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 .
Information Disclosure Statement
The submitted information disclosure statements (IDSs) were filed on 08/07/2023 and 08/15/2023. The submissions is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements is/are being considered by the examiner.
Response to Restriction
Applicants' election with traverse of Group II including claim 13 and new claims 17-24 that depend on claim 13 without traverse in the reply filed on 11/24/2025 is acknowledged. The requirement is proper and is therefore made FINAL. For examining purpose, Claims 13, 17-24 of Group II are examined in this office action.
Status of Application
Applicants' arguments/remarks filed 11/24/2025 are acknowledged. Claims 1-2 and 4-12 are withdrawn. Claims 3 and 14-16 are canceled. Claims 13 and 17-24 are examined on the merits within and are currently pending.
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 13 and 17 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.
Claim 13 is indefinite because
it recites claim limitation of mixing lipids and surfactants at 5000-20,000 RPM lacking critical context, such as volume, shear rate, or equipment geometry, meaning the same RPM could produce totally different nanoparticles in a 10 mL vial versus a 10-liter tank; the RPM (revolutions per minute) used for stirring mixtures of lipids, surfactants, and drugs—commonly in the preparation of lipid nanoparticles (LNPs), solid lipid nanoparticles (SLNs), or nanoemulsions is heavily dependent on the volume of the mixture and the specific excipients used.
it recites claim limitation of homogenization of 2-6 cycles at 500- 1200 bars pressure without the concentration and volume ranges. It fails to inform those skilled in the art about the scope of the invention with reasonable certainty.
Claim 17 is indefinite because it recites the trademark/trade names: “Precirol® and Compritol® 888 ATO”, 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(b) or 35 U.S.C. 112 (pre-AIA ), 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 names is/are used to identify/describe Compritol® 888 ATO is technically known as glyceryl dibehenate or Glycerol Dibehenate and Precirol® (specifically Precirol® ATO 5) is Glyceryl Palmitostearate, accordingly, the identification/description is indefinite.
Appropriate correction(s) is/are required.
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 non-obviousness.
Claims 13 and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Waugh et al. (US 20190105261 A1) in view of Singh et al. (Singh et al., Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. Journal of Ethnopharmacology 123 (2009) 22–26), Hee et al. (Hee et al., Development and factorial design of glyceryl tristearate based solid lipid nanoparticles (SLNs) containing berberine. Rapports De Pharmacie Vol.2 (1), 2016, 199-210) and further in view of Zhang et al. (WO 2014194053 A2), Hwang et al. (US 20230110451 A1).
Claim 13,
Waugh et al. teach the composition may include nanoparticles and the active agent may be encapsulated within nanoparticles or may be ionically associated with nanoparticles. The nanoparticles or microparticles may be lipid nanoparticles. (0160). The active agent may be Extract of Barberry, Extract of Berberis Aquarius, Extract of Berberis Aquifolium, Extract of Berberis Vulg, Extract of Berberis Vulgaris. (0092).
Waugh et al. do not teach Berberis extract is freeze-dried to a powder on a lyophilizer.
Singh et al. teach preparation of root extract that the Berberis aristate root (100 g) was shade dried, powdered, extracted with 200ml of 50% ethanol and kept at 25 ◦C for 24 h with constant shaking (60 rpm) in laboratory shaker. Mixture was filtered and the process was repeated till filtrate became colorless. Berberis aristate extract was all freeze-dried to a powder on a lyophilizer. (pg. 23, left col., 3rd par.).
Waugh et al. and Singh et al. do not teach steps a-c.
Hee et al. teach a solid lipid nanoparticle (SLN)-based system was developed for efficient incorporation and persistent release of Berderine hydrochloride (BH). Berberine hydrochloride is the Zhangn ingredient in the Berberis extract. (Neag et al., Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Frontiers in Pharmacology | www.frontiersin.org 1 Aug. 2018, Vol. 9, Article 557). Barberine.HCl is the salt form of Barberis extract. Berberine hydrochloride and cholesterol was purchased from Himalaya Healthcare, India. (pg. 199, right col., last par.).
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A formulation of these nanoparticle materials by a hot solvent evaporation method. A 3-factor, 2-level Box-Behnken design was used to optimize the process parameters including Triglyceride (A), Tween 20 (B) and Span 40 (C). (Abs), wherein Triglyceride (A) is a lipid, Tween 20 (B) is a surfactant and Span 40 (C) is a cosurfactant. Triglyceride (A) can be glyceryl tristearate (GTS). GTS based nanocarriers were prepared by a hot solvent evaporation method 200 mg of glyceryl tristearate (GTS) were completely dissolved into dichloromethane. The resulting organic solution was added drop wise into 25 mL of an aqueous solution containing tween 20, span 40 and 200 mg of drug Zhangntained under magnetic stirring at 82±1ºC for 2 hours. During the homogenization process, the temperature was Zhangntained around 82°C to guarantee that the lipid material does not solidify. Then, the obtained SLNs were transferred to glass vials and cooled down immediately to room temperature to Zhangntain the stability of SLNs. (pg. 200, left col., 1st par). Tween 20 is a liquid at room temperature. Glyceryl tristearate (tristearin) typically has a melting point between 71°C and 75°C. (https://en.wikipedia.org/wiki/Stearin). Span 40 (sorbitan monopalmitate) has a melting point/range of 45–48°C. (https://www.cdhfinechemical.com/images/product/msds/31_1116636118_Span40-CASNO-26266-57-9-MSDS.pdf).
