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 .
Status of Application
Applicant’s election without traverse of invention II, claims 8-11 in the reply filed on 01/07/2026 is acknowledged.
Claims 1-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/07/2026.
Applicant addition of new claims 12-17 in the reply filed on 01/07/2026 is acknowledged.
Claims 8-17 are under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in South Korea on 27 December, 2022. It is noted, however, that applicant has not filed a certified copy of the Korean Patent Application No. 10-2022-0185355 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed 12 January, 2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein has not been considered.
Drawings
The following drawings are objected to: Figures 1, 2, 3, 5, and 6.
Figures 1 and 6 are objected to because they are blurry and difficult to read. Figure 6 contains two panels which should be individually labelled. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Figures 1, 2, 3, 5, and 6 are objected to as color drawings. Appropriate correction is required.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The use of the term Tween, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term SPAN, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term Pluronic, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 8are objected to because of the following informalities: the use of "microbubble" in line 7 . Appropriate correction is required.
Claim 14 is objected to because of the following informalities: the claim lists the same solvent twice. Dichloromethane and methylene chloride are the same solvent used for the same context and should be listed once. Appropriate correction is required.
Claim 15 is objected to because of the following informalities: chemical names should be lowercase when not starting a sentence. Perfluoro-n-pentane and 1H-Undecafluoropentane should be "perfluoro-n-pentane" and "1H-undecafluoropentane". Appropriate correction is required.
Claim 16 is objected to because of the following informalities: polystyrene-co-maleic anhydride is not a polyethylene glycol-based polymer. Appropriate correction is required.
Claim Interpretation
Claims 8 and 11 recite Tween-type and SPAN-type surfactants. For the purposes of examination, the examiner interprets this to include any sorbitan-containing or sorbitan-like nonionic surfactant. For the purposes of examination, the examiner interprets any art which contains these compounds to read on the Tween-type and SPAN-type surfactants.
Claims 8, 11, and 13 are product-by-process claims. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See MPEP 2113(I). Therefore, the examiner interprets claims 8, 11, and 13 as product-by-process claims and finds that any prior art with the product reads upon these claims regardless of the method of making.
Claim 16 recites Pluronic F-127, polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) and a copolymer of polyethylene oxide and polypropylene oxide. The examiner notes that “a copolymer of polyethylene oxide and polypropylene oxide” is interpreted to include any multiblock copolymer, such as diblock, triblock, or tetrablock, etc, arranged in any alternating order. Accordingly, the polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) is a particular form of “a copolymer of polyethylene oxide and polypropylene oxide where it is a triblock copolymer with PPO in the middle but the lengths of each block are unspecified. Additionally, Pluronic F-127 is a particular form of PEO-PPO-PEO where the lengths of each triblock are specified according to the trademark at the time. Therefore, the examiner will interpret any art discussing copolymers of PEO and PPO as relevant to the claim.
Claim 17 recites, “The drug delivery system of claim 8, wherein the first surfactant and the second surfactant are included in weight ratio of 1:0 through 1:1.” The claim refers to “the” first surfactant and “the” second surfactant of claim 8. Therefore, the examiner interprets this to mean the first surfactant is the PEG based nonionic surfactant and the second surfactant is the “Tween-type surfactant or a SPAN-type surfactant”.
Furthermore, the examiner notes that while claim 17 does not conclude with, “respectively”, to clarify the order of the weight ratio, it is clear that the order of the weight ratio and the order of the surfactants correspond. Therefore, the examiner interprets the weight ratio as being the weight ratio of the first surfactant to the second surfactant.
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 8, 10, 11, and 16 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 8 and 1 contain the trademark/trade names Tween and SPAN. 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 name is used to identify/describe a class of chemical structures and, accordingly, the identification/description is indefinite.
Claim 10 recites the limitation "the system" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 contains the trademark/trade name Pluronic. 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 name is used to identify/describe a class of chemical structures and, accordingly, the identification/description is indefinite.
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.
