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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15, in the reply filed on 7/22/2026 is acknowledged. Claims 1-21 are pending, of which claims 16-21 are withdrawn from consideration at this time as being directed to a non-elected invention. Claims 1-15 encompass the elected invention and are examined herein on the merits for patentability.
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 1-8 and 10-15 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. The claims are directed to a system for delivery of a drug in vivo … comprising a solvent system of dimethyl sulfoxide (DMSO) or its analogs for carrying the drug, etc. The claims are unclear with regard to what is encompassed by an “analog” of DMSO. For example, claim 9 states that the analog is selected from the group consisting of acetone, acetonitrile, methanol, ethanol, 1-propanol and 2-propanol. It is noted that the recited analog solvents have very little structural commonality with DMSO. It is considered that the identity of any other analog other than those listed in claim 9 is unclear, because it is not demarcated in what way a solvent is structurally and/or functionally related to DMSO in order to encompass an analog of DMSO. As such, the metes and bounds of the claims are not clearly set forth and the scope of the invention cannot be distinctly ascertained.
Claims 2 and 5 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 2 recites a macromolecular drug selected from a group including a DNA, RNA, or peptide. See MPEP 2173.05. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sznitowska et al. (WO 02/36582).
Snitzowska discloses stable pharmaceutical form of the anti-cancer drug containing paclitaxel of the Fig. 1, according to the invention, is characterised in that it is a stable form of the active substance of a large surface, amorphous, possibly with some fine-crystalline additive. According to the invention, the method for production of the stable pharmaceutical form of the anticancer drug consists in dissolution of crystalline paclitaxel in a neutral organic solvent selected from the group comprising acetonitrile, dioxane, ethanol, or a mixture of those solvents, with possible addition of water, providing that the control of individual solvents in the mixture is in the range of 5 % to 95 %, while the content of water is in the range of 0 to 60 % (abstract and claim 1).
In Example IV, 30 ml of ethanol were added to 40 ml of 1,4-dioxane. 1500 mg of paclitaxel were dissolved in that solvent. 30 ml of water were added. The resulting solution was sterilised in aseptic conditions by filtering through a 0.2 μm teflon filter. Then the solution was filled at the doses of 2 ml into 20-rnl sterile glass vials. The vials were provided with sterile rubber stoppers for freeze- drying.
It is noted that acetonitrile and ethanol are defined as DMSO analogs in instant claim 9. With regard to the limitation drawn to a “system for delivery of a drug in vivo wherein the extent of the delivery of the drug is monitorable and/or controllable by using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI)” and wherein the solvent system is “for carrying the drug, detecting the delivery and/or biodistribution the drug, and/or interaction of the drug compartmentalized in vivo by way of directly imaging the solvent system by the CEST MRI due to the inherent contrast of the solvent system,” it is noted that the intended use of the composition does not distinguish over the structural features of the solvent system.
With regard to claim 7 directed to CEST effects, it is noted that the functional recitation does not distinguish over Snitzowska. “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure or composition as that which is claimed, the properties applicant discloses and/or claims are necessarily present. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The “discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Power Co. v. Ireco Inc., 51 USPQ 2d 1943, 1947 (Fed. Cir. 1999). Therefore, merely claiming a new use, new function, or new property, which is inherently present in the prior art does not make the claim patentable. See In re Best, 195 USPQ 430, 433 (CCPA 1977), and MPEP § 2112.
With regard to claim 5, in Example 4, 1500 mg paclitaxel is provided = 1.76 mmol (based on 853.01 g/mol molecular weight) in 30 + 40 + 30 mL = 100 mL of solvent, which corresponds to a concentration of 17.6 mM of the drug.
Claim(s) 1-3, 5, 7, 14 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (Nanotechnology, 2019, 30 425102).
Xu discloses multifunctional nanomedicines featuring high drug loading capacity, controllable drug release and real-time self-monitoring are attracting increasing attention due to their potential to improve cancer therapeutic efficacy. Herein, a new kind of Fe3O4@C-based nanoparticles modified with isoreticular metal organic frameworks (IRMOF-3), folic acid (FA) and detachable polyethylene glycol (PEG) under tumor microenvironment was developed. The core-shell structured Fe3O4@C was synthesized via the one-pot solvothermal reaction and the IRMOF-3 layers were coated on the outer shell of Fe3O4@C through layer-by-layer coating method. The FA and PEG were conjugated on the surface of nanoparticles by reacting with the amine groups provided by IRMOF-3. The as-synthesized nanoparticles showed stable photothermal effect, superparamagnetic properties and blue fluorescence characteristic under 360 nm irradiation. The in vitro experiments showed that the drug loaded nanoparticles exhibit pH-dependent drug release property, and PEGylation was proved effective in suppressing burst drug release (only 8.0% of drugs were released within 95 h). The confocal laser scanning microscopy study revealed that the as-synthesized nanoparticles could serve as a cell imaging agent and the cell internalization can be significantly enhanced after FA modified. The IRMOF-3 modified nanoparticles showed negligible cytotoxicity and the drug loaded nanoparticles showed pH/photothermal-stimuli enhanced cytotoxicity in vitro. It is believed that the present smart drug delivery platforms will hold great potential in imaging guided drug delivery and cancer therapy.
