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 .
The response dated 3/30/2026 is acknowledged. Claims 14-15 and 19-22 are elected. Claims 1-9 are cancelled. Claims 10-13 and 16-18 are withdrawn. Claims 14-15 and 19-22 are considered on the merits below.
Response to Amendment
Applicant's amendments, filed 3/30/2026, with respect to the previous 112b rejections have been fully satisfied and withdrawn.
In response to the applicant's amendments, the grounds of rejection for claims 14-15 and 19-22 are new compared to the previous action, however rely on some of the same prior art.
Claim Objections
Claim 14 is objected to because of the following informalities:
The strike-through of the deleted complex is not easily perceived. Double brackets may be used (e.g., [[4]]) (MPEP 714). As an alternative to using double brackets, the applicant can cancel the claim and present the correct version as a new claim (e.g. claim 23).
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 14-15 and 19-22 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.
Regarding claim 14, the claim is drawn to a complex, however also includes method limitations for determining the purity of a component of the complex. This renders the claim indefinite because it is unclear if these are require or if the compounds listed in the evaluation are part of the complex or if they are solely a piece of the evaluation process. For examination purposes the examiner interprets that the compounds listed are solely a piece of the evaluation process. Thus the complex of Formula (I) only needs to be capable of being evaluated under these method conditions (i.e. a reacting the complex with nitrogen-containing nucleophile in the presence of a protonic acid in a polar solvent and then passing the complex through an HPLC).
If the applicant indents to indicate that the at least 95% bound-drug purity gives formula structural distinction from a complex without 95% bound-drug purity, then this needs to be more clearly indicated. This could potentially be achieve by a limitation similar to claim 19, which provides an amount of bound drug within the structure, or a negative claim (if supported in the specification) regarding the amount of other bound compounds not present.
Dependent claims follow the same reasoning.
Claim Rejections - 35 USC § 102
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 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) 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Říhová et al. (Journal of Drug Targeting, 2011; 19(10): 890–899).
Regarding claim 14, Říhová describes a complex of Formula (I):
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wherein A is a hydrogen atom or (R)-tetrahydro-2H-pyran-2-yl; b, c, d, and e each independently are a positive integer; and the bond indicated by a wavy line represents that the complex has either E or Z configuration, or a pharmaceutically acceptable salt thereof (figure 1 A is H, b is 5, and c, d, and e are integers),
wherein a drug contained in the complex of Formula (I) or the pharmaceutically acceptable salt thereof has a purity of not less than 95.0% as evaluated by reacting the complex of Formula (I) or the pharmaceutically acceptable salt thereof with at least one nitrogen-containing nucleophile selected from the group consisting of hydroxylamine, O-alkylhydroxylamine, and carboxylic acid hydrazide in the presence of a protonic acid in a polar solvent; and evaluating the purity of the reaction mixture obtained by the reaction step, by high- performance liquid chromatography (Examiner’s note: See 112b rejection above, the prior art only needs to be capable of satisfying these conditions. Říhová: Figure 1 shows 100% purity of complex of the drug contained in Formula (I)).
Claim(s) 14 and 19-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Etrych et al. ( J. Appl. Polym. Sci., 109: 3050-3061, 2008).
Regarding claim 14, Etrych describes a complex of Formula (I):
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wherein A is a hydrogen atom or (R)-tetrahydro-2H-pyran-2-yl; b, c, d, and e each independently are a positive integer; and the bond indicated by a wavy line represents that the complex has either E or Z configuration, or a pharmaceutically acceptable salt thereof (scheme 1 “polymer conjugates” A is H, b is 5, and c, d, and e are integers),
wherein a drug contained in the complex of Formula (I) or the pharmaceutically acceptable salt thereof has a purity of not less than 95.0% as evaluated by reacting the complex of Formula (I) or the pharmaceutically acceptable salt thereof with at least one nitrogen-containing nucleophile selected from the group consisting of hydroxylamine, O-alkylhydroxylamine, and carboxylic acid hydrazide in the presence of a protonic acid in a polar solvent; and evaluating the purity of the reaction mixture obtained by the reaction step, by high- performance liquid chromatography (Examiner’s note: See 112b rejection above, the prior art only needs to be capable of satisfying these conditions. Etrych: scheme 1 shows 100% purity of complex of the drug contained in Formula (I)).
