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 .
Summary
Claims 1-19 are pending in this office action. Claim 20 is cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on August 2, 2024 is a continuation of a 371 of PCT/KR2023/001265 filed January 27, 2024. The current application claims foreign priority to KR10-2022-0084369 and KR10-2022-0014733 filed July 8, 2022 and February 4, 2022.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on August 2, 2024 is acknowledged. A signed copy of the document is attached to this office action.
Claim Objections
Claims 8 and 16 are objected to because of the following informality:
Claim 8 and 16: Please make the text “Tween” lowercase.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 2 and 8 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 2 and 8 contains the following trademark/trade names:
(Claim 2) IRDye 800CW, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, Alexa Fluor 780, Flamma 749, Flamma 774, Flamma 800, FSD FluorTM 647, FSD FluorTM 680, FSD FluorTM 750, FSD FluorTM 800, Cy5, Cy5.5, Cy7, and Cy7.5
(Claim 8) Labrafil and Labrasol
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 either dyes or surfactants and, accordingly, the identification/description is indefinite.
Also, please delete and amend these trademark/trade names in the specification.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
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 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al. (Magnetic Resonance in Medicine, 2014) in view of DeDora et al. (J. of Biomedical Materials Research B: Biomaterials, 2015), Ito et al. (WO2012/026608A1), Ingber et al. (WO2012/074588A2), Magin et al. (WO2019/136453A1), and Shults et al. (US7,860,545B2).
[The Examiner is going to introduce each reference and then combine them in the rejection of the instant claims.]
1. Hwang et al.
Hwang et al. is considered the closest prior art to the present invention as it teaches in vivo imaging of islet transplantation using PLGA nanoparticles containing iron oxide and indocyanine green (see title). Also, Hwang et al. disclose the following abstract:
Purpose: We determined whether poly(lactic-co-glycolic acid) nanoparticles would be a useful reagent for the successful monitoring of isolated islets by magnetic resonance imaging and optical imaging systems, without clinically relevant toxicity in vitro or in vivo.
Methods: We used iron oxide for MR imaging and a cyanide dye approved by the Food and Drug Administration (indocyanine green) for optical imaging and estimated the in vivo detection of transplanted pancreatic islets.
Results: The poly(lactic-co-glycolic acid) nanoparticles were associated with the islets in vitro and were successfully detected by 4.7 T (MR) and optical imaging, without other toxic effects. When labeled islets were transplanted under the mouse kidney capsule, in vivo T2/ T”2-weighted scans with 4.7 T MR detected as few as 300 labeled islets by 4 weeks. Optical in vivo imaging revealed indocyanine green fluorescence by 2 and 4 days after transplantation of islets containing 250 and 500 µg/mL poly(lactic-co-glycolic acid) nanoparticles, respectively. These results were further supported by the immunohistochemical results for insulin and iron in the recipient mouse kidney and pancreas.
Conclusions: Taken together, these data indicate that poly(lactic-co-glycolic acid) nanoparticles may be used to label transplanted islets and may be imaged with in vivo MR and optical imaging systems (see abstract).
2. DeDora et al.
DeDora et al. teach sulfobutyl ether b-cyclodextrin (Captisol®) and methyl b-cyclodextrin enhance and stabilize fluorescence of aqueous indocyanine green (see title). Additionally, DeDora et al. disclose as the only FDA-approved near-infrared fluorophore, indocyanine green (ICG) is commonly used to image vasculature in vivo. ICG degrades rapidly in solution, which limits its usefulness in certain applications, including time-sensitive surgical procedures. We propose formulations that address this shortcoming via complexation with β-cyclodextrin derivatives (β-CyD), which are known to create stabilizing inclusion complexes with hydrophobic molecules. Here, we complexed ICG with highly soluble methyl β-CyD and FDA-approved sulfobutyl ether β-CyD (Captisol®) in aqueous solution. We measured the fluorescence of the complexes over 24 h. We found that both CyD+ICG complexes exhibit sustained fluorescence increases of >2.0× versus ICG in water and >20.0× in PBS. Using transmission electron microscopy, we found evidence of reduced aggregation in complexes versus ICG alone. We thus conclude that this reduction in aggregation helps mitigate fluorescence autoquenching of CyD+ICG complexes compared in ICG alone. We also found that while ICG complexed with methyl β-CyD severely reduced the viability of MRC-5 fibroblasts, ICG complexed with sulfobutyl ether β-CyD had no effect on viability. These results represent an important first step toward enhancing the utility of aqueous ICG by reducing aggregation-dependent fluorescence degradation (see abstract).
