DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Status of the Claims
The response filed 12/01/2025 is acknowledged.
The claims filed 10/17/0223 are under consideration.
Claims 1-20 are pending.
Applicant’s election of Group I, claims 1-9 in the reply filed on 12/01/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 10-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/01/2025.
Claims 1-9 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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 3-8 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 pre-AIA the applicant regards as the invention.
Claim 3 includes the limitation methoxy polyethylene aldehyde (mPEG-CHO). It is not entirely clear what this means. mPEG suggests this is methoxy polyethylene glycol. However, the text only reads methoxy polyethylene aldehyde which suggests there is no glycol. Further, CHO may refer to cholesterol, i.e., methoxy polyethylene glycol conjugated to cholesterol (CHO), or the skilled artisan may understand “CHO” to an aldehyde functional group. In the latter case, the limitation appears to be a product by process limitation since the aldehyde will react, e.g., with the cholesterol hydroxyl group, depending on the presence or absence of other components in the carrier. The skilled artisan cannot reasonably determine the metes and bounds for which applicant is claiming protection.
Dependent claims do not clarify this issue.
The molar ratio of claim 5 cannot be searched because it is not clear what mPEG-CHO means. This may, for example, be a product by process limitation which includes the ratios of the reactants rather than the final product. That is, if the methoxy polyethylene aldehyde reacts with the cholesterol during preparation, it is not clear what the cholesterol-mPEG ratio of the carrier would be relative to the DOTAP and unmodified cholesterol in the carrier. Alternatively, the mPEG-CHO ratio value may refer to the ratio of mPEG modified cholesterol relative to the DOTAP and unmodified cholesterol.
The percent limitation of claim 6 cannot be considered for similar reasons because it is not clear what mPEG-CHO means.
Clarification is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Fernandes, US 20200163899.
Fernandes teaches a composition comprising Prussian blue nanoparticles in the form of nanocubes (Fernandes, e.g., 0005, Abstract, claims, e.g., claim 1, Fig. 9 and 0229). Fernandes teaches the Prussian blue nanocubes formulated by encapsulating in a liposome (Fernandes, e.g., 0041, 0088, 0172, 0249, and claim 15, and claim 70, and claim 93).
Encapsulation in a liposome means the Prussian blue nanocubes are coated with the lipid components of the liposome. See Fernandes, e.g., Fig. 8.
Since the composition comprises Prussian blue, it is suitable for promoting Fenton reactions in the same way as claimed.
Fernandes anticipates the subject matter of instant claims 1-2.
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 of this title, 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.
Claims 1-2 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Fernandes, US 20200163899 in view of Guo, US 20150246137.
The teachings of Fernandes enumerated above are reiterated here. Fernandes teaches compositions comprising Prussian blue nanocubes present in an amount effective for photothermal treatment but does not expressly teach an amount ranging from 1-10 wt%.
However, Guo teaches liposomes may contain at least about 10 wt% of the liposome as bioactive compound (Guo, e.g., claim 1). Amounts ranging from 1.38 wt% to 47.1wt% are found in Guo, e.g., 0066, table 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious before the effective filing date of the presently claimed invention to modify carrier compositions comprising Prussian blue nanocubes encapsulated in liposomes by optimizing the amount of active Prussian blue nanocubes using known guidance found in Guo with a reasonable expectation of success. The claimed range is within and overlapping with the amount of active known to be effectively loaded in liposomes as taught by Guo. The skilled artisan would have had a reasonable expectation of success because Guo teaches amounts of active agent encapsulation amounts for liposomes and Fernandes teaches encapsulating the Prussian blue nanocubes in liposomes.
Accordingly, the subject matter of claims 1-2 and 9 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Fernandes, US 20200163899 in view of Guo, US 20150246137 and Zhao, Journal of Pharmaceutical Sciences, 2007.
For this rejection mPEG-CHO is interpreted to refer to mPEG modified cholesterol.
Fernandes teaches carrier compositions comprising Prussian blue nanocube active agent encapsulated in a liposome to protect the Prussian blue nanocubes when administered (Fernandes, e.g., 0041), e.g., the liposome contains lipid components (Fernandes, e.g., see claim 17, particle coated with various lipid components).
Fernandes does not expressly teach the lipid component includes a combination of DOTAP, mPEG-CHO, and cholesterol.
