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 .
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.
Claim Status
Applicant’s amendment of 10/22/2025 is acknowledged. Claim 1 is amended. Claims 1-15 are currently pending.
Election/Restrictions
An election of invention/species was required in the instant application as detailed in the Office action dated 05/27/2025. The election is maintained and claims 10-15 remain withdrawn. Accordingly, claims 1-9 are examined on the merits herein.
The Examiner notes that the species election was extended to include non-elected small molecules comprising at least one amine group taught by Mou et al. (Poly. Adv. Technol., vol. 23, p. 748-755; published: 04/28/2011), and subsequently the art was applied in the instant Office action to expedite prosecution.
Priority
The instant application is a 371 of PCT/EP2021/052304 filed on 02/01/2021 and claims foreign priority to EP20154946.6 filed on 01/31/2020 as reflected in the filing receipt dated on 07/14/2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/22/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objections and Rejections
Applicant’s amendment to independent claim 1 and argument regarding the term “hyperbranched”, which was found to be persuasive, have overcome/rendered moot the previous 112(b) rejections. Thus, the rejections are hereby withdrawn.
Applicant's amendment has prompted the new grounds of rejection presented herein under 112(a) and 112(b).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
New Matter Rejection
Claims 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The limitation “wherein the small molecule is an organic compound having a molecular weight of less than 1 kDa” has been added to independent claim 1 in the amendment filed on 10/22/2025. However, the instant disclosure does not provide support for the entirety of the range “less than 1 kDa”. In particular, the instant specification and claims as originally filed do not disclose molecular weights of less than 100 Da, and only provides support for small molecules having a molecular weight within the range of 100 Da to 1000 Da (Instant Specification, page 1, lines 22-23). As a result, claim 1 represents new matter.
Claims 2-9 are rejected by virtue of their dependency on claim 1, as they do not resolve the written description deficiency.
If Applicant believes this rejection is in error, Applicant must disclose where in the specification support for the entire scope of the amendment(s) and/or new claims can be found.
Claim Rejections - 35 USC § 112(b)
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 1-9 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 recites the limitation “wherein the small molecule is an organic compound having a molecular weight of less than 1 kDa”. The lower limit broadly encompasses any molecular weight less than 1 kDa, including 0 kDa, which would correspond to the absence of a small molecule. It is unclear how a small molecule could be required and also meet the limitation wherein its molecular weight can be 0 kDa. Thus, without a defined lower limit to the recited range, the claim is indefinite. For the purposes of compact prosecution, the Examiner is interpreting the claim to mean that the small molecule has a molecular weight within the range of 100 Da to 1000 Da (same as 1 kDa), as supported by Applicant’s instant disclosure (Instant Specification, page 1, lines 22-23).
Claims 2-9 are rejected by virtue of their dependency on claim 1, as they fail to resolve the ambiguity in question.
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, 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, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Mou et al. (Poly. Adv. Technol., vol. 23, p. 748-755; published: 04/28/2011; PTO-892 of 08/01/2025) in view of Ferraro et al. (Biomacromolecules, vol. 19, p. 4524-4533; published: 11/09/2018; IDS of 08/29/2022).
Mou discloses the use of poly(ɛ-caprolactone)-b-hyperbranched polyglycidol core-shell micelles to encapsulate and enhance the solubility of hydrophobic drugs, such as the anticancer drug paclitaxel, in water (Page 748, Abstract and Page 755, Conclusion). Paclitaxel is a small molecule comprising an aliphatic amine, which reads on the small molecule recited in instant claims 1 and 3. The paclitaxel-encapsulated micelles were prepared by dissolving paclitaxel and copolymer in acetone and then adding the solution dropwise into water (Page 749, Hydrophobic drug loading), which reads on the limitation wherein no bond is formed between the hyperbranched polyester polyol derivative and the small molecule as recited in instant claim 8 and the aqueous solvent recited in instant claim 9.
However, Mou does not expressly teach that the poly(ɛ-caprolactone)-b-hyperbranched polyglycidol is sulfated as required by instant claim 1.