3. Ito et al.
Ito et al. teach polymeric particle and hydrophilic dye having a sulfonate group encapsulated within the particle (see title). In addition, Ito et al. disclose that there is provided an ICG-loaded polymer nanoparticle that is dynamically stable, prevents the leakage of contained ICG and the resulting discoloration, and has a high molar absorbance coefficient. The particle contains a hydrophilic dye having a sulfonate group and a hydrophobic polymer, and the particle further contains at least one of a lipid having a positively charged region, a nicotinic acid derivative and a thiamine derivative (see abstract).
4. Ingber et al.
Ingber et al. teach shear-controlled release for stenotic lesions and thrombolytic therapies (see title). Also, Ingber et al. disclose that the invention provides compositions and methods for treating or imaging stenosis, stenotic lesions, occluded lumens, embolic phenomena or thrombotic disorders. The invention further provides compositions and methods for treating internal hemorrhage (see abstract).
5. Magin et al.
Magin et al. teach 3D in vitro models of lung tissue (see title). Furthermore, Magin et al. disclose that the invention relates to the discovery of tissue mimicking constructs and compositions that can be used to study the growth and development of cells in vitro. In certain embodiments, the invention provides methods of culturing cells on the tissue mimicking polymer microspheres. In other embodiments, the invention provides methods of treating a disease or disorder using the compositions and constructs of the invention (see abstract).
6. Shults et al.
Shults et al. teach analyte measuring device (see title). Additionally, Shults et al. disclose an implantable analyte-measuring device including a membrane adapted to promote vascularization and/or interfere with barrier cell layer formation. The membrane includes any combination of materials, architecture, and bioactive agents that facilitate analyte transport to provide long-term in vivo performance of the implantable analyte-measuring device (see abstract).
Combination of Hwang et al. and DeDora et al.
Regarding instant claim 1, Hwang et al. and DeDora et al. teach near-infrared fluorescent dye-loaded polymer microspheres. The necessary citations within Hwang et al. and DeDora et al. that correspond to instant claim 1 are compiled within Table I.
Table I
Instant Claim 1
Hwang et al. and DeDora et al. Citations
Near-infrared fluorescent dye-loaded polymer microspheres comprising polymer microspheres comprising a polymer; and a near-infrared fluorescent dye complexed with at least one selected from the group consisting of human serum albumin and cyclodextrin.
Hwang et al. disclose a method for preparing a polymer microsphere for labelling a lesion, which is a polymer PLGA microsphere in which indocyanine green (ICG) is loaded as a near-infrared fluorescent dye for labelling a lesion, the method comprising a step in which the near-infrared fluorescent dye forms a complex of human serum albumin, and the complex is loaded into a polymer microsphere (see the abstract, page 1055 and figures 1-6 within Hwang et al.).