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 8-12, 15, and 17 is/are rejected under 35 U.S.C. 103 as being obvious over Kontogiannis, O., et al. (Int. J. Mol. Sci. 2022, 23, 13814) in further view of Birla Institute of Technology and Science, et al. (IN202111058586 A) in further view of Unger et al. (US2005/0019266 A1).
Kontogiannis et al. (hereafter referred to as Kontogiannis) is drawn to ultrasound-induced drug delivery system (e.g. title, abstract (lines 2, 4, 8); pg 2, lines 5-8, 25-29; pg 3, lines 1-2; Table 1; pg 13, lines 3-17). Of note, Kontogiannis teaches a method of manufacturing a drug delivery system through a modified thin-film hydration with sonication to form the final drug delivery system (pg 13, lines 1-18).
As to claim 8, Kontogiannis teaches an ultrasound-induced drug delivery system with the required steps: dissolving components in organic solvent (pg 13, lines 4-8), manufacturing a concentrate by removing an organic solvent (pg 13, lines 9-11), and manufacturing the final system using a sonicator after putting liquid into the manufactured concentrate (pg 13, lines 12-17). Kontogiannis teaches that drugs and dyes may be used with PEG-, Tween-, or SPAN-based surfactants (pg 2, lines 14, 21, 32).
Kontogiannis does not teach dissolving drugs or dyes with the non-ionic surfactants.
Kontogiannis does not teach the use of liquid gas.
Birla Institute of Technology and Science, et al. (hereafter referred to as Birla) is also drawn to drug delivery system composed of nonionic surfactants (e.g. title; abstract, lines 4-7; and specification: pg 2, lines 8; pg 3, line 4; pg 13, line 18) with fat-soluble dyes (e.g. pg 9, lines 1-4, pg 21, lines 1-7, 9-11, and pg 23, line 3). The works of Kontogiannis and Birla are drawn to same field of endeavor as the claimed invention. Therefore, a person of ordinary skill in the art would be motivated to combine elements from Kontogiannis and Birla.
Regarding dissolving drugs or dyes with the non-ionic surfactants of claim 8, Kontogiannis teaches preparing a solution of PEG-based nonionic surfactant, Poloxamer 188, and a nonionic surfactant, such as Tween 80® or Span 60®) in an organic solvent (pg 13, lines 4-8).
Kontogiannis does not teach dissolving drugs or dyes with the non-ionic surfactants.
Birla teaches that the drug delivery system may have a fat-soluble compound (such as a drug) dissolved with the non-ionic surfactant in the organic solvent (pg 21, lines 1-11). The known technique in Birla may be combined with the known work of Kontogiannis given that both Kontogiannis and Birla are drawn to drug delivery systems using PEG-type, Tween-, and SPAN-type non-ionic surfactants. Birla’s inclusion of the fat-soluble drug with the non-ionic surfactants is done in the same way as the claimed invention. Therefore, a person of ordinary skill in the art could have applied the known “improvement” of dissolving fat-soluble drugs at the same time as the non-ionic surfactants in Birla to the method of manufacturing a drug delivery method in Kontogiannis and the results would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(C).
Regarding concentration through removal of organic solvent of claim 8, Kontogiannis teaches concentration until removal of the organic solvent (pg 13, lines 9-11).
Regarding microbubble manufacture through sonication after adding a liquid gas into concentrate of claim 8, Kontogiannis teaches sonication after adding a liquid into concentrate (pg 13, lines 12-17).
Kontogiannis does not teach the use of liquid gas.
Unger et al. (hereafter referred to as Unger) is also drawn to microbubble drug delivery systems (abstract, para [0031], para [0033], and para [0051]). Unger teaches microbubbles (pg 5, para [0051], lines 1-3) composed of lipids or non-ionic polymer surfactants (pg 16, para [0121], lines 1-5) that are gas-filled (pg 5, para [0057], lines 1-3). Unger teaches the use of liquid gases (pg 16, para [0123]; and pg 17, para [0124], lines 6-9; para [0130], lines 6-9). Kontogiannis and Unger teach drug delivery systems made from small-molecule surfactants and nonionic polymer surfactants. And, a simple substitution of the liquid gas of Unger could be made for the liquid of Kontogiannis. The substituted liquid gas of Unger and liquid of Kontogiannis and functions are known in the art. Therefore, a person of ordinary skill in the art could have substituted the known liquid gas of Unger for the the liquid of Kontogiannis and the results of the substitution would have been predictable. See MPEP 2143 (I)(B).
