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 .
Claims 1-9 and 11-15 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I and the species: sulfate, a polycaprolactone, and a disulfide bridge in the reply filed on 09/12/2025 is acknowledged.
Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and claims 4 and 5 are withdrawn as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/12/2025.
Claims 1-3 and 6-9 are under current examination.
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 1-3 and 6-9 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 1, line 12 recites “the linker includes a hydrocarbon…”. This renders the claim indefinite because it is unclear whether the language following the word “includes” is a required limitation or merely providing examples of the types of linkers that can be embraced by the term “linker”.
Claim 3 is unclear because it does not identify the claim from which it depends. It is therefore, it is unclear what additional limitations are encompassed by this dependent claim. It is noted that claims must be given their broadest reasonable interpretation in light of the specification (See MPEP §2111) and therefore, for purposes of compact prosecution, the abovementioned claim is interpreted as dependent from claim 2 because claim 2 recites the term “redox-sensitive entity”, which is further limited in claim 3. Amendment to identify the claim from which claim 3 depends is required.
Claim 9 is indefinite because the claim could reasonably be interpreted to be internally contradictory. Specifically, the claim requires multiple amphiphilic copolymers of claim 1 but also requires “at least one”, which reads on a single copolymer. The claim is interpreted to claim more than one amphiphilic copolymer according to claim 1, wherein the copolymers are either identical to each other or differ chemically from one another while still falling within the scope of claim 1.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
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 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 1-3, 6, 7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (ACS Applied Materials & Interfaces, 8(41):27530-27538; publication date: 09/27/2016; cited in the IDS filed 07/31/2022) in view of Meng et al. (Nano Research 11(12):6177-6189; publication date: 2018).
The claims are examined in view of the following species elections:
(a) sulfate as the substitution on the polyglycerol backbone;
(b) a polycaprolactone as the hydrophobic block; and
(c) the linker is a hydrocarbon having at least six consecutive methylene residues and a disulfide bridge as the cleavable entity.
With regard to claim 1, Zhong discloses a micelle-forming dendritic sulfated polyglycerol conjugated by a disulfide-containing linker to polycaprolactone for drug delivery (dPGS-SS-PCL; abstract, title). Thus, Zhong discloses an amphiphilic copolymer comprising a first hydrophilic block that is a dendritic poly glycerol derivative having a polyglycerol backbone and carrying a plurality of sulfate residues substituting hydroxyl groups of the polyglycerol backbone (see schemes 1 and 2 where the sulfate groups are depicted), and a second hydrophobic block containing polycaprolactone. The micelles release drug under reducing conditions (abstract, page 27530, right col). With regard to the linker, Zhong discloses the following structure:
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This linker contains a cleavable entity, the disulfide group, as required by the instant claims; however, Zhong does not disclose a linker having a hydrocarbon having at least six consecutive methylene residues and that is devoid of the triazole-containing residue excluded by instant claim 1.
Meng, in the analogous art of polymer micelles for drug delivery disclose that drugs may be covalently linked to polymer by linkers such as 3,3’-dithiodipropionic acid (DDPA) or 4,4’-dithiodibutyric acid (DDBA; disulfide linkers respectively containing two propionic or two butyric acid moieties joined together by the disulfide bond; see scheme 2 for structure) and that the length of the linker influences efficiency of delivery with the longer chain providing more effective delivery (abstract). The DDPA or DDBA are linked to hydroxyl containing moieties on the drug and the polymer by reaction with the drug/polymer hydroxyl groups with carboxylic acid groups at either ends of the linkers (see scheme 2). Disassembly of the conjugate [and consequent drug release] occurs due to collapse of the disulfide bond in a reducing environment (abstract). One having ordinary skill in the art would have recognized DDPS or DDBS as redox-sensitive disulfide-containing linker suitable to join substances together via pendant hydroxyl groups.
It would have been prima facie obvious to replace the triazole-containing linker disclosed by Zhong with the linkers disclosed by Meng, which lack the triazole group because they were both known to serve the same purpose: linking compounds together such that they will degrade and release drug in a reducing environment, such as a cancer cell. The skilled artisan would have had reasonable expectation of success because Meng’s linkers can also be conjugated to molecules having pendant hydroxyl groups as do polyglycerol sulfate and polycaprolactone. With regard to the limitation of instant claim 1 requiring at least six consecutive methylene residues, the specific linkers disclosed by Meng contain fewer methylene groups than required by the claim. However, as explained in MPEP 2144.09(II): Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). Moreover, Meng indicates that length of the spacer can affect efficiency of drug delivery, providing one of ordinary skill a motivation to explore longer chain lengths in a micelle-forming polymer conjugate such as those rendered obvious by Zhong/Meng.
