DETAILED ACTION
Claims 16-19, 21-36 are currently pending. Claims 16-19, 21-26 and 31-36 are currently under examination.
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 .
Withdrawn Rejections
The rejection of claims 18 and 21-25 under 112(b) are withdrawn as Applicant has amended the claims to remove preferable claim language and clarified weight and parts by volume.
Examiner’s Note
Applicant's amendments and arguments filed 01/06/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 01/06/2026, it is noted that claims 16-18, 21-25 are amended and claims 31-36 are newly added. No new matter or claims have been added.
Claim Interpretation:
Claims 32-35 are dependent on claim 21. Claim 21 is directed to at least one feature selected from the group A-F, therefore only requiring a single component of A-F. Newly added claims 32-35 further define A (claim 32), B (claim 33), C (claim 34) and D (claim 34). As each of A-F is not required by claim 21, dependent claims 32-35 additionally only require at least one of A-F. Claims 32-35 simply further define A, B, C and D if their category of ingredient is included.
New Rejections/Objections:
The following rejections are newly applied.
Claim Objections
Claims 23-24 are objected to because of the following informalities: Claim 23-24 contain the limitations of “parts per volume of…, wherein 1 part by weight corresponds to 1 milliliter”. In the response dated 01/06/2026 Applicant stated the claim amendments further defined parts by volume (page 8), therefor clarifying parts by volume by using the term parts by weight multiple times appears to be a typographical error. Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 21 and 25 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 21 and 25 contains the trademarks/trade names Tween 80. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe polyethylene glycol sorbitan monooleate, accordingly, the identification/description is indefinite.
Claim 21 recites “rapamycin derivative”. The term "derivative" in claim 21 is a term which renders the claim indefinite. The term "derivative" is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how structurally different a compound may be any of the claimed compounds and still be considered a derivative of these compounds. The instant claims and specification do not provide a clear metes and bounds of the claim and the term derivative is not defined.
Modified Rejection:
The following rejections are modified based on Applicant’s claim amendments and newly added claims.
Claim(s) 16-19, 21-22, 26 and 31-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0076591 (previously applied) in view of CN111976813 (previously applied) and US 2019/0046693.
Regarding claim 16, the limitation of a drug coating, wherein the drug coating comprises a drug active coating which are sequentially attached to the surface of a substrate is met by the ‘591 publication teaching holes on a stent (abstract). Core-shell particles are taught to be deposited within the indention of a textured stent surface [0052] wherein depositing the core shell particles allow for controlled release over time [0172]. The core-shell particles have several layers of therapeutic agent and the core shell particle to be different therapeutic agents to allow for sequential delivery of different therapeutic agents [0176]. Multiple therapeutic agents may be deposited as layers. A first therapeutic agent is deposited into/onto the coating retainer, then a second therapeutic is deposited into/onto the coating retainer thereby forming two layers of therapeutic agent. Layer may contain the same therapeutic agent but the concentrations in adjacent layer may be different [0078]. The layering of therapeutic agent allows for the elution of the therapeutic agents from the stent in a desired sequence [0080]. The ‘591 publication teaching the particles are between 1nm to 999 nm or 1 to 50 um diameters [0172], thus the core shell particles read on both the core shell particles and the nanoparticles.
Regarding claim 17, the limitation of wherein the drug active coating comprises a core-shell structure and or a drug nanoparticle layer wherein the core shell structure comprises a core-shell structure particle, the core shell structure particle having an inner core and an outer shell surrounding the inner core, the inner core is a drug particle and the outer shell is a polymer shell is met by the ‘591 publication teaching a core comprises a therapeutic agent and a shell comprises a biodegradable material [0173]. The ‘591 publication teaching the particles are between 1nm to 999 nm or 1 to 50 um diameters [0172].
Regarding claims 18-19, 31, the limitation of wherein the core-shell structure particle has a particle size D50 of 100 nm to 9 um, 100 nm to 600 nm is met by ‘591 publication teaching the particles are between 1nm to 999 nm or 1 to 50 um diameters [0172]. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding the limitation of wherein the drug coating comprises a core-shell structure layer, a drug nanoparticle layer which are sequentially attached to the surface of the substrate is met by the core-shell particles have several layers of therapeutic agent and the core shell particle to be different therapeutic agents to allow for sequential delivery of different therapeutic agents [0176]. Multiple therapeutic agents may be deposited as layers. A first therapeutic agent is deposited into/onto the coating retainer, then a second therapeutic is deposited into/onto the coating retainer thereby forming two layers of therapeutic agent. Layer may contain the same therapeutic agent but the concentrations in adjacent layer may be different [0078]. The layering of therapeutic agent allows for the elution of the therapeutic agents form the sent in a desired sequence [0080]. The ‘591 publication teaching the particles are between 1nm to 999 nm or 1 to 50 um diameters [0172]. Thus teaching multiple layers of core-shell containing particles which may be nano sized and are applied sequentially, wherein the amounts of drug in the layers is optimizable parameter to obtain the desired sequence (reading on 21d and 35).