The prior art included each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference, one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. Therefore, one of ordinary skill in the art would have recognized that the results of the combination were predictable. See MPEP 2143(I)(A). Given that Kontogiannis, Birla, and Unger are all drawn to non-ionic surfactant-based drug delivery systems, a person having ordinary skill in the art would be motivated to combine the teaching in Kontogiannis with the teaching of Birla and Unger to get the full embodiment of claim 1.
As to claim 9, Unger teaches the use of increased drug release by ultrasonic irradiation (pg 30, para [0226], lines 7-14).
As to claim 10, Birla teaches the use of fat-soluble drugs (pg 3, line 8; pg 7, lines 5-6).
As to claim 11, Kontogiannis teaches an ultrasound-induced drug delivery system with the required steps: dissolving components in organic solvent (pg 13, lines 4-8), manufacturing a concentrate by removing an organic solvent (pg 13, lines 9-11), and manufacturing the final system using a sonicator after putting liquid into the manufactured concentrate (pg 13, lines 12-17). Kontogiannis teaches that drugs and dyes may be used with PEG-, Tween-, or SPAN-based surfactants (pg 2, lines 14, 21, 32).
Kontogiannis does not teach dissolving drugs or dyes with the non-ionic surfactants.
Kontogiannis does not teach the use of liquid gas.
Kontogiannis does not teach the use of non-ionic surfactant polymer microbubbles for use as contast medium.
Regarding dissolving drugs or dyes with the non-ionic surfactants of claim 11, Kontogiannis teaches preparing a solution of PEG-based nonionic surfactant, Poloxamer 188, and a nonionic surfactant, such as Tween 80® or Span 60®) in an organic solvent (pg 13, lines 4-8).
Kontogiannis does not teach dissolving drugs or dyes with the non-ionic surfactants.
Birla Institute of Technology and Science, et al. (hereafter referred to as Birla) is also drawn to drug delivery system composed of nonionic surfactants (e.g. title; abstract, lines 4-7; and specification: pg 2, lines 8; pg 3, line 4; pg 13, line 18) with fat-soluble dyes (e.g. pg 9, lines 1-4, pg 21, lines 1-7, 9-11, and pg 23, line 3).
Birla teaches that the drug delivery system may have a fat-soluble compound (such as a drug) dissolved with the non-ionic surfactant in the organic solvent (pg 21, lines 1-11). The known technique in Birla may be combined with the known work of Kontogiannis given that both Kontogiannis and Birla are drawn to drug delivery systems using PEG-type, Tween-, and SPAN-type non-ionic surfactants. Birla’s inclusion of the fat-soluble drug with the non-ionic surfactants is done in the same way as the claimed invention. Therefore, a person of ordinary skill in the art could have applied the known “improvement” of dissolving fat-soluble drugs at the same time as the non-ionic surfactants in Birla to the method of manufacturing a drug delivery method in Kontogiannis and the results would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(C).
Regarding concentration through removal of organic solvent of claim 11, Kontogiannis teaches concentration until removal of the organic solvent (pg 13, lines 9-11).
Regarding microbubble manufacture through sonication after adding a liquid gas into concentrate of claim 11, Kontogiannis teaches sonication after adding a liquid into concentrate (pg 13, lines 12-17).
Kontogiannis does not teach the use of liquid gas.