Waugh et al., Singh et al. and Hee et al. do not teach the rpm speed of stirring.
Zhang et al. teach preparation of lipid nanoparticles comprising lipids, surfactants and Barberry, by stirring vigorously for 2 hours. The resulting emulsion is combined with 4.8 liters of water and centrifuged at 6,000 rpm for 30 minutes. (00267).
Waugh et al., Singh et al., Hee et al. and Zhang et al. do not teach 2-6 cycles of homogenization at 500-1200 bars pressure to obtain the lipid nano-formulation.
Hwang et al. teach a water-dispersible colloidal solution containing liposomes as organic particles was prepared according to the composition described in Table 3. 100% hydrogenated oleoyl-palmitoyl/oleoyl-stearyl phosphatidylcholine mixture (Lipoid S100-3) and cholesterol were dissolved in ethanol under warming to obtain a mixed solution. The mixed solution was introduced to water at 60° C and mixed and agitated with a homogenizer at a speed of 5000 rpm for 5 minutes. Then, a high-pressure homogenizer (1000 bar, 3 cycles) was used to obtain water-dispersible organic nanoparticles. (0157).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to prepare lipid nanoparticle of Berberis extract taught by Waugh et al., by using the freeze-dried Berberis extract, taught by Singh et al., using lipid, surfactant, and cosurfactant with heating the method taught by Hee et al., and varying the stirring speed and time depending on the volume taught by Zhang et al., and varying the homogenization cycles and pressures depending on concentrations, taught by Hwang et al. since they have provide methods to prepare lipid nano particles of freeze-dried Berberis extract.
With regard to claim 17,
Waugh et al. teach the lipids stearic acid and glyceryl monostearate. (0139).
With regard to claim 18,
Waugh et al. teach propylene glycol (0126, 0141, 0143, 0164); polyethylene glycols, polyvinyl alcohol, polyvinylpyrrolidone (0139); polyethylene glycols (0146, 0164); glycerol (0164); monoethyl ether (transcutol) (0164);
With regard to claim 19,
Waugh et al. teach surfactants and cosurfactants: polysorbate, sorbitan esters (spans), poloxamer (0140); bile salts and derivatives; fatty alcohols (e.g. lauryl alcohol, myristyl alcohol, oleyl alcohol) (0164); diethylene glycol monoethyl ether (0166).
With regard to claim 20,
Waugh et al. teach the composition may include liposomes to facilitate delivery. The compositions may include about 0.1 w/v % to about 15 w/v % lipids. (0161). The permeation or penetration enhancers can be present from about 0.1 to about 30.0% w/w depending on the
type of compound. For example, the penetration enhancers can be included in the formulations of embodiments in a total amount by weight of about 0.1 w/w % to about 15 w/w%, and in various embodiments, the penetration enhancers can be included in a total amount of about 2 w/w % to about 12 w/w %. (0161). The permeation or penetration enhancers are surfactants and co-surfactants listed with regard to claim 19 above. (0165). The non-ionizable glycol ethers can be included in the compositions of various embodiments at a concentration of about 0.01 w/w % to about 50 w/w %, about 1 w/w % to about 25 w/w %, about 2 w/w % to about 20 w/w %, about 0.5 w/w % to about 10 w/w %. (0167), which are solubilizing agent listed in the with regard to claim 18 above. In some embodiments, the methods may deliver at least 10% more active agent, at least 15% more active agent, at least 20% more active agent, (0230).
With regard to claim 21,
Singh et al. teach the root (100 g) was shade dried, powdered, extracted with 200ml of 50% ethanol. All filtrates were pooled, solvent evaporated on Rotavapour (Buchi R-114, Switzerland) and freeze dried to a powder on a lyophilizer. (pg. 23, left col., 3rd par.). The freeze-dried Berberis is the ethanol extracted.
With regard to claims 22-24,
Singh et al. teach:
Preparation of root extract: root was collected from Berberis aristata D.C. (BA). The root (100 g) was shade dried, powdered, extracted with 200ml of 50% ethanol and kept at 25◦C for 24 h with constant shaking (60 rpm) in laboratory shaker. Mixture was filtered and the process was repeated till filtrate became colorless. All filtrates were pooled, solvent evaporated on Rotavapour (Buchi R-114, Switzerland) and freeze dried to a powder on a lyophilizer. The yellow-colored powder extract was stored at −20 ◦C until use. (pg. 23, left col., 3rd par.).
Chemical finger print of Berberis aristata root extract: Sample comprising of 0.5µg of reference compounds and 5µg of extract were loaded on precoated plates (5×10 cm) of silica gel
60 of uniform thickness (0.2mm) using automated TLC applicator (Desaga AS30). The thin layer chromatoplate was developed in a UV chamber (CAMAG) using n-propanol:water: formic acid (90:80:0.4) as a mobile phase and observed under UV light in a TLC scanner (CAMAG) with documentation unit. One more HPTLC plate was developed using several concentrations of extract as well as berberine And was subjected to densitometry at 366 nm for quantification
of berberine in BA root extract. (pg. 23, left col., 4th par.).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 13, 17-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18276227 (reference application- US 20240115512 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because they all reciting the methods of preparing lipid nanoparticles of berbamine with similar lipids and surfactants/emulsifiers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGOC-ANH THI NGUYEN whose telephone number is (571)270-0867. The examiner can normally be reached Monday - Friday 8:00 am.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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