With regard to claims 2 and 3, the disulfide is a redox-sensitive entity.
With regard to claim 6, as noted above, increasing the number of methylene groups in the conjugate of Zhong/Meng would have been routine exploration/optimization for the artisan of ordinary skill, e.g. an individual with a Ph.D. in polymer synthesis/cancer research/pharmaceutical sciences.
With regard to claim 7, the PCL-SS had a molecular weight of 3.7 kd/mol (page 27531, left col). Using a molecular weight of g/mol for caprolactone, the hydrophobic block contained approximately 32 repeating caprolactone units. This falls within the scope required by the instant claims.
With regard to claim 9, as noted above, the amphiphilic copolymer forms micelles (title), which would contain a plurality of the amphiphilic copolymers.
Claims 1-3 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (ACS Applied Materials & Interfaces, 8(41):27530-27538; publication date: 09/27/2016; cited in the IDS filed 07/31/2022) in view of Licha et al. (US 2011/0065896; publication date: 03/17/2011).
The claims are examined in view of the following species elections:
(a) sulfate as the substitution on the polyglycerol backbone;
(b) a polycaprolactone as the hydrophobic block; and
(c) linker including a hydrocarbon having at least six consecutive methylene residues and a disulfide bridge as the cleavable entity.
With regard to claim 1, Zhong discloses a micelle forming dendritic sulfated polyglycerol conjugated by a disulfide-containing linker to polycaprolactone for drug delivery (dPGS-SS-PCL; abstract, title). Thus, Zhong discloses an amphiphilic copolymer comprising a first hydrophilic block that is a dendritic polyglycerol derivative having a polyglycerol backbone and carrying a plurality of sulfate residues substituting hydroxyl groups of the polyglycerol backbone (see schemes 1 and 2 where the sulfate groups are depicted), and a second hydrophobic block containing polycaprolactone. The micelles release drug under reducing conditions (abstract, page 27530, right col). With regard to the linker, Zhong discloses the following structure:
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This linker contains a cleavable entity, the disulfide group, as required by the instant claims; however, Zhong does not disclose a linker having a hydrocarbon having at least six consecutive methylene residues and that is devoid of the triazole-containing residue excluded by instant claim 1.
Licha, in the analogous art of polyether polyol dendron conjugates for drug delivery (abstract) discloses that molecules may be conjugated to each other by linker units having C1-12 aliphatic hydrocarbon chains wherein at least one of the carbon atoms is replaced by a group selected from -O-, -S-, and -C(O)NH- (0107). The linker may contain a disulfide (0122), which one having ordinary skill would have recognized as resulting from replacing two consecutive carbons with a -S-.
It would have been prima facie obvious to replace the triazole-containing linker disclosed by Zhong with the linkers disclosed by Licha, which lack the triazole group because they were both known to serve the same purpose, linking compounds together such that they will degrade and a disulfide containing linker can release drug in a reducing environment, such as a cancer cell.
With regard to claims 2 and 3, the disulfide is a redox-sensitive entity.
With regard to claim 6, as noted above, the number of carbons disclosed by Licha for their aliphatic hydrocarbon linker overlaps with the number required by the instant claims. See MPEP 2144.05.
With regard to claim 7, the PCL-SS had a molecular weight of 3.7 kd/mol (page 27531, left col). Using a molecular weight of g/mol for caprolactone, the hydrophobic block contained approximately 32 repeating caprolactone units. This falls within the scope required by the instant claims.
With regard to claim 8, the structure recited in the claim:
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falls within the scope of the genus of linkers disclosed by Licha, in that it is an aliphatic hydrocarbon having 6-20 consecutive methylene groups and substituted with -O-, -S-, and -C(O)NH-. There is overlap in the number of consecutive methylene groups permitted by the instant claims and the range disclosed by Licha for number of aliphatic carbons (see MPEP 2144.05).
With regard to claim 9,as noted above, the amphiphilic copolymer forms micelles (title), which would contain a plurality of the amphiphilic copolymers.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617