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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 10/15/2025 wherein claims 1-26 and 51-54 were canceled and claims 47-50 and 55-58 were amended. In addition, the Examiner acknowledges receipt of the amendment filed 8/7/2025 and 3/5/2024. Also, the Examiner acknowledges the substitute specification and abstract filed 3/7/2024.
Note(s): Claims 27-50 and 55-58 are pending.
Priority
This application is a 371 of PCT/CN2022/117091 filed 9/5/2022 and claims benefit to PCT/CN2021/116681 filed 9/6/2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 USC 119 (a) – (d). The certified copy has been filed 3/5/2024 in the pending application.
While a certified copy was submitted, an English language translation is not of record. Should Applicant desire to obtain the benefit of foreign priority under 35 USC 119 (a) – (d) prior to declaration of an interference, a certified English language translation of the foreign application should be submitted. 37 CFR 41.154(b) and 41.202(e). Failure to provide the certified translation may result in no benefit being accorded for the non-English document.
Note(s): The earliest effective filing date is 9/5/2022 because the pending invention is fully disclosed in the PCT/CN2022/117091. It should be noted that PCT/CN2021/116681 is a non-English document and no English translation is of record.
Claim Interpretation
Pending claim 27 is directed to a liposome nanocarrier delivery system comprising a liposome carrier and a substance wherein the liposome carrier comprises a phospholipid and cholesterol; the liposome nanocarrier delivery system is modified with a targeting ligand which is hyaluronic acid and DSPE-PEG2000-NH2 coupled through an amide bond; and the final concentration of the targeting ligand is 10 – 100 µg/ml.
Note(s): It is unclear whether or not the substance is present as one of the final components of the delivery system or if the substance is what is modified in the delivery system to become the targeting ligand.
Claim 34 is directed to a method of preparing a liposome nanocarrier delivery system as set forth therein.
Claim 45 is directed to a medicine as set forth therein.
Claims 47-50, 57, and 58 are directed to use of a medicine as set forth therein.
Claims 55 and 56 are directed to use of a nanocarrier delivery system as set forth therein.
Applicant’s Election
Applicant's election with traverse of Group I (pending claims 27-33 and 45) filed 1/16/2026 is acknowledged. The traversal is on the grounds that (1) the nanocarrier system proves that the actively encapsulated formation has high targeting ability and an unexpected plaque regression effect (2) the prior art referenced in the in the lack of unity discussion (Zhao et al, Carbohydrate Polymers, 2019, vol. 203, pages 356-368) does not teach plaque targeting and the final effect on atherosclerosis. In addition, it is asserted the other reference (Li et al, Journal of controlled Release, 2018, Vol. 288, pages 96-110) appearing in the lack of unity discussion silent on the targeting ligand coupled through an amide bond and as such one would not be motived to use the liposome nanocarrier delivery system for preventing and/or treating atherosclerosis or an atherosclerosis related disease. (3) Still, it is asserted that the final concentration of the targeting ligan has an unexpected technical effect.
Applicant assertions were considered and deemed non-persuasive for reasons in the lack of unity discussion previously of record and those below. Independent claim 27 is directed to a product wherein the components are utilized in the art. Applicant is respectfully reminded that a product is evaluated on the components that make up the product, not on the intended use of the product which is generally presented as a method of use claim. Thus, if the prior art and cited art disclose overlapping components, the properties associated with Applicant’s invention would also be expected to be present with the prior art invention as well (see MPEP 2112.01, Section II).
Furthermore, as indicated by the cited prior art below, the invention is not distinguished over the prior art of record. Hence, the restriction requirement is still deemed proper and is therefore made FINAL.
The Examiner acknowledges receipt of Applicant’s election of the species wherein the phospholipid is distearoylphosphatidylcholine (DSPC) and DSPE-PEG2000; the liposome carrier is DSPC, cholesterol, and DSPE-PEG2000; the solvent is water; HPD and rosuvastatin calcium are also present in the liposome nanocarrier system; and the targeting ligand is hyaluronic acid and DSPE-PEG2000. Claims 27-33 and 45 read on the elected species.
