Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/20/2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objects are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection
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.
Claims 1-7, 9-15 and 33 are 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. The genus “polyester-derived nanoparticles” is unclear as the exact definition of “derived” in the chemical arts depends on the specific context. A derivative may be a compound that is derived from a similar compound by a chemical reaction, or that can be imaged to arise from another compound, if one atom or group of atoms is replaced with another atom or group of atoms. It’s unclear in what manner a nanoparticle is “derived” from a polyester and what characteristic a nanoparticle must have to be considered “polyester-derived” and what characterstic a nanoparticle has to be excluded from this genus.
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.
The Declaration of Michael Cho, PhD, filed on 2/20/2026 under 37 CFR 1.131(a) has been considered but is ineffective to overcome the following rejections for the reasons given further below.
Claims 1-7, 9, 11-15, 17-19, 21-25 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over US 20110143993 to Langer (IDS filed 4/18/2022) in view of Eakin (Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury, PLUS ONE, 2014, 9(4), e906617) in further view of Serbest (Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma, The FASEB Journal, express article 10.1096/fj.05-4024fje, pages 1-27, 2005) in further view of Mo (Expression of P-selectin VCAM-1, and PSGL-1 in traumatic deep venous thrombosis, Int J Clin Exp Pathol 2016;9(3):3403-3409). Langer teaches a composition (abstract, " ... The ligands are useful when attached to a substrate to be in contact with endothelial surfaces, especially those where drug delivery ... release from a drug delivery reservoir ... by administration intravenously in the form of nano or microparticles ... "; para [0022], "FIG. 7 A is a schematic of targeted lipid-polymeric NP design. The targeted lipid-polymeric nanoparticles have a core-shell structure: soybean lecithin and peptide-conjugated ... forms the shell; poly(lactic-co-glycolic acid) (PLGA) encapsulating paclitaxel forms the core") comprising: a population of polyester derived nanoparticles (abstract, " ... The ligands are useful when attached to a substrate to be in contact with endothelial surfaces, especially those where drug delivery ... release from a drug delivery reservoir ... by administration intravenously in the form of nano or microparticles ... "; para [0053], "In the preferred embodiment, the particles are formed from biocompatible and/or biodegradable polymers such as polylactic and/or polyglycolic acids .. ."; para [0058], "In the most preferred embodiment, PLGA is used as the biodegradable polymer''; para [0022], "FIG. 7 A is a schematic of targeted lipid-polymeric NP design. The targeted lipid-polymeric nanoparticles have a core-shell structure: soybean lecithin and peptide-conjugated ... forms the shell; poly(lactic-co-glycolic acid) (PLGA) encapsulating paclitaxel forms the core"; see instant specification pg 2 lines 20-27); wherein each polyester derived nanoparticle comprises: a) a therapeutic agent encapsulated therein for treating traumatically injured, inflamed, diseased, or disrupted endothelial cells (abstract, " ... The ligands are useful when attached to a substrate to be in contact with endothelial surfaces, especially those where drug delivery ... release from a drug delivery reservoir ... by administration intravenously in the form of nano or microparticles ... targeting or to increase adhesion to endothelial surfaces. The nanoparticle technology can be used to treat injured vasculature ... "; para [0070], "For vascular targeting ... nanoparticle design allows for: (i) improved drug encapsulation; (ii) sub-100 nm NPs for vascular targeting"; para [0022], "FIG. 7 A is a schematic of targeted lipid-polymeric NP design. The targeted lipid-polymeric nanoparticles have a core-shell structure: soybean lecithin and peptide-conjugated ... forms the shell; poly(lactic-co-glycolic acid) (PLGA) encapsulating paclitaxel forms the core"), and b) a targeting ligand bound to the nanoparticle (abstract, "Peptides that selectively bind to antigens exposed in vascular disease or dysfunction ... The ligands are useful... by administration intravenously in the form of nano or microparticles ... "; para [0047], "The endothelial basement membrane targeting peptide ligands can be bound to any substrate, including substrates formed of polymer ... The ligands can be used to target and/or adhere the materials to disrupted or injured endothelium"; para [0106], "Passive targeting will probably dominate in the NP size range of 100-500 nm, but ultimately, nanoparticle retention after 24-72 hours due to targeting would probably be greater than non-targeted NP groups"; para [0022], "FIG. 7 A is a schematic of targeted lipid-polymeric NP design. The targeted lipid-polymeric nanoparticles have a core-shell structure: soybean lecithin and peptide-conjugated ... forms the shell; poly(lactic-co-glycolic acid) (PLGA) encapsulating paclitaxel forms the core"), wherein the targeting ligand binds to a biomarker for the injured, inflamed, diseased, or disrupted endothelial cells (abstract, "Peptides that selectively bind to antigens exposed in vascular disease or dysfunction ... The ligands are useful. .. "; para [0038], "Peptides which bind specifically to epitopes exposed following vascular breach or other injury can be identified by screening of peptide libraries. This is demonstrated by the examples where peptides which bind specifically to antigen exposed following vascular breach or other injury"). Langer further teaches wherein the population of nanoparticles has an average particle size ranging from about 10 nm to about 1000 nm, such as from about 100 nm to about 500 nm, or from about 120 nm to about 300 nm (para [0049], ""nanoparticle" is a particle having an average diameter on the order of nanometers (i.e., between about 1 nm and about 1 micrometer ... "; para [0106], "Passive targeting will probably dominate in the NP size range of 100-500 nm, but ultimately, nanoparticle retention after 24-72 h due to targeting would probably be greater than non-targeted NP groups"). Langer further teaches wherein the population of nanoparticles has a polydispersity of 0 (of 0.1 or less) (claims 1 and 2). There may be more than one therapeutic agent (paragraph 63). The nanoparticles comprise PLGA (paragraphs 82-83, and 174-188). The target agent may be a peptide (paragraph 3). The therapeutic agent is delivered with a targeting ligand (a non-biological material) (paragraph 14). The therapeutic agent may be paclitaxel (an agent which when administered alone exhibits negligible to no oral bioavailability (paragraph 15).