Unger et al. (hereafter referred to as Unger) is also drawn to microbubble drug delivery systems (abstract, para [0031], para [0033], and para [0051]). Unger teaches microbubbles (pg 5, para [0051], lines 1-3) composed of lipids or non-ionic polymer surfactants (pg 16, para [0121], lines 1-5) that are gas-filled (pg 5, para [0057], lines 1-3). Unger teaches the use of liquid gases (pg 16, para [0123]; and pg 17, para [0124], lines 6-9; para [0130], lines 6-9). Kontogiannis and Unger teach drug delivery systems made from small-molecule surfactants and nonionic polymer surfactants. And, a simple substitution of the liquid gas of Unger could be made for the liquid of Kontogiannis. The substituted liquid gas of Unger and liquid of Kontogiannis and functions are known in the art. Therefore, a person of ordinary skill in the art could have substituted the known liquid gas of Unger for the liquid of Kontogiannis and the results of the substitution would have been predictable. See MPEP 2143 (I)(B).
Regarding use of non-ionic surfactant polymer microbubbles for use in a contrast medium, Kontogiannis teaches a drug delivery system for use in delivery of drugs (pg 2, line 14 and 21).
Kontogiannis does not teach a contrast medium comprising the drug delivery system.
Unger teaches the use of non-ionic surfactant polymer microbubbles for use as contrast medium (pg 39, para [0327], lines 5-7). Since both Kontogiannis and Unger are drawn to drug delivery systems from non-ionic surfactants, a person having ordinary skill in the art would be motivated to combine them to achieve a microbubble delivery system capable of use in a contrast medium.
The prior art included each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference, one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. Therefore, one of ordinary skill in the art would have recognized that the results of the combination were predictable. See MPEP 2143(I)(A). Given that Kontogiannis, Birla, and Unger are all drawn to non-ionic surfactant-based drug delivery systems, a person having ordinary skill in the art would be motivated to combine the teaching in Kontogiannis with the teaching of Birla and Unger to get the full embodiment of claim 11.
As to claim 12, Unger teaches microbubbles with a size range of about 30nm to 100 µm (pg 19, para [0141], lines 4-6. The claimed microbubble size of 0.5-30 µm which falls within the prior art range in Unger. “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)”. See MPEP 2144.05(I).
As to claim 15, Unger teaches perfluoro-n-pentane (pg 45, claim 16).
Unger does not teach 1H-undecafluoropentane or 2H, 3H-perfluoropentane.
Unger teaches liquid gases comprising a fluorinated compound (pg 45, claim 14). And, Unger teaches motivation to use the more stable fluorocarbons that are not completely fluorinated for use in microbubble drug delivery systems (pg 18, para [0133], lines 1-5). Unger teaches partially fluorinated fluoropropanes (pg 18, para [0133], lines 3-5).
Given that Unger teaches a motivation of improved stability for partially fluorinated fluorocarbons, a person of ordinary skill in the art would have been motivated to combine Unger’s teaching of partially fluorinated fluoropropanes with fluoropentanes to arrive at the claimed invention.
The known work of Unger in the field of gas-filled microbubbles for drug delivery and in contrast mediums, may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill. The scope and content of Unger is drawn to microbubble drug delivery systems and contrast mediums. And, Unger teaches the design incentive of improved stability of partially fluorinated fluorocarbons for improved microbubbles which would have prompted adaptation of the known perfluoropentanes. The difference between the claimed invention and the prior art were encompassed in known variations in a principle known in the prior art. Therefore, a person of ordinary skill in the art, in view of the identified design incentives, could have implemented the claimed variation of the prior art, and the claimed variation would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(F).
As to claim 17, Kontogiannis teaches weight ratios from 100:0, 90:10, 80:20, and 50:50 for the first PEG-based nonionic surfactant and the second Tween-type surfactant. This range overlaps the claimed range of 1:0 through 1:1. “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)”. See MPEP 2144.05(I).
Claims 13-14 is/are rejected under 35 U.S.C. 103 as being obvious over Kontogiannis, et al. (Int. J. Mol. Sci. 2022, 23, 13814) in further view of Birla Institute of Technology and Science, et al. (IN202111058586 A) in further view of Unger et al. (US2005/0019266 A1) in further view of Park (US 2021/0259953 A1).
The combined teachings of Kontogiannis, Birla, and Unger, as applied in the above rejections, are incorporated in this rejection. However, the combined teachings of Kontogiannis, Birla, and Unger do not expressly teach dispersion in emulsion-form aqueous solutions, and a specific range of organic solvents which may be used.
