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 .
Withdrawal of Rejections
The response and amendments filed on 04/30/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 112(b) for indefiniteness have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection as set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 112(b), Indefiniteness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 6 is rejected under 35 U.S.C. 112(b) 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 6 recites the transitional phrase “can comprise”; however, it is unclear if the lipids following “can comprise” are required, or if the language “can comprise” means that the lipids are optional since the word “can” results in the claim reading as if the lipids are optional. For the purposes of applying prior art, the Examiner has interpreted the lipids recited in claim 6 to be optional.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the previous 35 U.S.C. 112(b) rejections (remarks, pages 8-9), as previously mentioned, all previous 35 U.S.C. 112(b) rejections have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection are set forth above.
Maintained Rejections
Claim Rejections – 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Moon (WO 2017/223085; Date of Publication: December 28, 2017 – cited in the IDS filed on 05/10/2024) in view of Maloney (U.S. Patent No. 10,752,581; Date of Publication: August 25, 2020 – cited in the IDS filed on 05/10/2024).
Moon’s general disclosure relates to “nanoparticles associated with (e.g., complexed, conjugated, encapsulated, absorbed, adsorbed, admixed) biomacromolecule agents configured for treating, preventing or ameliorating various types of disorders” (see, e.g., Moon, abstract). Moreover, Moon discloses that the nanoparticle is synthetically produced and comprises a mixture of at least one phospholipid and at least one HDL apolipoprotein or apolipoprotein mimetic (see, e.g., Moon, pg. 4, lines 3-4). Additionally, Moon discloses that the nanoparticles can be used as a therapeutic for treating and/or preventing cardiovascular related disorders (see, e.g., Moon, pg. 113, lines 27-29).
Regarding claim 1 pertaining to the composition, Moon teaches a synthetic HDL (sHDL) nanoparticle (see, e.g., Moon, abstract), that comprises a mixture of a phospholipid, such as 1-2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) (see, e.g., Moon, Examples 5-7) and HDL apolipoprotein or apolipoprotein mimetic (see, e.g., Moon, pg. 4, lines 3-4).
Regarding claim 2 pertaining to sustained release, Moon teaches that the sHDL nanoparticle mixture comprising a phospholipid and apolipoprotein exhibited sustained release of their cargo (i.e., antigen/CpG adjuvant (Ag/CpG)) within endosomes/lysosomes over 24 hours (see, e.g., Moon, Figure 20).
Regarding claims 4 and 8 pertaining to the HDL apolipoprotein, Moon teaches that the HDL apolipoprotein can be an HDL apolipoprotein mimetic (see, e.g., Moon, abstract).
Regarding claim 5 pertaining to the molar ratio, Moon teaches “the sHDL nanoparticles have a molar ratio of phospholipid/ HDL apolipoprotein from 2 to 250 (e.g., 10 to 200, 20 to 100, 20 to 50, 30 to 40)” (see, e.g., Moon, pg. 67, lines 10-11).
Regarding claim 6 pertaining to the lipid component, Moon teaches that the lipid component is 1-2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) (see, e.g., Moon, Examples 5-7). See 112(b) rejection above regarding this.
Regarding claim 7 pertaining to the charge of the lipid component, Moon teaches that the lipid component can be neutral (i.e., uncharged) (see, e.g., Moon, pg. 90, lines 24-25).
Regarding claim 9 pertaining to the ApoA-I mimetic, Moon teaches SEQ ID NO: 4, which encodes a “22A” ApoA-I mimetic (see, e.g., Moon, Examples 1-4), and which has 100% sequence identity to instant SEQ ID NO: 4 (see, e.g., Office Action Appendix).
However, Moon does not teach: N-2-benzothiazolyl-4-[[2-hydroxy-3-methoxyphenyl)methyl]amino]-benzenesulfonamide (ML355) (claim 1); or wherein the sHDL-ML355 is capable of inhibiting platelet aggregation, inhibiting thrombosis formation, inhibiting vessel occlusion, and/or inhibiting platelet associated 12-LOX activity (claim 3).
Maloney’s general disclosure relates to identification of compounds that are potent and selective inhibitors of 12-LOX (see, e.g., Maloney, “Summary of the Invention”, col. 4, lines 22-23). Moreover, Maloney discloses that compound ML355 is an inhibitor of 12-LOX (see, e.g., Maloney, Figures 4-5). Additionally, Maloney teaches that treatment of platelets with ML355 results in decreased platelet aggregation (see, e.g., Maloney, Figures 11A-B).