Hwang et al. differs from the present invention in that a near-infrared fluorescent dye forms a complex with a cyclodextrin, but the difference amounts to a matter which could be readily selected and applied by a person skilled in the art in view of the feature of DeDora et al. wherein a complex of a near-infrared fluorophore (ICG) and a cyclodextrin increases the fluorescence stability of the fluorophore (see the abstract, page 1458 and figures 1-4 within DeDora et al.), and the effects thus achieved could also be predicted.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Hwang et al. and DeDora et al. prior to the effective filing date of the claimed invention. DeDora et al. disclose a complex of a near-infrared fluorophore (ICG) and a cyclodextrin that increases the fluorescence stability of the fluorophore. This limitation could be added to the disclosure of Hwang et al. under routine experimentation. The motivation to combine the two references would be to create near-infrared fluorescent dye-loaded polymer microspheres comprising polymer microspheres comprising a polymer; and a near-infrared fluorescent dye complexed with at least one selected from the group consisting of human serum albumin and cyclodextrin for marking lesions.
Regarding instant claim 2, Hwang et al. and DeDora et al. teach wherein the near-infrared fluorescent dye is indocyanine green.
Hwang et al. disclose the use of indocyanine green (ICG) as part of the near-infrared complex (see page 1056, RESULTS Synthesis and Characterization of PLGA Nanoparticles; within Hwang et al.).
Regarding instant claim 3, Hwang et al. and DeDora et al. teach wherein the polymer is at least one selected from the group consisting of poly(lactide-co-glycolide) (PLGA), poly(DL-lactide-co-glycolide) (PDLGA), poly(glycolic acid) (PGA), poly(lactide) (PLA), poly(hydroxybutyrate), polycaprolactone (PCL), polydioxanone (PDO), poly(amino acid), polyanhydride, polyorthoester and polyphosphazene.
Hwang et al. disclose the use of the polymer PLGA as part of the near-infrared complex (see page 1056, RESULTS Synthesis and Characterization of PLGA Nanoparticles; within Hwang et al.).
Combination of Hwang et al., DeDora et al., and Magin et al.
Regarding instant claim 4, Hwang et al., DeDora et al., and Magin et al. teach wherein the polymer microspheres comprise a block copolymer of the polymer and poly(ethylene oxide) (PEG).
Hwang et al. disclose the use of the copolymer PLGA (see instant claim 3). Magin et al. is in the art of polymeric microspheres (see abstract; claim 69; page 9, lines 9-12 within Magin et al.). Furthermore, Magin et al. disclose PEG block copolymers such as PEG-PCL, PEG-TMC, PEG-PGS, or PLA-DX-PEG (see page 5, paragraph 3 within Magin et al.). Therefore, a skilled artisan (POSITA; person of ordinary skill in the art) would substitute the copolymers of Magin et al. for the PLGA copolymer of Hwang et al.
Combination of Hwang et al., DeDora et al., and Shults et al.
Regarding instant claim 5, Hwang et al., DeDora et al., and Shults et al. teach wherein the polymer is at least one selected from the group consisting of poly(methyl methacrylate) (PMMA) and polycarbonate (PC).
Hwang et al. disclose the use of the copolymer PLGA (see instant claim 3). Shults et al. is in the art of polymeric microspheres (see column 32, lines 33-40). Additionally, Shults et al. disclose the use of the polymer PMMA (see column 24, line 53 within Shults et al.). Therefore, a skilled artisan (POSITA) would substitute the polymer of Shults et al. for the PLGA copolymer of Hwang et al. under routine experimental conditions.
Combination of Hwang et al., DeDora et al., and Ingber et al.
Regarding instant claim 6, Hwang et al., DeDora et al., and Ingber et al. teach further comprising at least one selected from the group consisting of alginic acid and hyaluronic acid.
Ingber et al. is in the art of polymeric microspheres (see paragraphs [0052-0053] within Ingber et al.). In addition, Ingber et al. disclose the use of alginic acid as an example of a pharmaceutically acceptable carrier (see paragraph [00197] within Ingber et al.). Thus, a skilled artisan (POSITA) would use the alginic acid of Ingber et al. with the disclosure of Hwang et al. under routine experimental conditions.
Combination of Hwang et al., DeDora et al., and Ito et al.
Regarding instant claims 7-8 and 16, Hwang et al., DeDora et al., and Ito et al. teach further comprising a surfactant.