Park et al. (hereafter referred to as Park) is drawn to an ultrasound-induced drug delivery microbubble as of title, abstract, specification, and claims.
As to claim 13, Park teaches the dispersion of microbubble drug delivery systems into an emulsion-form aqueous solution (pg 1, para [0016], lines 1-3; and pg 7, claims 3 and 10).
The prior art of Kontogiannis, Birla, and Unger are drawn to drug delivery systems made from non-ionic surfactants and Park is also drawn to an ultrasound-induced drug delivery system. The prior art of Kontogiannis, Birla, and Unger along with Park included each element claimed, though not in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. And, a person of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. Therefore, a person of ordinary skill in the art would have recognized that the results of the combination were predictable. See MPEP 2143(I)(A).
As to claim 14, Kontogiannis teaches an organic solvent, chloroform, to be used in the dissolution of the non-ionic surfactants.
Kontogiannis is silent as to other organic solvents that might be used.
Park teaches any organic solvent having a high drug solubility, (pg 2, para [0022], lines 1-3), with a suitably low boiling point to be removed upon using a vacuum or rotary concentrator (pg 2, para [0023], lines 3-6). Additionally, Park teaches a list of organic solvents, “dichloromethane, ethyl acetate, acetone, ethanol, methanol, methyl ethyl ketone, methylene chloride, dichloroethane, chloroform, dioxane, dimethyl sulfoxide, acetonitrile, acetic acid, or the like.” (pg 2, para [0022], lines 3-7).
Given the teachings of Kontogiannis and Park, a person having ordinary skill in the art could have substituted one known organic solvent for another, and the results of the substitution would have been predictable. In such cases, when swapping similar features that serve the same purpose, it is found to be obvious. See MPEP 2143(I)(B).
Claims 16 is/are rejected under 35 U.S.C. 103 as being obvious over Kontogiannis, et al. (Int. J. Mol. Sci. 2022, 23, 13814) in further view of Birla Institute of Technology and Science, et al. (IN202111058586 A) in further view of Unger et al. (US 2005/0019266 A1) in further view of Park (US 2021/0259953 A1) in further view of Quay (US 2003/0032879 A1) in further view of Soane et al. (US 2001/0044477 A1).
The combined teachings of Kontogiannis, Birla, Unger, and Park, as applied in the above rejections, are incorporated in this rejection. However, the combined teachings of Kontogiannis, Birla, Unger, and Park do not expressly teach the full list of nonionic surfactants listed.
Unger teaches PEG-based nonionic surfactants (pg 21, para [0151]) and copolymers of polyethylene oxide and polypropylene oxide generally as of “poloxamer” (pg 22, para [0158], line 24).
Kontogiannis, Birla, Unger, and Park do not expressly teach Pluronic F-127.
Kontogiannis, Birla, Unger, and Park do not teach polystyrene-co-maleic anhydride.
Kontogiannis, Birla, Unger, and Park do not teach PEG-PLLA-PEG.
Regarding Pluronic F-127, Quay (US 2003/0032879 A1, hereafter referred to as Quay) is drawn to ultrasound-induced microbubbles composed of non-ionic surfactants as of title, abstract, specification and claims. Quay teaches the use of poloxamer 407 which is Pluronic F-127 (pg 6, para [0054], line 6).
The prior art of Kontogiannis, Birla, Unger, and Park taught polymeric drug delivery systems made from a variety of polymers, including poloxamers. Quay teaches poloxamer 407 which is Pluronic F-127. They differ from the claimed device by the substitution of Pluronic F-127 with other poloxamers. The substituted components and their functions were known in the art. Therefore, a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. See MPEP 2143(I)(B).
Regarding polystyrene-co-maleic anhydride, the combined teachings of Kontogiannis, Birla, Unger, Park, and Quay teach non-ionic surfactant drug delivery systems containing nonionic polymers. Unger also teaches non-PEG-based non-ionic polymer surfactants (pg 38, para [0319] and Unger teaches thermoplastic polystyrene-based polymers (pg 38, para [0319], line 8).