Regarding claim 26, the limitation of a drug-coated balloon comprising a balloon body and a drug coating of claim 16 attached to the outside of the balloon body is met by the ‘591 publication teaching the stents to be mounted on a balloon to be delivered [0007]. Wherein the stent is over the balloon the balloon is indirectly coated with the drug containing coating.
Regarding claim 33, the ‘591 publication teaches the amount of material (therapeutic agent or biodegradable material) forming each section/layer of the core shell particle can be the same or different [0174].
The ‘591 publication does not specifically teach positively charged hydrophobic modified layer comprises a positively charged modified substance and a hydrophobic substance the hydrophobic substance is phytanic acid and the positively-charged modified substance is dioleoyl phosphatidylethanolamine (claim 16).
The ‘591 publication does not specifically teach the core-shell structure layer comprises a binder (claim 21) and wherein the hydrophobic substance is selected from fatty acids, natural phospholipids or synthetic phospholipids (claim 22, 36).
The ‘813 publication teaches rapamycin nanoparticle for porous balloon angioplasty. The rapamycin nanoparticles include polymer core and a phospholipid shell wherein the polymer core is composed of rapamycin and a biodegradable polymer. Different material is used to have slow delivery of poorly soluble drugs in the body and improve affinity for the tissues in diseased areas and can be used in conjunction with a perforated balloon (abstract). The rapamycin nanoparticles are composed of hydrophobic polymer core and a lipophilic phospholipid shell, wherein the hydrophobic polymer core contains rapamycin and a polymer and the particle size is 100 to 500 nm. The phospholipids are taught to be two or more of natural phospholipids and are preferably cationic such as dioleoylphosphatidyethanolamine (claim 1-7). The making of the nanoparticles includes aqueous solution containing a surfactant (claim 8) and the aqueous phase forming the particles include polyvinyl alcohol (Example 2) and the two phospholipids are dissolved in the oil phase (page 2, last paragraph), thus teaching hydrophobic substance.
The ‘693 publication teaches lipophilic matrix and a plurality of micro-reservoirs dispersed in the lipophilic matrix. The plurality of micro-reservoirs comprises an active agent (abstract). The lipophilic matrix is configured to adhere to a luminal surface when the expandable portion is expanded and transfer at least a portion of the plurality of micro-reservoirs to the lumina surface [0009]. The hydrophobic matrix includes at least one of lipids, phospholipids, fats, fatty acids and their derivatives with particularly useful formulations containing a combination of a sterol and a fatty acid or phospholipid. Cholesterol and fatty acids or phospholipids may provide homogenous mixture for coating and result in a homogenous coating on the balloon surface [0027]. Ranges of hydrophobic mixture components are taught to be 1:2 to 3:1 [0028], thus teaching an optimizable range. Preferred fatty acids are taught to include palmitic acid [0028]. Preferred phospholipids are taught to include dioloylphophatidylethanolamine (DOPE [0030]. Rapamycin is taught to be an active agent [0032]. Formulations are taught which includes fatty acid, cholesterol and DOPE-mPEG (Table 5, [0131]-[0145]).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use core-shell particles taught by the ‘813 publication for the core shell particles taught by the ‘591 publication because the ‘813 publication teaches rapamycin nanoparticles to be used on a medical device comprising a core shell structure and the ‘591 publication teaches the use of drug containing core-shell particles on an implantable medical device. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘591 publication and the ‘813 publication are both directed to core-shell particles in the nanometer size range that release active agents from a coating on a medical device wherein the desire is for slow delivery of the active agent.
Wherein multiple layers of the core shell particle are applied sequentially as taught by the ‘591 publication of the particles taught by the ‘813 publication would result in sequential layers of core shell particle, nanoparticle and positively charged hydrophilic modified layer as each layer would contain each and comprising langue allows for all ingredients in each layer.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of DOPE and phytanic acid in the formulation taught by the ‘591 publication and the ‘813 publication as the ‘813 publication teaches the use of DOPE as a shell phospholipid used in balloon angioplasty and the ‘693 publication teaches the use of combinations of fatty acids and phospholipids are known to be used in drug delivery devices to adhere to the vessel wall upon delivery. Therefore one of ordinary skill in the art before the filing date of the claimed invention would be motivated as the combination of hydrophobic substances including DOPE and phytanic acid are taught to have the effect of delivery to the vessel wall and have an expectation of success as the ‘813 publication teaches the use of DOPE in combination with rapamycin particles and the ‘693 publication teaches combinations of fatty acids and phospholipids may be used in combination with rapamycin drug delivery from a medical device.
Claim(s) 23-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0076591 in view of CN111976813 and US 2019/0046693as applied to claims 16-19, 21-22, 26 and 31-34 above, and further in view of CN 110496261.