Ito et al. is in the art of using a polymeric particle and hydrophilic dye (see title and abstract within Ito et al.). Also, Ito et al. disclose using polyvinyl alcohol (PVA) as a surfactant (see paragraph [0006] within Ito et al.). Therefore, a skilled artisan (POSITA) would use the surfactant PVA of Ito et al. with the disclosure of Hwang et al. under routine experimental conditions.
Combination of Hwang et al., DeDora et al., and Ingber et al.
Regarding instant claim 9, Hwang et al., DeDora et al., and Ingber et al. teach wherein the polymer microspheres comprise one or more cavities within the polymer microspheres, and the complex is loaded into the cavities.
Ingber et al. disclose perflubutane polymer microspheres are made by creating an emulsion containing PLGA (polylactic-co-glycolic acid), a phospholipid and a pore-forming agent (see paragraph [0052] within Ingber et al.). In this manner, pores or cavities are formed on the microspheres, and allow for material to be loaded into them. Thus, a skilled artisan (POSITA) would use the microspheres having cavities or pores of Ingber et al. with the disclosure of Hwang et al. under routine experimental conditions.
Combination of Hwang et al. and DeDora et al.
Regarding instant claim 10, Hwang et al. and DeDora et al. teach wherein the coating is configured to be disposed on a surface of a metal or non-metallic material.
Hwang et al. disclose wherein the microspheres are for coating is configured to be disposed on a surface of a metal material [(Transmission electron microscopy showed that the iron oxide was localized within the interior of the PLGA Nanoparticles (see Fig. 1a, insert within Hwang et al.) see page 1056, RESULTS Synthesis and Characterization of PLGA Nanoparticles; within Hwang et al.).
Combination of Hwang et al., DeDora et al., and Ingber et al.
Regarding instant claim 11, Hwang et al., DeDora et al., and Ingber et al. teach further comprising at least one selected from an adhesive and a rubber.
Ingber et al. disclose examples of rubber as a sealing material (see paragraph [00224] within Ingber et al.). Therefore, a skilled artisan (POSITA) would use the sealing material, rubber, of Ingber et al. with the disclosure of Hwang et al. under routine experimental conditions.
Combination of Hwang et al. and DeDora et al.
Regarding instant claim 12, Hwang et al. and DeDora et al. teach a method for preparing near-infrared fluorescent dye-loaded polymer microspheres, the method comprising: forming a complex of a near-infrared fluorescent dye and at least one selected from the group consisting of human serum albumin and cyclodextrin; and loading the complex into polymer microspheres.
Please see the discussion and citations within instant claim 1 for the relevant rejection text. Furthermore, Hwang et al. disclose preparing near-infrared fluorescent dye-loaded polymer microspheres (see page 1056, RESULTS Synthesis and Characterization of PLGA Nanoparticles; within Hwang et al.).
Regarding instant claim 13, Hwang et al. and DeDora et al. teach wherein the complex is loaded into the polymer microspheres using a water-in-oil-in-water (W1/O/W2) emulsion.
Hwang et al. disclose preparing near-infrared fluorescent dye-loaded polymer microspheres using a water-in-oil-in-water (W1/O/W2) emulsion (see page 1056, RESULTS Synthesis and Characterization of PLGA Nanoparticles; within Hwang et al.).
Combination of Hwang et al., DeDora et al., and Shults et al.
Regarding instant claim 14, Hwang et al., DeDora et al., and Shults et al. teach wherein the loading comprises mixing the near-infrared fluorescent dye with a hydrogel polymer.
Shults et al. disclose the use of a hydrogel polymer (see column 32, lines 44-50 within Shults et al.). Thus, a skilled artisan (POSITA) would use the hydrogel polymer of Shults et al. with the disclosure of Hwang et al. under routine experimental conditions.
Combination of Hwang et al., DeDora et al., and Ingber et al.