The combined teachings of Kontogiannis, Birla, Unger, Park, and Quay do not teach polystyrene-co-maleic anhydride.
Soane et al. (hereafter referred to as Soane) is drawn to polymeric microballoons (or microbubbles) as of title, specifications, and claims. Soane teaches polystyrene-co-maleic anhydride for use in polymeric microbubbles (pg 7, para [0058], line 12).
The prior art of Kontogiannis, Birla, Unger, Park, and Quay all contained non-ionic polymeric drug delivery systems. Unger especially taught polystyrene-based polymers for use in microbubbles. The prior art differed from the claimed microbubble by the substitution of some components (polystyrene-co-maleic anhydride copolymer) with other components. The substituted component and its function was known in the art (e.g. Quay). Therefore, a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. See MPEP 2143(I)(B).
Regarding PEG-PLLA-PEG, the combined teachings of Kontogiannis, Birla, Unger, Park, Quay, and Soane teach non-ionic polymeric drug delivery systems consisting of triblock copolymers. Particularly, Kontogiannis teaches PEG-based triblock copolymers (pg 2, lines 25-29); and, Unger teaches copolymers made from lactic acid and ethylene oxide (pg 16, para [0121], lines 47-54).
The teachings of Kontogiannis and Unger do not explicitly teach the triblock copolymer PEG-PLLA-PEG.
Combination of prior art elements from Kontogiannis and Unger according to known methods may predictably yield the triblock copolymer, PEG-PLLA-PEG, as a non-ionic polymer surfactant for drug delivery. The prior art included each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual explicit combination of the elements in a single prior art reference. And a person of ordinary skill in the art could have combined the monomers listed in Unger with the triblock design recommendations of Kontogiannis as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. Therefore, a person having ordinary skill in the art would have recognized that the results of the combination were predictable. See MPEP 2143(I)(A).
Non-Statutory 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.
Issued Patent No. 11,890,370
Claims 8-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of issued patent No. 11,890,370 in view of Kontogiannis; Birla; Unger; Quay and Soane.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Instant claims 8-17 are taught by conflicting claims in issued patent application No. 11,890,370 claims 1 and 2.
Instant claim 1 is drawn to a method of manufacturing an ultrasound-induced microbubble drug delivery system by dissolving drugs and/or dye and a PEG-based nonionic surfactant and a Tween-type or SPAN-type surfactant in an organic solvent; removing the organic solvent; and adding a liquid gas and then sonicating to manufacture microbubbles.
Conflicting claim 1 teaches a method of manufacturing a microbubble drug delivery system by dissolving drug in an organic solvent, removing organic solvent, and creating nanobubbles, then mixing with surfactant to create the final microbubbles. Conflicting claim 1 does not teach the surfactant dissolved at the same time nor the liquid gas incorporated through sonication. Nevertheless, as noted in the current rejections above, the combined teachings of Kontogiannis, Birla, Unger, Quay, and Soane above render obvious claim 1.
However, the claims of 11,890,370 do not expressly teach the method of manufacturing microbubbles of claim 1, drug release increase by ultrasonic irradiation of claim 9, the fat-soluble drugs of claim 10, contrast medium of claim 11, microbubble size of 0.5-30 µm of claim 12, dispersion in an emulsion-form aqueous solution of claim 13, and organic solvents of claim 14.
As noted in the current rejections above, the combined teachings of Kontogiannis, Birla, and Unger render obvious claim 2-15 and 17. The combined teachings of Kontogiannis, Birla, Unger, and Soane render obvious claim 16.
As claim 1 of issued patent application No. 11,890,370 and the teachings of Kontogiannis, Birla, Unger, and Soane all teach microbubble and polymer vesicles, it would have been obvious to combine claim 1 of issued patent application No. 11,890,370 with Kontogiannis, Birla, Unger, and Soane because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the claimed ultrasound-induced microbubble drug delivery system.
Conclusion
No claim is allowed.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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