In Section 2.7, synthesis of Fe3O4@C@MMOF-FA is taught. In a typical process, 10 mg of FA was dissolved in 10 ml mixed solvent (5ml DMSO and 5ml water), to which 40mg of EDC and 40mg of NHS were added. The final solution was kept at 25 °C for 24 h in the dark. 10mg of Fe3O4@C@MMOF nanoparticles were dispersed in 5 ml of DMSO and added to the above solution, then the reaction was continued for 24 h in dark. After the reaction was completed, the unreacted FA was washed away in DMSO solvent.
In Section 2.7, modification of Fe3O4@C@MMOF with mPEG-CHO is taught. In a typical process, 8 mg Fe3O4@C@MMOF was added into 6ml DMSO and sonicated to disperse. Then, 0.074g mPEG CHO was dissolved in 5ml DMSO and added into the above solution. This mixed solution was then heated to 40 °C and held for 6h. Then, the solution was dialyzed with a dialysis membrane (MWCO 3500Da) against aqueous Na2HPO4 solution (pH 8–8.5) for 24 h.
With regard to the limitation drawn to a “system for delivery of a drug in vivo wherein the extent of the delivery of the drug is monitorable and/or controllable by using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI)” and wherein the solvent system is “for carrying the drug, detecting the delivery and/or biodistribution the drug, and/or interaction of the drug compartmentalized in vivo by way of directly imaging the solvent system by the CEST MRI due to the inherent contrast of the solvent system,” it is noted that the intended use of the composition does not distinguish over the structural features of the solvent system.
With regard to claim 7 directed to CEST effects, it is noted that the functional recitation does not distinguish over Snitzowska. “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure or composition as that which is claimed, the properties applicant discloses and/or claims are necessarily present. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The “discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Power Co. v. Ireco Inc., 51 USPQ 2d 1943, 1947 (Fed. Cir. 1999). Therefore, merely claiming a new use, new function, or new property, which is inherently present in the prior art does not make the claim patentable. See In re Best, 195 USPQ 430, 433 (CCPA 1977), and MPEP § 2112.
With regard to claim 5, 10 mg/ 10 mL FA is provided. Based on the molecular weight of FA as 441.4 g/mol, the provided amount of drug corresponds to a concentration of 2.27 mM of the FA.
Claim(s) 1-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang et al. (Biomaterials, 2018, 166, 13-26).
Tang discloses the systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.
Gambogic acid, GA, a natural product extracted from the Garcinia hanburryi tree, has been demonstrated to exhibit potent anticancer activity against a wide range of cancers both in vitro and in vivo.
Table 2 shows a summary of the solvent effect on drug solubility, liposomal aggregation and drug loading. DSPC/Chol liposomes (55/45, mol%) with a loading gradient were used. Drug loading for 1 mg/mL of GA was performed at a D/L of 1/10, w/w) for 30 min at room temperature. The loading gradients for GA was 150 mM magnesium gluconate (page 17).
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Optimization of the liposomal formulation for enhanced therapy of cancer to demonstrate the utility of SALT. We first compared GA loading efficiency of the DSPC/Chol/DSPE-mPEG2K liposomes with different loading gradients, including magnesium gluconate, calcium formate, copper acetate (pH 5.2), and basified copper acetate (pH 9.5). As depicted in Fig. 1A, liposomes with all loading gradients achieved complete drug loading in the presence of 5 vol% DMSO at a drug-to-total lipid of 1/5 w/w (page 18).
In vitro drug retention analysis was performed with various liposomal GA formulations containing Did (page 15).
It is noted that acetonitrile and ethanol are defined as DMSO analogs in instant claim 9. With regard to the limitation drawn to a “system for delivery of a drug in vivo wherein the extent of the delivery of the drug is monitorable and/or controllable by using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI)” and wherein the solvent system is “for carrying the drug, detecting the delivery and/or biodistribution the drug, and/or interaction of the drug compartmentalized in vivo by way of directly imaging the solvent system by the CEST MRI due to the inherent contrast of the solvent system,” or “wherein the liposome is used as a probe” it is noted that the intended use of the composition does not distinguish over the structural features of the solvent system.
With regard to claim 7 directed to CEST effects, it is noted that the functional recitation does not distinguish over Snitzowska. “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure or composition as that which is claimed, the properties applicant discloses and/or claims are necessarily present. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The “discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Power Co. v. Ireco Inc., 51 USPQ 2d 1943, 1947 (Fed. Cir. 1999). Therefore, merely claiming a new use, new function, or new property, which is inherently present in the prior art does not make the claim patentable. See In re Best, 195 USPQ 430, 433 (CCPA 1977), and MPEP § 2112.
With regard to claim 5, 1 mg/mL GA is provided, based on the molecular weight at 628.7, corresponds to a concentration of 1.59 mM of the drug.
Conclusion
No claims are allowed at this time.
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/LHS/
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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