Restrictions
Applicant elects Group I without traverse, claims 1-17 and 26-32 for a method of treating stroke.
Group II, claims 20-25 are cancelled and withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The election is made FINAL.
Maintained Rejections
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.
Claim(s) 1-17 and 26-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al. (US 2013/02955012 A1) (hereinafter the reference is referred as Ingber) in view of Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels (hereinafter the reference is referred as Korin).
Ingber teaches methods and compositions directed to a large number of therapeutic applications, for example, stroke, acute coronary syndrome, myocardial infarction, atherosclerosis …, all share vascular narrowing at the disease site as a common feature, and thus, the shear-activated drug delivery system can be useful for all of these diseases because the design of the living vasculature tends to restrain wall shear stress to a narrow and nearly constant range to minimize work under physiological conditions (¶ 0471) comprising an aggregate of plurality of nanoparticles, wherein the aggregate disaggregates under shear stress (¶ 0007). Moreover, Ingber discloses The shear-activated delivery technology involves fabrication of microaggregates of NPs that remain intact under fluid shear stress levels experienced in normal Small and large vessels, but disaggregate and deploy their active NP components in diseased regions characterized by high shear (>100 dyne/cm), much like living platelets do. In contrast to microscale aggregates, the dispersed NPs rapidly adhere to the surface of the adjacent vessel wall due to smaller drag forces, and this can be further enhanced by surface coatings on the NPs (¶ 0482).
Regarding claims 1-7, and 10, Ingber teaches an aggregate for therapeutic use, and more especially for treating stroke, comprising a plurality of nanoparticles, wherein the aggregate disaggregates above a predetermined shear stress when exposed to said predetermined shear stress, and the aggregate further comprises an active agent that can be nimodipine or nitroglycerin. The nanoparticles are made of PLGA and the aggregate dissolve when the shear stress is above 100 dynes/cm2 (claims 1, 2, 4, 7, 51, 51, and ¶ 0014, ¶ 0025, ¶ 0037, ¶ 0122, ¶ 0171, ¶ 0278, examples 1-3), and comprises pharmaceutically acceptable excipients and carriers (¶ 0197). It is noted that the claim preamble recites “a method of treating stroke by increasing blood supply to the brain via collateral vessels” and penumbra would necessarily be inclusive, this feature is believed to be an inherent action of the injection of the shear activate nanoparticles, thus any document disclosing SA-NTs similar to the ones claimed in the present application will have the same mode of action and will increase the blood supply to the brain as described in present claim 1.
Regarding claim 8, Ingber teaches in some embodiments, one or more compounds can be associated with the aggregate encapsulated bound to the surface, or otherwise associated with the aggregate or a nanoparticle constituent of the aggregate (¶ 0036), and the compound can be covalently associated with the NPs in the aggregate (¶ 0037) and in other aspects, the compound is absorbed on the surface of the NP ( ¶ 0038).
Regarding claim 9, Ingber teaches under elevated shear stress, the rate of release of an encapsulated compound from the microcapsule is at least 10% to 90 %, at least 1-fold to at least 100-fold or higher, relative to release under non-elevated shear stress (i.e. normal blood vessel shear stress) (¶ 0099- ¶ 0100).
Regarding claims 11-14 and 26-30, Ingber teaches intravenous (¶ 0195, ¶ 0201), bolus injection (¶ 0470), continuous intravenous infusion administration (¶ 0202, ¶0313); ischemic sudden death, transient ischemic attach (ischemic stroke) (¶ 0186, ¶ 0187);
Regarding claims 15 and 30, as noted above, because Ingber teaches SA-NTs and method of treatment to ischemic stroke, with PLGA NPs and the aggregate dissolve when the shear stress is above 100 dynes/cm2, it would have been obvious to one of ordinary skill in the art to reasonably to expect increase blood flow to penumbra as well. Therefore, the limitation and structural feature is taught.
Korin teaches biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism to deliver drugs to the obstructed blood vessels, wherein microscale aggregates of NPs were fabricated to break up into nanoscale component when exposed to abnormally high shear stress (abstract). Moreover, Korin discloses shear-activated nanotherapeutics (SA-NTs) are similar in size to natural platelets (1 to 5 µm in diameter) (page 738, mid column, 2nd ¶), the design of a thrombolytic delivery system that targets drugs selectively to sites of flow obstruction and concentrates the active drug in areas that affect ischemic stroke, coronary infarction, and pulmonary embolism (page 738, left column, 1st ¶).
Regarding claims 16 and 31, Korin teaches SA-NTs coupled to a thrombolytic agent (tissue plasminogen activator - tPA) which has high affinity for fibrin, and thus, they were efficiently delivered to the fibrin clots (fig. S1) (page 741, right column - ¶ 2).
Regarding claims 17 and 32, Korin teaches the shear-activated drug targeting nanotechnology allow the immediate administration of clot-busting drugs to patients suspected to have life-threatening clot in the brain, lung, or other vital organs by emergency technicians or other caregivers, even before the patient has reached a hospital setting (page 741, Fig. 4. and right column – last ¶).
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 incorporate the active vasodilatory agent of Ingber into Korin’s SA-NTs with the biocompatible, biodegradable PLGA composition in order to develop effective drug delivery system to target treating stroke by increasing blood supply to the brain via collateral vessels as taught by Ingber in view of Korin. One would have been motivated to do so because the combined teaching of Ingber in view of Korin discloses methods for treating ischemic stroke, coronary infarction, and pulmonary embolism. One of ordinary skill in the art would have been motivated to do this because both of the references are drawn to methods for using shear-activated nanotherapeutics (SA-NTs) thrombolytic delivery system that target drugs selectively to sites of blood flow obstruction in regions of the brain.
One of ordinary skill in the art would have found it obvious to apply the different methods of development, for example to include the biocompatible, biodegradable PLGA, desired diluents and carriers to improve the drug delivery system and use as taught by Ingber in view of Korin. From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered but they are not persuasive. Applicant amended claim 1 to now require in the method of treating stroke by increasing blood supply to brain and that the aggregate is configured to disaggregate at a predetermined shear stress of greater than 30 dynes/cm2 to correspond with regions of the non-obstructed collateral vessels of the ischaemic penumbra following the onset of a stroke.
Both Ingber in view of Korin teaches methods for using shear-activated nanotherapeutics (SA-NTs) and disaggregation of NPs greater than 30 dynes/cm2 and the NPs are made of PLGA and the aggregate dissolve when the shear stress is above 100 dynes/cm2 (Ingber, claims 1-7, examples 1-3, ¶ 14, ¶ 25,¶ 122, ¶ 171) and Korin teaches SA-NP for drug targeting to obstructed blood vessels, wherein microscale aggregates of NPs were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. The art teaches the same composition administered in the same way to the same target location (to increase blow flow to the brain, Ingber ¶ 0460; Korin, entire ref). Claim 1 requires increasing blood supply to brain via “collateral vessels”, this feature is believed to naturally occur by the action of the injection of the SA-NPs, and any art that teaches this same composition in same subject matter of treatment in stroke will have the same mode of action and will increase blood supply to the brain and even in the real estate of penumbra.
Therefore, one of ordinary skill in the art would find the increase of blood supply to the collateral blood vessels and obvious effect after such an administration of the composition. There is no evidence showing criticality or unexpected results comparing the claimed invention with that of prior art.
Conclusion
No claims are 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 ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached at 571-272-0323. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615