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 .
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, claims 1-18 and 21-22, in the reply filed on 04/27/2026 is acknowledged.
Claim Status
The amendment of 04/27/2026 has been entered. Claims 1-22 are pending in this US patent application. Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/27/2026.
Claims 1-18 and 21-22 are currently under examination and were examined on their merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 14 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14 depends from claim 1 and recites “the CBPs.” However, claim 1 does not recite a CBP. As such, this claim lacks proper antecedent basis to its parent claim, which causes confusion because one of ordinary skill in the art would be unable to determine what element of claim 1 was intended to be limited by the recitation of “the CBPs” in claim 14. Therefore, claim 14 is indefinite and is rejected under 35 U.S.C. 112(b).
In the interest of compact prosecution, the Examiner has interpreted “the CBPs” in instant claim 14 to recite “the FBPs.”
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.
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.
Claims 1-16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al., Nanoscale 12: 21255-21270 (2020), in view of Xu et al., ACS Nano 13: 8577-8588 (2019), and Marder et al., Stroke 41(suppl. 1): S45-S49 (2010).
Sun teaches nanoparticles that target platelets and fibrin using corresponding peptide ligands that significantly enhance the clot-anchorage efficacy of nanoparticles while utilizing lower ligand densities as compared to nanoparticles that target platelets only or fibrin only (see entire document, including page 21257, left column, paragraph 1). The liposomal nanoparticles comprise DSPE-PEG-PBP, DSPE-PEG-FBP, DHPE-RhB, and cholesterol and were formed by dissolving these compounds in 1:1 chloroform:methanol and extruding the solution through polycarbonate membranes with a 200-nm pore size (page 21258, right column, paragraph 2; cf. claims 5-9 and 11). The sequence of the PBP was CGSSSGRGDSPA, which binds to platelet surface integrin αIIβ3, and the sequence of the FBP was cyclo-AC-Y(DGI)C(HPr)YGLCYIQGK-Am (page 21258, right column, paragraph 2; cf. claims 12 and 14). The DSPE-PEG-peptide conjugates were combined at ratios of 1:1, 80:20, 60:40, 40:60, and 20:80, while keeping the total DSPE-PEG-peptide content at 5% or 10% of total lipid (page 21259, left column, paragraph 1, to right column, paragraph 1; cf. claims 10 and 15). The nanoparticles bound to blood clots in the presence of shear stress (page 21260, left column, paragraph 1; cf. claim 2). The final nanoparticles had a diameter of approximately 160 nm (page 21261, right column, paragraph 2; cf. claim 5). The nanoparticles may be used for enhanced drug delivery in acute and chronic thrombosis (page 21267, right column, paragraph 1), particularly of fibrinolytic agents, for the minimization of systemic side effects (page 21256, left column, paragraph 2). The nanoparticles bound to arterial thrombi in mice (page 21265, left column, paragraph 2, to right column, paragraph 1; cf. claim 13).
However, Sun does not teach that the nanoparticles are thrombin-cleavable or that the drug in the nanoparticles is plasmin.
Xu teaches that fibrinolytic agents, such as tPA, may be shielded from the bloodstream in a nanoparticle and then released specifically at a thrombus by cleavage of a thrombin-cleavable peptide conjugated to a membrane lipid that forms part of the nanoparticle (see entire document, including page 8579, left column, paragraphs 3-4; page 8583, right column, paragraph 5, to page 8584, right column, paragraph 2; cf. claims 1, 4, and 16).
Marder teaches that plasmin possesses a different mode of activation than tPA and achieves thrombolytic efficacy without causing bleeding if shielded from α2-antiplasmin until it reaches the thrombus (see entire document, including page S45, left column, paragraph 2; cf. claims 1, 3, and 18). The safety margin for plasmin is significantly higher than that for tPA, which has the potential for hemorrhage at any dose that has a thrombolytic effect (page S45, right column, paragraph 1).
While Sun does not teach that the nanoparticles are thrombin-cleavable or that the drug in the nanoparticles is plasmin, it would have been obvious to one of ordinary skill in the art to add these elements to the nanoparticles of Sun because Xu teaches that fibrinolytic agents, such as tPA, may be shielded from the bloodstream in a nanoparticle and then released specifically at a thrombus by cleavage of a thrombin-cleavable peptide conjugated to a membrane lipid that forms part of the nanoparticle and because Marder teaches that plasmin has a significantly higher safety margin than tPA. One of ordinary skill in the art would have a reasonable expectation that adding the thrombin-cleavable peptide of Xu and the plasmin of Marder to the nanoparticles of Sun would successfully result in the production of nanoparticles that successfully targeted blood clots, protected plasmin from α2-antiplasmin and then specifically released plasmin upon interacting with the clot, and caused thrombolysis.
Therefore, claims 1-16 and 18 are rendered obvious by Sun in view of Xu and Marder and are rejected under 35 U.S.C. 103.
Claims 1-16, 18, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al., Nanoscale 12: 21255-21270 (2020), in view of Xu et al., ACS Nano 13: 8577-8588 (2019), Marder et al., Stroke 41(suppl. 1): S45-S49 (2010), and US patent application publication 2018/0318443 filed by Sen Gupta et al., published 11/08/2018.
As discussed above, claims 1-16 and 18 are rendered obvious by Sun in view of Xu and Marder. In addition, the portions of the references cited for instant claim 1 above are applicable to the analogous limitations in instant claim 22. However, Sun, Xu, and Marder do not teach that the thrombin cleavable peptide is conjugated to stearyl amine, as recited in instant claims 21-22.
Sen Gupta teaches nanoparticles that target activated platelets in blood clots and deliver drugs to them (see entire document, including paragraphs 0059-0062). The nanoparticles may have platelet-targeting moieties arranged on their surfaces and may be liposomes (paragraphs 0062-0063). The lipids to which the platelet-targeting moieties may be attached may include stearyl amine (paragraphs 0063 and 0067; cf. claims 21-22).
While Sun, Xu, and Marder do not teach that the thrombin cleavable peptide in the liposomal nanoparticle rendered obvious by their teachings is conjugated to stearyl amine, it would have been obvious to do so because Sen Gupta teaches that stearyl amine is a lipid that can be used to make liposomal nanoparticles targeted to activated platelets in blood clots and may serve as an attachment for peptides. One of ordinary skill in the art would have a reasonable expectation that attaching the thrombin-cleavable peptide in the liposomal nanoparticle rendered obvious by the combination of Sun, Xu, and Marder to the stearyl amine of Sen Gupta would successfully result in the production of a platelet- and fibrin-targeted liposomal nanoparticle encapsulating plasmin that can be cleaved by thrombin to release plasmin at the site of a blood clot.
Therefore, claims 1-16, 18, and 21-22 are rendered obvious by Sun in view of Xu, Marder, and Sen Gupta and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the 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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Allowable Subject Matter
Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art to claim 17 is found in the teachings of Sun, Xu, and Marder, as discussed above. However, these references do not teach or suggest that the sequence of the thrombin-cleavable peptide is DVTPRC. As such, claim 17 is free of the prior art. Because claim 17 depends from a rejected base claim, however, claim 17 is objected to.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 07/10/2026
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