Langer fails to teach wherein the biomarker is selected from P-selectin, E-selectin, or L-selectin, incorporation of a poloxamer surfactant and antioxidant into the composition, that the molecular weight may be 1,000 to 50,000 (paragraph 77), and further fails to teach to teach the weight ratios recited in claim 13.
Mo teaches biomarkers such PSGL-1 (a targeting ligand that binds to P-selectin) is a biomarker for use in traumatic deep venous thrombosis (abstract; page 3408, left column, second to lats paragraph).
Eakin teaches that N-acetylcysteine (an antioxidant) is used to treat trauma of the brain (abstract; Introduction; discussion).
Serbest teaches that poloxamer 188 (a poloxamer surfactant) is used for neuroprotection after mechanical trauma (abstract).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to incorporate PSGL-1 as the targeting ligand of Langer. The motivation for this would be to provide a biomarker for use in traumatic deep venous thrombosis. PSGL-1 is a targeting ligand that binds to P-selectin, a biomarker for use in traumatic deep venous thrombosis. It would have been further obvious to incorporate N-acetylcysteine into the composition of Langer. The motivation for this would be to increase the efficacy of the formulation for treatment of trauma of the brain. It would have been further obvious to incorporate poloxamer 188 into the composition of Langer. The motivation for this would be to provide a surfactant for use in neuroprotection after mechanical trauma. It would have been further obvious to optimize the molecular weight of Langer to improve the efficacy of the formulation. In this way, the artisan would find the present range through routine experimentation. The prior art provides sufficient guidance to this end as Langer teaches a molecular weight of 1,000 to 50,000, which overlaps with the present range of 5,000 to 100,000. Similarly, it would have been obvious to find the presently claimed weight ratios through routine experimentation. “’[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” MPEP § 2144.05, II.
Claims 1-7, 9-15, 17-19, 21-25 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over US 20110143993 to Langer (IDS filed 4/18/2022) in view of Eakin (Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury, PLUS ONE, 2014, 9(4), e906617) in further view of Serbest (Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma, The FASEB Journal, express article 10.1096/fj.05-4024fje, pages 1-27, 2005) In further view of Mo (Expression of P-selectin VCAM-1, and PSGL-1 in traumatic deep venous thrombosis, Int J Clin Exp Pathol 2016;9(3):3403-3409) in further view of Holmes (Safety and Efficacy of Doxycycline, Clinical Medicine Therapeutics, Vol 1, 2009). The relevant portions of Langer, Eakin,, Serbest, and Mo are given above. In addition, Langer teaches that the therapeutic agent may be an antibiotic (paragraph 102). The relevant portions of Langer, Easkin, Serbest, and Mo are given above.
Langer fails to teach incorporation of doxycycline.
Homes teaches that doxycycline is an antibiotic (abstract).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to use doxycycline as the active agent of Langer. The motivation for this is that by providing doxycycline as the active agent of Langer will provide an antibiotic, as desired by Langer.
Response to Arguments
Applicant’s arguments have been fully considered but they are not deemed to be persuasive.
Regarding applicant’s argument that the references do not satisfy the limitation “wherein the biomarker is selected from P-selectin, E-selectin, or L-selectin,” the examiner’s response is Mo teaches biomarkers such PSGL-1 (a targeting ligand that binds to P-selectin) is a biomarker for use in traumatic deep venous thrombosis
Regarding applicant’s argument that Langer does not teach a poloxamer surfactant and an antioxidant, the examiner’s response is that it would have been obvious to incorporate these two components into the composition of Langer for the reasons set forth in the new grounds of rejections above.
Regarding applicant’s argument that one would not be motived to combine poloxamer compounds and antioxidants because it is well known in the art that nanoparticles are highly complex and sensitive to component interactions, the examiner’s response is that the nanoparticle art is a well developed art, and adjusting the properties of nanoparticles by adding components that provide certain functionalities is well established. The examiner appreciates the declaration of Michael Cho, and deems that the results presented therein are unexpected. However, the results are not commensurate in scope with the claimed invention as results are limited to a specific nanoparticle comprising a polyester, a therapeutic agent comprising a poloxamer surfactant and antioxidant, and targeting ligand in specific amounts and relative ratios to each other, whereas the claimed composition includes polyester derived nanoparticles, which is a larger genus than polyester nanoparticles, therapeutic agents across the scope therapeutic agents comprising poloxamer surfactants across the scope of poloxamer surfactants and antioxidants across the scope of antioxidants, and targeting ligands bound to the nanoparticle across the scope of targeting ligands that bind to a biomarker for injured, inflamed, diseased, or disrupted endothelial cells, wherein the biomarker is selected from P-selectin, E-selectin, or L-selectin. The artisan would not accept that the results, which are a few limited embodiments of the claimed invention, would necessarily extend over the scope of the much broader claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618 March 7, 2026
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