However, Guo teaches liposomes comprising a cationic lipid, a PEG-modified lipid, and cholesterol. Guo teaches DOTAP allows the cargo to be internalized by tumor cells more effectively and pegylation can help the nanoparticles improve drug pharmacokinetics and improve bioavailability (Guo, e.g., 0070). Guo teaches lipid combinations including cholesterol and DOTAP (Guo, e.g., 0097). Guo teaches liposomes comprising lipid combinations including DOTAP, cholesterol, and a pegylated lipid, e.g., DSPE-PEG (Guo, e.g., 0138, and scheme 1 and 0148 and 0316 and example 1, e.g., 0320 and example 6, e.g., 0367-398, and example 27). Methoxy polyethylene glycol is found in Guo, e.g., 0316, with reference to DSPE-PEG2000.
Guo does not expressly teach mPEG-cholesterol. However, Zhao teaches liposomes modified with mPEG-cholesterol was a known technique effective as a bi-layer anchor to inhibit aggregation of liposomes and increase in vivo circulation of the cholesterol anchored liposomes (Zhao, e.g., Abstract and pp. 2432-2433). Zhao suggests mPEG-cholesterol was an art recognized equivalent for DSPE-PEG employed by Gao and offers advantages over DSPE, e.g., reduced protein binding, and is more chemically stable than DSPE (Zhao, e.g., Abstract and pp. 2432-2433).
It would have been obvious before the effective filing date of the presently claimed invention to modify liposome encapsulated Prussian blue nanocube formulations suggested by Fernandes using improved liposome formulation techniques known from Gao and Zhao to improve the formulations in the same way with a reasonable expectation of success. The skilled artisan would have been motivated to employ DOTAP, cholesterol, and a methoxy pegylated lipid for improved internalization by tumor cells and improved pharmacokinetics suggested by Gao. The skilled artisan would have been motivated to modify methoxy PEG DSPE containing formulations exemplified in Gao with methoxy PEG cholesterol for improved stability and reduced plasma protein binding as reported in Zhao. Zhao provides an express suggestion to substitute methoxy PEG cholesterol for methoxy PEG DSPE to obtain improved formulation stability and reduced plasma protein binding. The skilled artisan would have had a reasonable expectation of success because each document teaches liposomal formulations.
Applicable to claims 5 and 7: Guo teaches cationic lipids, e.g., DOTAP, present in an amount ranging from about 20-80%, e.g., 20-60% (Guo, e.g., 0096). Guo teaches DOTAP and cholesterol present in a 1:1 ratio (Guo, e.g., 0097). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Applicable to claims 5 and 8: Guo teaches neutral lipids, e.g., cholesterol, present in an amount ranging from about 40-80% (Guo, e.g., 0096). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Applicable to claims 5 and 6: Guo teaches pegylated lipids present in an amount ranging from about 5-20% (Guo, e.g., 0127). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Accordingly, the subject matter of claims 1-9 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim(s) 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-9 of US 12502353 in view of Fernandes, US 20200163899 in view of Guo, US 20150246137 and Zhao, Journal of Pharmaceutical Sciences, 2007.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The reference claims teach a composition comprising a nanocube of Prussian blue encapsulated by a liposome.
The reference claims anticipate the subject matter of claims 1-2.
The reference claims do not expressly teach the lipid composition of claims 3-8. However, the lipid composition of claims 3-8 is suggested by the combined teachings of Fernandes, Guo and Zhao as enumerated above.
It would have been obvious before the effective filing date of the presently claimed invention to modify a composition comprising liposome encapsulated Prussian blue nanocubes of the reference claims using techniques for improving liposomes and therapeutic methods thereof known from the combined teachings of Fernandes, Guo, and Zhao with a reasonable expectation of success. The skilled artisan would have been motivated to employ DOTAP, cholesterol, and a methoxy pegylated lipid for improved internalization by tumor cells and improved pharmacokinetics suggested by Gao. The skilled artisan would have been motivated to modify methoxy PEG DSPE containing formulations exemplified in Gao with methoxy PEG cholesterol for improved stability and reduced plasma protein binding as reported in Zhao. Zhao provides an express suggestion to substitute methoxy PEG cholesterol for methoxy PEG DSPE to obtain improved formulation stability and reduced plasma protein binding. The skilled artisan would have had a reasonable expectation of success because each document teaches liposomal formulations.
Applicable to claims 5 and 7: Guo teaches cationic lipids, e.g., DOTAP, present in an amount ranging from about 20-80%, e.g., 20-60% (Guo, e.g., 0096). Guo teaches DOTAP and cholesterol present in a 1:1 ratio (Guo, e.g., 0097). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Applicable to claims 5 and 8: Guo teaches neutral lipids, e.g., cholesterol, present in an amount ranging from about 40-80% (Guo, e.g., 0096). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Applicable to claims 5 and 6: Guo teaches pegylated lipids present in an amount ranging from about 5-20% (Guo, e.g., 0127). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Accordingly, the subject matter of claims 1-9 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615