As mentioned in the above 103(a) rejection, all of the limitations of claims 16-19, 21-22, 26 and 31-36 are taught by the combination of the ‘591 publication, the ‘813 publication and the ‘693 publication.
The ‘813 publication teaches 0.02 g rapamycin, 0.16g polylactic acid, 0.01 g of DPPC, 0.003 g of PEGylated phospholipid and 0.003 g of cationic phospholipid as the oil phase and 1% PVA aqueous solution taken 320 mL of the aqueous phase were used to form the liposomes (Example 2).
The combination of references does not specifically teach wherein the core shells have an amphiphilic polymer at 0.5 to 50 parts by weight (claim 23).
The ‘251 publication teaches cationic nanomedicine characterized in that it includes a carrier and a drug loaded on the carrier wherein the carrier contains one or more of a cationic amphiphilic compound and a cationic modified (claim 1). The cationic amphiphilic compound includes amphiphilic polymer based on thiol modified chitosan (claim 5). The particles are taught for sustained release (claim 8).
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 use an amphiphilic chitosan polymer as taught by the ‘251 publication in the particles taught by the ‘813 publication because the ‘813 publication teaches chitosan polymers to be used to form the core and the ‘251 publication teaches specific amphiphilic chitosan polymers known to form drug delivery particles for sustained release. It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a known chitosan polymer used to form drug delivery particles for the chitosan taught by the ‘813 publication.
As MPEP 2144.05 recites “where 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 optimization”. It would have been obvious to one ordinary skill in the art to optimize the ingredients taught to form the core shell structure to obtain the desired particles as the ‘813 publication teaches the use of certain concentration (page 2, bottom of page) teaching that the concentrations are not required to be specific but optimizable. ‘It is prima facie obvious for a skilled artisan to pursue the known options within his or her own technical grasp to achieve the predictable results of formulating core shell particles to deliver and active agent.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
103: The ‘591 publication (Girton) in view of the ‘813 publication (Wuhu)
Applicant argues the ‘591 publication does not teach the drugs and charged hydrophobic layers are applied sequentially, the drug coating comprises a core-shell structure layer and a drug nanoparticle layer and the hydrophobic substance if phytanic acid and the positively charged modified substance is dioleoyl phosphatidylethanolamine.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant is referred to the modified rejection above wherein the ‘693 publication teaches the combination of DOPE and phytanic acid. Regarding the sequential layering, wherein multiple layers of the core shell particle are applied sequentially as taught by the ‘591 publication of the particles taught by the ‘813 publication would result in sequential layers of core shell particle, nanoparticle and positively charged hydrophilic modified layer as each layer would contain each and comprising langue allows for all ingredients in each layer.
Applicant argues the multilayer drug coating configuration has technical advantages through its unique three-layer architecture including a core shell structure layer, a drug nanoparticle layer and a positively charged hydrophobic modified layer sequentially attached to the substrate surface. This structure is firmly bound to the ballon and has immediate and sustained drug release.
In response, Applicant is arguing limitations not present in the instant claims. Applicant is narrowly arguing a specific core-shell particle structure, nanoparticle structure and positively charged hydrophobic modified layer, wherein the instant claims contain comprising language and do not define the ingredients of the nanoparticles. Thus multiple layers of core shell particles with a shell of the modified hydrophobic layer meet the instant claim limitations as the top layer would contain the positively charged hydrophobic modified layer and the core shell particles of the prior art are nanoparticle sized and thus read on both the core shell particles and the nanoparticles. Applicant has not defined each layer of the claim and uses open claim language of comprising.
Applicant argues the selectin of phytanic acid and phosphatidylethanolamine departs from the ‘591 publication use of fatty acids and stearic acid. The experimental data demonstrated below shows DC cholesterol and stearic acid compared to phytanic acid and dioleoyl phosphatidylethanolamine show superior drug transfer rates. These results demonstrate that the specific special combination provides unexpected synergistic effects that are substantially improved both drug delivery efficiency ad procedural safely. Claim 16 is non-obvious because the recited limitations combine multiple technical features that work synergistically to solve the long-standing problems in drug coated balloon technology. The multi-layer structure addresses drug retention issues while the specific chemical combination provides superior performance characteristics that were either disclosed nor suggested by the cited references.
In response, Applicant is narrowly arguing a specific core-shell particle structure, nanoparticle structure and positively charged hydrophobic modified layer, wherein the instant claims contain comprising language and do not define the ingredients of the nanoparticles. Thus multiple layers of core shell particles with a shell of the modified hydrophobic layer meet the instant claim limitations as the top layer would contain the positively charged hydrophobic modified layer and the core shell particles of the prior art are nanoparticle sized and thus read on both the core shell particles and the nanoparticles. Applicant has not defined each layer of the claim and uses open claim language of comprising. Thus the presented data is not commensurate in scope with the instant claims.
Conclusion
No claims are allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613