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 .
Status of the Claims
Currently, claims 1-20 are pending in the instant application.
Priority
The instant application claims foreign priority to CN2023108827685, filed on 07/19/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/17/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 3-4, 10-11, 16-17 are objected to because of the following informalities: Wording. Each of the indicated claims recites “a weight ratio” (underlined for emphasis). As a weight ratio range has already been established in claim 1, which said claims depend upon, use of the word “the” rather than “a” would be proper for establishing antecedence. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 15-20 rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because they are directed towards a “use” of the composition of claim 1. See MPEP 2173.05(q):
"Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 "). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967), the Board held the following claim to be an improper definition of a process: "The use of a high carbon austenitic iron alloy having a proportion of free carbon as a vehicle brake part subject to stress by sliding friction." In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), the district court held the following claim was definite, but that it was not a proper process claim under 35 U.S.C. 101: "The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid."
Claim Rejections - 35 USC § 112 Sixth Paragraph – Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“applying the honokiol liposome transdermal gel in a preparation of a formulation” in claim 15.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112 – Second Paragraph
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.
Claim 15-20 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 15 is indefinite for reciting the phrase “applying the honokiol liposome transdermal gel in a preparation of a formulation”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim is considered as indefinite because no positive steps have been recited and the “applying” of the transdermal gel to a preparation of a formulation would not be understandable to a person of ordinary skill in the art (see 112(f) claim interpretation section above).
Claims 15-20 are indefinite for being directed to “use” claims. As the claims in question are not directed towards one of the categories of patentable inventions, a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claims (see 101 rejections above).
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 nonobviousness.
Claim(s) 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (International Journal of Pharmaceutics 410 (2011) 169–174) in view of Sheu (US 20170035701 A1) and Zheng (Drug Delivery, 2010; 17(3): 138–144).
Claim 7 recites a method of preparing a composition of claim 1 comprising the following steps:
preparation of honokiol liposome: taking and uniformly mixing phospholipid, cholesterol, polyethylene glycol or pegylated phospholipid, and honokiol, adding organic solvent to fully dissolve, evaporating to remove the organic solvent to obtain a uniform phospholipid film, adding water to the phospholipid film, stirring for 1-1.5 h, homogenizing to obtain a liposome solution; filtering the liposome solution at 2-10°C with a filter of 0.22 µm to obtain the honokiol liposome;
preparation of honokiol liposome transdermal gel: stirring poloxamer with water for 0.5-5 h until fully swollen, then adding the honokiol liposome obtained in step (1) and an additive during stirring, and stirring for 20-40 minutes to obtain the honokiol liposome transdermal gel.
Wang teaches formulation of honokiol liposomes. More specifically, Wang provides a method of formulating PEGylated honokiol liposomes wherein phosphatidylcholine, cholesterol, MPEG2000 DSPE and honokiol in weight ratios of 1.00:0.15:0.24:0.22 are mixed and dissolved in 15mL chloroform/methanol, the resulting mixture being dried to a thin film in a rotary evaporator, then hydrated in a 5% glucose solution by sonication (page 170)1. Wang does not teach the following:
stirring the water and phospholipid mixture for 1-1.5 hours
filtering the liposome solution with a 0.22 um filter
preparation of the poloxamer transdermal carrier
However, it would be obvious to include the above aspects because : 1) stirring is a ubiquitous technique in the art; 2) Sheu teaches the filtering of honokiol liposomes; and 3) Zheng teaches the formulation of poloxamer hydrogels as transdermal carriers for honokiol. Altogether there would be a reasonable expectation of success in formulating an effective transdermal honokiol liposome formulation.
Firstly, with regards to element (i), it is indicated that Wang uses sonication as a means of homogenizing the honokiol liposome mixture during the hydration step. While Wang does not explicitly teach stirring for 1-1.5 hours, stirring is a well-known and ubiquitous technique in the art of pharmaceuticals and chemistry. It would have been obvious and well within the ability of a person of ordinary skill in the art to employ the technique of stirring to the process of Wang, especially when Wang indicates the need for homogenization.
Secondly, Sheu teaches the formation of honokiol liposomes by combining honokiol with lecithin and pluronic p123. In a process similar to that of Wang Sheu describes a process wherein honokiol, lecithin, and pluronic are dissolved in organic solvent, dried to a film, and hydrated with an aqueous solution (specification [0103])2. However, the teachings of Sheu differ from Wang in that Sheu includes a step wherein the rehydrated mixture is filtered through a 0.22 um membrane. Sheu indicates that the filtration step is capable of removing unencapsulated honokiol from the formulation. As the teachings of both Wang and Sheu are directed towards the use of liposomal honokiol, a person of ordinary skill in the art would have found it obvious to include a step wherein unencapsulated honokiol (i.e., a non-target active) is removed from formulation.