Regarding claims 1 and 3 pertaining to ML355, Maloney teaches ML355 for inhibiting 12-LOX activity (see, e.g., Maloney, Figures 4-5) and decreasing platelet aggregation (see, e.g., Maloney, Figure 11A-B).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Moon’s sHDL nanoparticle comprising a lipid and an HDL apolipoprotein, wherein the sHDL nanoparticle also comprises ML355, as taught by Maloney. One would have been motivated to do so because Moon teaches that the sHDL, lipid, HDL apolipoprotein mixture produces a stable, ultrasmall nanoparticle capable of protecting and delivering cargo for biotherapeutics including treating cardiovascular disorders (see, e.g., Moon, pg. 1, lines 20-29). Additionally, Moon teaches that this nanoparticle platform is generally applicable for personalize therapeutics with a wide range of bioactive molecules (see, e.g., Moon, pg. 2, lines 24-25). Moreover, Maloney teaches that ML355 is an inhibitor of 12-LOX (see, e.g., Maloney, Figures 4-5), which has therapeutic implications for cancer, inflammatory diseases, neurodegenerative diseases, diabetes, cardiovascular disease, etc. (see, e.g., Maloney, “Background of the Invention”, cols. 1-3). Therefore, ML355 is a molecule that can be used to treat or prevent 12-LOX mediated diseases or disorders (see, e.g., Maloney, col. 5, lines 27-30 & Figures 4-5). Therefore, based on the teachings of Moon and Maloney, it would have been obvious to combine sHDL comprising a lipid component and an HDL apolipoprotein component, with ML355 in order to inhibit 12-LOX mediated disorders. Moreover, based on the teachings of Moon and Maloney, the sHDL nanoparticle mixture would be capable of protecting and delivering the ML355 cargo for 12-LOX mediated diseases. One would have expected success because Moon and Maloney teach the sHDL nanoparticle and ML355 moiety for treatment of various diseases and disorders, i.e. cardiovascular diseases.
Regarding claim 3 pertaining to the effects exhibited by sHDL-ML355, the ability of sHDL-M355 to inhibit platelet aggregation, inhibit thrombosis formation, inhibit vessel occlusion, and inhibit platelet associated 12-LOX activity is considered intended use for the claimed composition. The combined prior art of Moon and Maloney teaches producing and administering the same sHDL-ML355 composition; therefore, the composition taught by Moon and Maloney would be capable of performing the intended use of inhibiting platelet aggregation, inhibiting thrombosis formation, inhibiting vessel occlusion, and/or inhibiting platelet associated 12-LOX activity. Furthermore, as claimed in instant claim 3, sHDL-ML355 inhibits platelet aggregation, thrombosis formation, vessel occlusion, and platelet associated 12-LOX activity; therefore, the composition taught by Moon and Maloney would inherently have these properties (see, e.g., 2163.07(a)).
Examiner’s Response to Arguments
Applicant's arguments filed 04/30/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s argument that there is no teaching, suggestion, or motivation to combine sHDL, as taught by Moon, and ML355, as taught by Maloney, in order to treat thrombosis (remarks, page 10), this argument is not persuasive for multiple reasons:
First, the claims are directed to a composition, not a method; therefore, it is obvious to incorporate a desired active ingredient or composition, such as ML355, as taught by Maloney, into Moon’s delivery system (see, e.g., Moon, pg. 4, lines 3-4).
Secondly, Moon teaches sHDL nanoparticles associated with biomacromolecule agents for treating, preventing, or ameliorating various types of disorders (see, e.g., Moon, abstract). Moon teaches that the sHDL, lipid, HDL apolipoprotein mixture produces a stable, ultrasmall nanoparticle capable of protecting and delivering cargo for biotherapeutics including treating cardiovascular disorders (see, e.g., Moon, pg. 1, lines 20-29). Moreover, Maloney teaches that ML355 is an inhibitor of 12-LOX (see, e.g., Maloney, Figures 4-5), which has therapeutic implications for cancer, inflammatory diseases, neurodegenerative diseases, diabetes, thrombosis, cardiovascular disease, etc. (see, e.g., Maloney, “Background of the Invention”, cols. 1-3). Therefore, one would be motivated to combine the sHDL, as taught by Moon, with ML355, as taught by Maloney, in order to treat cardiovascular diseases. Since, Moon and Maloney both teach delivery of biotherapeutic agents that treat cardiovascular diseases, Moon and Maloney are not combined based on hindsight because it would be obvious to combine therapeutic agents that treat both cardiovascular diseases. The incorporation of a therapeutic depending on the desired treatment is obvious.