Initially, Applicant’s elected species was searched. No prior art was found which could be used to reject the claims. Thus, the search was extended to that in the cited prior art below. The search was not further extended because prior art was found which could be used to reject the claims.
Withdrawn Claims
Claims 34-44, 46-50, and 55-58 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Information Disclosure Statement
The information disclosure statement filed 6/5/2024; 1/27/2025; 4/24/2025; 10/20/2025; and 1/16/2026 were considered.
Written Description Rejection
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 27-33 and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection.
(I) The pending application does not sufficiently describe the invention or provide support as it relates to prevention of atherosclerosis-related diseases.
(II) In addition, the pending application does not sufficiently describe the invention as it relates to atherosclerosis-related diseases other than (1) coronary atherosclerotic heart disease selected from acute coronary syndrome, asymptomatic myocardial ischemia-latent coronary heart disease, angina pectoris, myocardial infarction, ischemic heart disease, sudden death, and in-stent restenosis; (2) cerebral atherosclerosis selected from cerebral ischemic stroke, and hemorrhagic apoplexy; (3) peripheral vascular atherosclerosis selected from carotid atherosclerosis, vertebral atherosclerosis, subclavian atherosclerosis, occlusive peripheral atherosclerosis, retinal atherosclerosis, renal atherosclerosis, lower extremity atherosclerosis, upper extremity atherosclerosis, mesenteric atherosclerosis, and atherosclerotic impotence; (4) aortic dissection; (5) hemangioma; (6) thromboembolism; (7) heart failure; and (8) cardiogenic shock. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
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 27-33 and 45 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.
Claims 27-33 and 45: Independent claim 27 is ambiguous for the following reasons: according to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under, in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed to liposome nanocarrier delivery systems comprising any substance. While it is proposed that the substance is used for preventing and/or treating atherosclerosis or an atherosclerosis-related disease, independent claim 27 is directed to a product upon which patentability is based on the components of the product, not the intended use of the product. Thus, there are an infinite number of substances encompassed by the term ‘substance’.
Similarly, the claim is ambiguous due to the inability to envision the massive number of distinct alternative members such that one skilled in the art cannot determine the metes and bounds of the claim. In addition, there is also an unlimited number of substances that ‘prevent and/or treat atherosclerosis or an atherosclerosis-related diseases’. Hence, due to an inability to envision all of the substances (compounds) encompassed therein, the claim is deemed to be vague and indefinite.
Since claims 28-33 and 45 depend upon independent claim 27 for clarity, those claims are also vague and indefinite.
Claims 27-33 and 45: Claim 27 is ambiguous because the ‘substance’ (line 2) is confusing. The claim disclose that the delivery system comprises a liposome carrier and a substance (line 2). The liposome carrier comprise a phospholipid and cholesterol (line 5). Then, the claim discloses that the delivery system is modified with a targeting ligand (line 6. The targeting ligand is hyaluronic acid and DSPE-PEG2000-NH2 (lines 6-7). Is the modification to the substance, the actual substance itself, replacement of the substance, or is the substance an additional component? Is not clear if Applicant intend ‘modification’ to mean that a component is added or replaced. Since claims 28-33 and 45 depend upon independent claim 27 for clarity, those claims are also vague and indefinite.