Thirdly, Zheng teaches the use and preparation of pluronic F127 (polaxamer 407) as a hydrogel carrier for honokiol liposomes. More specifically, the teachings of Zheng are directed to the formation of honokiol-loaded F127 micelles, which are then incorporated in to a F127 aqueous matrix. The process of Zheng comprises adding propylene glycol (a penetration enhancer) and F127 to a mixture of water and the honokiol micelles at a temperature of 4 degrees C (page 139)3. While Zheng does not explicitly teach stirring, It would have been obvious and well within the ability of a person of ordinary skill in the art to employ the technique of stirring to the process of Zheng, as a homogenous aqueous matrix would be desirable.
In summary, Wang teaches a method of formulating honokiol liposomes comprising phospholipid, cholesterol, PEG, and honokiol, while Sheu teaches the filtration of honokiol liposomes, and Zheng teaches the use of poloxamer hydrogel carriers for honokiol liposomes. It would have been prima facie obvious at the time of invention for a person of ordinary skill in the art to combine the teachings of the aforementioned to arrive at the claimed invention because there would have been a reasonable expectation of success in formulating an effective transdermal formulation comprising honokiol liposomes.
Claim 8 further limits the method of claim 7 wherein the organic solvent in step (1) is selected from any one or a combination of anhydrous ethanol, chloroform, methylene chloride, and methanol.
Wang teaches the use of chloroform and methanol as solvents.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Sheu and Zheng, and further in view of Shriky (Journal of Colloid and Interface Science 565 (2020) 119–130).
Claim 9 further limits the method of claim 8 wherein the poloxamer in step (2) is stirred with water of 2-10C, with a swelling temperature of 2-10C and a swelling time of 24-72 hours.
As iterated previously, the combined teaches of Wang, Sheu, and Zheng obviate the preparation method of claim 8. Furthermore, Zheng indicates the combination of poloxamer and water (5% glucose solution) at 4C. However, none of Wang, Sheu, or Zheng explicitly teach a swelling time of 24-72 hours. However, it would be obvious to implement such a time, because Shriky teaches 24 hour storage of F127 prior to use, and there would be a reasonable expectation of success in creating a viable poloxamer hydrogel for administration.
Shriky teaches the formulation of injectable hydrogels. One such formulation comprises 0.1-35% F127 dissolved in deionized water at a temperature less than 4C; the formulations were then stored for 24 hours before use (page 120)4. Furthermore, Zheng teaches storage at 4C until “further use”. Given that Shriky and Zheng are both directed towards the formulation of poloxamer hydrogels utilizing F127, a person of ordinary skill in the art would found it obvious to allow for an at least 24 hour time period between formulation and use, as there would have been a reasonable expectation that the resulting mixture would be viable and effective for administration.
Claim(s) 10-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Sheu and Zheng.
Claim 10 further limits the method of claim 7 wherein the weight ratio of honokiol liposome to poloxamer is 1:1-1:10.
As iterated in the rejection of claim 7, the combined teachings of Wang, Sheu, and Zheng obviate the method of claim 7. However, none of Wang, Sheu, and Zheng explicitly teach the recited weight ratio of honokiol liposome to poloxamer. However it would be obvious to arrive at such a range per the principle of routine optimization. Zheng conducts an investigation on the effects of honokiol micelle concentration on the sol-gel properties of the F127 hydrogel carrier. Zheng found that increasing the honokiol micelle concentration in formulation led to a decrease in sol-gel transition temperature, as depicted in the following Figure 4 (page 142):
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As the honokiol concentration is result-effective with the physical properties of the F127 hydrogel matrix, a person of ordinary skill in the art would be motivated to optimize the honokiol:poloxamer ratio to arrive at a formulation having a favored or desired transition temperature. See MPEP2144.05(II):
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.).
Claim 11 further limits the method of claim 7 wherein the weight ratio of honokiol liposome to poloxamer is 1:2-1:6.
As iterated in the rejection of claim 7, the combined teachings of Wang, Sheu, and Zheng obviate the method of claim 7. However, none of Wang, Sheu, and Zheng explicitly teach the recited weight ratio of honokiol liposome to poloxamer. However it would be obvious to arrive at such a range per the principle of routine optimization. Zheng conducts an investigation on the effects of honokiol micelle concentration on the sol-gel properties of the F127 hydrogel carrier. Zheng found that increasing the honokiol micelle concentration in formulation led to a decrease in sol-gel transition temperature. As the honokiol concentration is result-effective with the physical properties of the F127 hydrogel matrix, a person of ordinary skill in the art would be motivated to optimize the honokiol:poloxamer ratio to arrive at a formulation having a favored or desired transition temperature. See MPEP2144.05(II).