Regarding Applicant’s arguments that the combination of Moon and Maloney does not result in the claimed level of inhibition of platelet aggregation or thrombosis (remarks, page 10), this argument is not persuasive because there is no claimed level of inhibition of platelet aggregation or thrombosis. Furthermore, combining sHDL, as taught by Moon, and ML355, as taught by Maloney, would inherently result in the same level of inhibition of platelet aggregation or thrombosis as the instant application because the Moon and Maloney teach the instantly claimed composition.
Regarding Applicant’s arguments that the combination of sHDL and ML355 produces greater inhibition of platelet aggregation than either component alone, which is not disclosed in Moon (remarks, pages 10-11), this argument is not persuasive for multiple reasons:
First, as stated above, the claims are directed to a composition, not a method; therefore, it is obvious to incorporate a desired active ingredient or composition, such as ML355, as taught by Maloney, into Moon’s delivery system (see, e.g., Moon, pg. 4, lines 3-4).
Second, Moon teaches that the sHDL, lipid, HDL apolipoprotein mixture produces a stable, ultrasmall nanoparticle capable of protecting and delivering cargo for biotherapeutics including treating cardiovascular disorders (see, e.g., Moon, pg. 1, lines 20-29). Moreover, Maloney teaches that ML355 is an inhibitor of 12-LOX (see, e.g., Maloney, Figures 4-5), which has therapeutic implications for cancer, inflammatory diseases, neurodegenerative diseases, diabetes, thrombosis, cardiovascular disease, etc. (see, e.g., Maloney, “Background of the Invention”, cols. 1-3). Therefore, it is obvious to combine the active compounds that treat cardiovascular diseases and thrombosis.
Thirdly, “inhibiting platelet aggregation, inhibiting thrombosis formation, inhibiting vessel occlusion, and/or inhibiting platelet associated 12-Lipoxygenase (12-LOX)” as recited in claim 3 is a property of the compound. Therefore, Moon and Maloney teach the instantly claimed composition, which would result in these claimed properties. Moreover, Chung (High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion; 2016 - Art of Record – cited in the IDS filed on 05/10/2024) teaches that high-density lipoprotein prevent von Willebrand factor self-association resulting in an antithrombotic property of this cardioprotective lipoprotein (see, e.g., Chung, Introduction, pgs. 637-638). Pajkrt (Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia; 1997 – Art of Record – cited in the IDS filed on 05/10/2024) also teaches that “HDL can also effect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation” (see, e.g., Pjkrt, Summary, pg. 303). Therefore, based on the prior art teaching that HDL inherently has antithrombic properties, it would be expected that combining HDL and another antithrombic agent, such as ML355, as taught by Maloney above, would result in enhanced, or even synergistic, antithrombic activity, compared to each component alone (see, e.g., In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)). Therefore, one of ordinary skill in the art would expect the incorporation of an platelet aggregation inhibitor to reduce aggregation and occlusion
Fourthly, even if there is enhanced antiplatelet activity by combining sHDL with ML355, the results are not commensurate in scope with the claimed invention. The results shown in Figure 5 of the instant specification rely on washing human platelets in different ML355 formulations for 15 minutes with specific concentrations of ML355 (10 µM) and sHDL (100 µg/mL), intravenously administering ML355 at 1.5 mg/kg and sHDL at 50 mg/kg for 24 hours followed by platelet isolation, and incubation of all formulations with thrombin (0.1 and 0.25 nM thrombin) (see, e.g., instant specification, Figure 5, pgs. 11-12). Therefore, the results are relying on various concentrations of ML355 and sHDL, as well as specific administration and culturing parameters, all of which are not part of the instantly claimed invention. Therefore, the results are not commensurate in scope with the instantly claimed invention.
Art of Record
Chung DW, Chen J, Ling M, Fu X, Blevins T, Parsons S, Le J, Harris J, Martin TR, Konkle BA, Zheng Y, López JA. High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion. Blood. 2016 Feb 4;127(5):637-45. doi: 10.1182/blood-2014-09-599530. Epub 2015 Nov 9. PMID: 26552698; PMCID: PMC4742551.
Pajkrt D, Lerch PG, van der Poll T, Levi M, Illi M, Doran JE, Arnet B, van den Ende A, ten Cate JW, van Deventer SJ. Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia. Thromb Haemost. 1997 Feb;77(2):303-7. PMID: 9157586.
Conclusion
Claims 1-9 are rejected.
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.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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