Regarding claim 19, Etrych describes the complex or the pharmaceutically acceptable salt thereof according to claim 14, wherein the amount of the carried bound drug is 4 to 20 wt% (Etrych: page 3058 “The hydrophobic character of DOX bound to the conjugates becomes significant after drug loading exceeds 13 wt %.”).
Regarding claim 20, Etrych describes the complex or the pharmaceutically acceptable salt thereof according to claim 14, wherein the polar solvent is an alcoholic solvent; the nitrogen-containing nucleophile is at least one selected from the group consisting of hydroxylamine and carboxylic acid hydrazide; and the protonic acid is a carboxylic acid (Examiner’s note: See 112b rejection above, the prior art only needs to be capable of satisfying these conditions.).
Regarding claim 21, Etrych describes the complex or the pharmaceutically acceptable salt thereof according to claim 14, wherein the polar solvent is methanol; the nitrogen-containing nucleophile is at least one selected from the group consisting of hydroxylamine, acetohydrazide, propanohydrazide, butyrohydrazide, and 3- methylbutanohydrazide; and the protonic acid is acetic acid (Examiner’s note: See 112b rejection above, the prior art only needs to be capable of satisfying these conditions.).
Regarding claim 22, Etrych describes the complex or the pharmaceutically acceptable salt thereof according to of claim 14, wherein in the General Formula (I), b is an integer of 1 to 10; c is an integer of 30 to 500; d is an integer of 1 to 50; and e is an integer of 1 to 50 (Etrych: scheme 1 b is 5, and pages 3052-3053 “Statistical copolymers of HPMA with Ma-ah-NHNH2 or Ma-GFLG-NHNH2 (polymers 2–6, Table I, Scheme 1) containing free hydrazide groups were prepared by radical copolymerization in methanol (AIBN, 0.6–1.0 wt %; monomer concentration 18 wt %; molar ratio HPMA: Ma-ah-NHNH2/Ma-GFLGNHNH2 93 : 7 or 88 : 12; 608C; 17 h). Example of polymerization: HPMA (2.0 g, 14 mmol), Ma-ah- NHNH2 (227 mg, 1.06 mmol), and AIBN (96 mg, 0.58 mmol) was dissolved in methanol (12.7 mL).” these synthetic ratios correspond to the ranges required by the claim for c, d, and e.).
Allowable Subject Matter
Claim 15 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
References Říhová et al. (Journal of Drug Targeting, 2011; 19(10): 890–899) and Etrych et al. ( J. Appl. Polym. Sci., 109: 3050-3061, 2008) describe most of the limitations of claim 5, however fail to teach or suggest “A is (R)-tetrahydro-2H-pyran-2-yl”.
None of the prior art discovered describes all the limitations alone or in combination, thus the prior art fails to teach or suggest all the limitations of claims 15.
Response to Arguments
Applicant's arguments filed 3/30/2026 have been fully considered but they are not persuasive.
The Examiner appreciates the detailed description of the goal of the claims. However, most of what is indicated does not appear in the claim language.
Additionally, the applicant argues that Etrych teaches away from 95% purity required by the claim.
In response to the applicants argument that Etrych teaches away from 95% purity required by the claim , “the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” (MPEP 2145). In this case, as illustrated in Etrych, scheme 1 shows 100% purity of complex of the drug contained in Formula (I) of the claim.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY R BERKELEY whose telephone number is (571)272-9831. The examiner can normally be reached M-Th 9-6.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
/EMILY R. BERKELEY/
Examiner
Art Unit 1796
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