Claim 12 further limits the method of claim 7 wherein the poloxamer is selected from any one or a combination of poloxamer 407, poloxamer 188, poloxamer 338, poloxamer 237, poloxamer 124, poloxamer 181, poloxamer 182, and poloxamer 331.
Zheng teaches the use of pluronic F127 (poloxamer 407).
Claim 13 further limits the method of claim 7 wherein the poloxamer is poloxamer 407 or poloxamer 188.
Zheng teaches the use of pluronic F127 (poloxamer 407).
Claim 14 further limits the method of claim 7 wherein the additive is selected from any one or a combination of antioxidants, transdermal enhancers, moisturizers, pH adjusters, preservatives, and thickeners.
Zheng teaches the inclusion of propylene glycol as a transdermal penetration enhancer.
Allowable Subject Matter
The prior art does not teach or suggest the composition of claims 1-6. The closest prior art are Wang (previously referenced), Zheng (previously referenced), and Hu (Exp. Mol. Med. Vol. 40(6),617-628, 2008).
Wang teaches compositions comprising liposomal honokiol, wherein the liposomal honokiol is formed from the mixture of phosphatidylcholine, cholesterol, MPEG2000 DSPE and honokiol in weight ratios of 1.00:0.15:0.24:0.22. While the components would constitute a phospholipid, honokiol, cholesterol, and PEG as recited in claim 1, the teachings of Wang provide a different weight ratio for said components. Wang does not provide any alternate component ratios or provide any teachings regarding the alteration of the component ratios. Wang also does not teach the gel poloxamer gel matrix.
Zheng teaches the combination of honokiol micelles (liposomes) with poloxamer hydrogel carrier. Zheng however does not teach liposomes comprising each of phospholipid, honokiol, cholesterol, and PEG. Zheng is silent with regards to liposomes comprising the aforementioned components.
Hu teaches liposomes comprising honokiol Lecithin, cholesterol, PEG4000, and honokiol in a weight ratio of 3:3:6:4. While each of the components would constitute a phospholipid, honokiol, cholesterol, and PEG as recited in claim 1, the teachings of Wang provide a different weight ratio for said components, and do not appear to teach or suggest an alternate weight ratio. Hu also is silent regarding the inclusion of a poloxamer gel matrix.
Conclusion
Claims 1-6 are in condition for allowance.
Claims 7-20 are rejected.
Claims 3-4, 10-11, 16-17 are objected to.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “PEGylated liposomal honokiol was prepared by thin film evaporation-sonication method (Hou et al., 2008) and described briefly as follows: phosphatidylcholine, cholesterol, MPEG2000 DSPE and honokiol in weight ratios of 1.00:0.15:0.24:0.22 were mixed and dissolved in 15mL chloroform/methanol (1:4, v/v) in a round-bottomed flask. The mixture was dried to form a thin film in the rotary evaporation apparatus under vacuum in water bath at 40◦C. The resulting film was left overnight and then hydrated with 5% glucose solution while sonication for 10min. The solution was put into cillin bottles and mixed with cryoprotectant of mannitol. The mixture was freeze-dried in the freeze dryer. Before use, the lyophilized PEGylated liposomal honokiol was directly dissolved in 5% glucose solution for study, with a resulting concentration of honokiol at 4mg/mL.”
2 “Nutraceutical drug honokiol/magnolol was used as the enclosed drug. Referring to the flow diagram of FIG. 2 for preparing a drug nanocarrier and the description of the above embodiments, 6 mg honokiol/magnolol, 6 mg lecithin, and 60 mg Pluronics P123 were first dissolved in organic solvent and the thin film was formed after evaporation of the organic solvent. 30 mg soybean lecithin was suspended in 1.0 mL deionized water and then subjected to ultrasonication for forming a lecithin nanosuspension. Then the lecithin nanosuspension was used to hydrate the thin film containing honokiol/magnolol/lecithin/sodium glycolate and the mixture was subjected to ultrasonication at full power for at least 5 min while maintaining a constant temperature to obtain a solution having a nanocarrier. Uncapsulated drug was discarded by filtering this nanocarrier solution via 0.22 um membrane.”
3 “In this work, 5%(v/v) propylene glycol was added as a transdermal penetration enhancer. Then the calculated amount of F127 was added to drug-loaded or blank micelles solutions at 4°C to form solution (sol), while the total concentration of F127 was maintained at 20% (w/w).The obtained F127 sol was kept at 4°C for further use.”
4 “Pluronic F127 with molecular weight of 12600 g/mol was obtained from Sigma-Aldrich (St. Louis, MO) and used as received. Formulations were prepared according to the cold method by Sch molka [22]. F127 concentrations of 0.1–35% (w/w%) were prepared by dissolving the copolymer in deionized water (18 MX cm) or deuterium oxide (99.8%) at a temperature below 4 C, and left to rest for at least 24 h before performing characterisation.”
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