Claim 30: The claim is ambiguous because it is unclear what substances are actually being claimed. Specifically, line 3 discloses that the substance is ‘a weakly acidic substance’. Lines 5-8 are directed to ‘statins’ fibrates, antiplatelet drugs, PCSK9 inhibitors, anticoagulant drugs, angiotensin converting enzyme inhibitors, calcium ion antagonists, MMPs inhibitors, beta receptor blockers, and glucocorticoid’. Lines 10-13 are directed to substances that include statins like those in lines 5-8 and 15-16. Line 10-13 disclose lovastatin, atorvastatin, rosuvastatin (this substance is also in line 15), simvastatin, fluvastatin, pitavastatin (this substance is also in line 15), pravastatin (this substance is also in line 15), bezafibrate (this substance is encompassed in line 5), ciprofibrate (this substance is also in line 5), gemfibrozil, aspirin, acemetacin, sodium ozagrel, beraprost sodium, and tirofiban. Lines 15-16 are directed to substances that are statins which include rosuvastin and pravastatin which are found in earlier portions of the claims (line 15).
The claim contains various overlapping subject matter. In addition, in some areas (e.g., lines 5 and 15), there is general terminology (e.g., statin) and in other lines (e.g., line 15) there are species disclosed that are encompassed by the general terminology (e.g., specific statins). Still, there is the use of a ‘substance’ that is selected from ‘a weakly acidic substance’. Is the substances listed in lines 10-13 and atorvastin the actual substances that Applicant intends to claim? These are the specific species encompassed by the more general terminology in other lines of the claim.
Claim 32: The claim is confusing for the following reasons. The claim is outside the scope of independent claim 27. Specifically, claim 32 discloses that the final concentration of the targeting ligand is 100 ± 24 µg/ ml which is a range of 76 µg/ ml to 124 µg/ ml. Pending claim 27 only allows for a maximum of 100 µg/ ml to be present so the upper end of the range is outside the scope of independent claim 27.
103 Rejection
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.
Claims 27-33 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (Langmuir, 2010, Vol. 26, No. 13, pages 11140-11144).
Pending claim 27 is directed to a liposome nanocarrier delivery system comprising a liposome carrier and a substance wherein the liposome carrier comprises a phospholipid and cholesterol; the liposome nanocarrier delivery system is modified with a targeting ligand which is hyaluronic acid and DSPE-PEG2000-NH2 coupled through an amide bond; and the final concentration of the targeting ligand is 10 – 100 µg/ml.
Note(s): It is unclear whether or not the substance is present as one of the final components of the delivery system or if the substance is what is modified in the delivery system to become the targeting ligand.
Claim 28 is directed to various phospholipids therein which include distearoylphosphatidylethanolamine.
Claim 31 disclose that the average molecular weight of the hyaluronic acid is 12,000 to 16,000.
Claim 32 discloses that the final concentration of the target ligand is 76 µg/ml to 124 µg/ml.
Claim 33 is directed to small, large, and multilamellar liposomes.
Claim 45 is directed to a medicine comprising the nanocarrier delivery system and a pharmaceutically acceptable carrier.
Zhang et al is directed to polyethylene glycolated phospholipid substances. Specifically, small unilamellar nanocarrier vesicles were generate from 1,2-dimyristoylphosphatidylcholine (DMPC) with varying molar amounts of 1,2-distearoyl-sn-glycero-3-phosphoetholamine-N-[methoxy(poly(ethylene glycol))-2000 (DSPE-PEG2000) and fused into (modified with) membranes on different polymer-modified silicon dioxide surfaces including chitosan, poly-lysine, and hyaluronic acid. The thickness of PEGylated lipid membrane varied as the molar fraction of PEG increased. Cholesterol was incorporated into the mixture to improve the structural stability of the lipid membrane. Different amounts of cholesterol alter the thickness and surface morphology of the membrane. The liposome preparation is extruded using a filter with an average pore size of 50 nanometers to generate a phospholipid containing liposome nanocarrier delivery system (see entire document, especially, abstract; page 11140, right column, second complete paragraph; pages 11140-11141, bridging paragraph; page 11141, left column, first and second complete paragraphs; page 11141, Figures 3-5).
On page 11141, the liposome preparation process is disclosed. Briefly, the DSPE-PEG2000 and cholesterol are mixed with SMPC in chloroform. The solvent is evaporated and the thin film remaining is rehydrated with PBS solution to a concentration of 1 mM DMPC. Next, the solution clarified with and extruded through a filter having an average pore size of 50 nanometers.