Regarding instant claim 15, Hwang et al., DeDora et al., and Ingber et al. teach a composition for marking lesions, comprising the near-infrared fluorescent dye-loaded polymer microspheres of instant claim 1.
Ingber et al. disclose a method of imaging lesions (see paragraph [00256] sections 52, 108, and 139 within Ingber et al.). Therefore, by imaging the lesions can be marked by medical personnel. Thus, a skilled artisan (POSITA) would use the lesion marking/imaging procedure of Ingber et al. with the disclosure of Hwang et al. under routine experimental conditions. Furthermore, Hwang et al. supports the marking/labelling of lesions (see instant claim 1).
Combination of Hwang et al. and DeDora et al.
Regarding instant claims 17 and 19, Hwang et al. and DeDora et al. teach wherein the composition is injectable through a syringe.
Hwang et al. disclose wherein the composition is injectable through a syringe (see page 1055, Animal Experiments and Islet Transplantation; within Hwang et al.).
Combination of Hwang et al., DeDora et al., and Magin et al.
Regarding instant claim 18, Hwang et al., DeDora et al., Magin et al. teach wherein the composition is in the form of a solid pellet.
Magin et al. disclose suitable compositions and dosage forms include, for example, dispersions, suspensions, solutions, syrups, granules, beads, powders, pellets,…(see page 43, lines 16-17 within Magin et al.). [By definition a pellet is in a solid form.] Therefore, a skilled artisan (POSITA) would use the solid pellet form of Magin et al. with the disclosure of Hwang et al. under routine experimental conditions.
Analogous Art
The Hwang et al., DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. references are directed to the same field of endeavor as the instant claims, that is, a near-infrared fluorescent dye-loaded polymer microsphere, as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the PLGA nanoparticles containing iron oxide and indocyanine green disclosed by Hwang et al., using the teachings of DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. in order to arrive at the subject matter of the instant claims.
The Hwang et al., DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. references all have considerable overlap in the polymeric microsphere or dye arts. In this instance, Hwang et al. supplies the template for the near-infrared fluorescent dye-loaded polymer microspheres, DeDora et al. supplies the complex of a near-infrared fluorophore (ICG) and a cyclodextrin that increases the fluorescence stability of the fluorophore, Ito et al. supplies the use of the surfactant, PVA, while Ingber et al., Magin et al., and Shults et al. supplies support for claim specific parameters within the polymeric microsphere and dye arts. All references are directed to either polymeric microspheres or dyes. These citations therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the six references when seeking to develop a near-infrared fluorescent dye-loaded polymer microsphere.
Given these teachings, a POSITA would have been motivated to combine the near-infrared fluorescent dye-loaded polymer microspheres as disclosed by Hwang et al., the complex of a near-infrared fluorophore (ICG) and a cyclodextrin that increases the fluorescence stability of the fluorophore disclosed by DeDora et al., the use of the surfactant, PVA, disclosed by Ito et al., and the claim specific parameters within the polymeric microsphere and dye arts disclosed by Ingber et al., Magin et al., and Shults et al.
The modification constitutes a simple substitution of one known element for another to obtain a predictable result [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar composition in the same way [MPEP §2143(I)(C)].
The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR].
The combination of the PLGA nanoparticles containing iron oxide and indocyanine green taught by Hwang et al. along with the use of the necessary claim limitations taught by DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
Furthermore, the additional claim limitations taught by DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. would have been viewed by a POSITA as routine design optimizations or known modifications for near-infrared fluorescent dye-loaded polymer microspheres. The motivation to combine the six references would be to create a near-infrared fluorescent dye-loaded polymer microspheres capable of marking lesions. Implementing these features in Hwang et al.’s PLGA nanoparticles containing iron oxide and indocyanine green would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Hwang et al., DeDora et al., Ito et al., Ingber et al., Magin et al., and Shults et al. provides all the elements of the claimed invention. The resulting near-infrared fluorescent dye-loaded polymer microspheres, constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Conclusion
No claims are allowed.
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