Zhang et al disclose that one can vary the amount of DSPE-PEG2000 (the other component being optimized in the ratio) from 1.5-5 mole percent (page 11143, left and right columns, bridging paragraph).
The targeting ligand comprises hyaluronic acid and DSPE-PEG2000. It would be obvious to a skilled artisan to optimize the amount because the Zhang et al disclose various way of optimizing the liposome components, desired property of interest (e.g., thickness and surface morphology of the membrane). Still, Zhang et al disclose that one can vary the amount of DSPE-PEG2000 (the other component being optimized in the ratio) from 1.5-5 mole percent (page 11143, left and right columns, bridging paragraph; page 11144, Figure 9). According to MPEP 2144.05, generally differences in things such as concentration wherein the prior art discloses evidence indicating that such factor is critical and may be optimized, determining optimum workable ranges by routine experimentation is expected.
Zhang et al disclose that the hyaluronic acid has a molecular weight of 60,000 (page 11141, left column, second complete paragraph). However, it is disclosed substrate surface modification occurred such that the concentration of hyaluronic acid ended up being 1 mM (page 11141, left column, first complete paragraph). In addition, the abstract discloses that one can vary various components to optimize various desired properties of the vesicles as discussed supra. According to MPEP 2144.05, generally differences in things such as concentration wherein the prior art discloses evidence indicating that such factor is critical and may be optimized, determining optimum workable ranges by routine experimentation is expected. Thus, it would be obvious to the skilled artisan to alter the molecular weight of hyaluronic acid depending upon the modifications that thereof. For example, in the abstract, it is disclosed that different polymer modifications of silicon dioxide surfaces including those to hyaluronic acid may be made. Hence, the skilled artisan would recognize that that the molecular weight will vary.
For the reasons above, the limitations of claims 27, 28, 31-33, and 45 are met.
Claim 29 is directed to a mass ratio of the substance to the liposome carrier as set forth therein.
While Zhang et al does not give all the amounts of the ratio of substance to liposome carrier, the document discloses that substances such as different polymer-modified silicon dioxide surfaces including chitosan, polylysine and hyaluronic acid may be incorporated into the nanostructures (page 11140, abstract).
In addition, it would be obvious to a skilled artisan to optimize the ratio of substance to liposome carrier because the Zhang et al disclose various way of optimizing the components, desired property of interest (e.g., thickness and surface morphology of the membrane). Still, Zhang et al disclose that one can vary the amount of DSPE-PEG2000 (the other component being optimized in the ratio) from 1.5-5 mole percent (page 11143, left and right columns, bridging paragraph). According to MPEP 2144.05, generally differences in things such as concentration (ratios) wherein the prior art discloses evidence indicating that such factor is critical and may be optimized, determining optimum workable ranges by routine experimentation is expected. Thus, it the limitations of claim 29 are rendered obvious.
Claim 30 is directed to the substance as being one of the many listed therein.
As indicated supra, the claim is not clear on whether the substance is an additional component in the claim or optional as based on the claim language, it is possible that the substance is that which is modified. As a result, if the substance is hyaluronic acid, then it is a weakly acidic substance encompassed by claim 30, line 3. Hyaluronic is considered a weak acid because its pKa (acid constant) ranges from 3-4 which is typical for weak acids (see Mero et al, Polymers, 2014, Vol. 6, pages 346-369, especially, page 347, second paragraph). Thus, the claim limitation is met as Zhang et al disclose the use of hyaluronic acid in its delivery system.
For the reasons set forth supra, the pending invention (claims 27-33 and 45) is rendered obvious by Zhang et al.
Conclusion
Claims 27-33 and 45 are rejected and claims 34-44, 46-50, and 55-58 are withdrawn.
Future Correspondences
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
February 4, 2026