Ferraro teaches that sulfation of hyperbranched polyglycerols containing oligocaprolactone chains (hPG-co-PCLS) results in the construction of core-shell systems that are able to undergo acidic or enzymatic cleavage, allowing for improved biodegradability and cell compatibility compared to unsulfated analogs (Page 4525, R. Col.). Specifically, glycidol and ε-caprolactone are copolymerized at 50 °C in a 4:1 molar ratio and in the presence of Sn(oct)2 catalyst, followed by sulfation of the unsulfated precursor through reaction with sulfur trioxide pyridine complex (Page 4526, General Procedure for the Synthesis of Sulfated hPG-co-PCLS). The resulting sulfated copolymer is well tolerated by different cell lines and is a promising candidate for a therapeutic application in inflammation (Pages 4531-4532, Conclusion).
Regarding instant claim 1, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the micelle solution of Mou by substituting the poly(ɛ-caprolactone)-b-hyperbranched polyglycidol copolymer with the sulfated hPG-co-PCLS copolymer of Ferraro according to known methods to yield the predictable result of a drug-loaded core-shell micelle comprising a sulfated hyperbranched polyester polyol derivative and a small molecule comprising at least one amine group. One of ordinary skill in the art would have been motivated to use a sulfated hyperbranched glycidol/ε-caprolactone copolymer because the reference teaches that it results in improved biodegradability and cell compatibility compared to unsulfated analogs and also allows the additional advantage of being able to undergo acidic or enzymatic cleavage, which reduces accumulation of the micelles organs (Ferraro, Page 4525, L. Col.). One of ordinary skill in the art would have a reasonable expectation of success because both Mou and Ferraro teach the use of core-shell hyperbranched glycidol/ε-caprolactone micelles in biomedical applications (Ferraro, Page 4525, L. Col.).
The Examiner notes that instant claim 1 is a product-by-process claim. The patentability of a product-by-process claim is based on the product itself and does not depend on its method of production. Note: MPEP 2113(I). Because the composition taught by the combination of Mou and Ferraro is structurally the same as the instantly claimed product, it meets the claim.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Mou et al. (Poly. Adv. Technol., vol. 23, p. 748-755; published: 04/28/2011; PTO-892 of 08/01/2025) in view of Ferraro et al. (Biomacromolecules, vol. 19, p. 4524-4533; published: 11/09/2018; IDS of 08/29/2022), as applied to claims 1, 3, 8, and 9 above, and further in view of Scrivano et al. (Drug Deliv., vol. 24(1), p. 482-490; published: 02/09/2017; PTO-892 of 08/01/2025).
The combination of Mou and Ferraro teach the composition of instant claims 1, 3, 8, and 9 as discussed in detail above and further incorporated herein.
However, the combination of Mou and Ferraro do not expressly teach that the small molecule component of the composition comprises a non-aromatic cyclic amine as recited in instant claim 2, has a pKa value of more than 5 as recited in instant claim 4, is a heterocyclic tumor signal transduction inhibitor comprising at least one cyclic amine as recited in instant claim 5, or is chosen from the group recited in instant claims 6 or 7. Further, the combination of Mou and Ferraro does not expressly teach that the small molecule corresponds to Applicant’s elected species, sunitinib.
Scrivano teaches that sunitinib is a small molecular anticancer drug classified as a tyrosine kinase inhibitor, along with imatinib, gefitinib, erlotinib, afatinib, dasatinib, bosutinib, and ponatinib (Page 483, L. Col.). Sunitinib is classified as a class IV drug, which is characterized by low bioavailability due to low solubility and low permeability (Page 483, L. Col.). Scrivano further teaches that because sunitinib is poorly soluble in water and ethanol, its therapeutic effect may be limited in physiological aqueous media (Page 483, R. Col.). Sunitinib comprises a non-aromatic cyclic amine and an aliphatic amine and thus reads on the small molecule recited in instant claims 1-3 and 6-7, as well as Applicant’s elected species. It has a pKa of 11.4, as evidenced by Applicant’s instant specification (Page 8, Table 1), which lies within and thus renders obvious the range recited in instant claim 4. Scrivano teaches it is an anticancer tyrosine kinase inhibitor, and thus it reads on the heterocyclic tumor signal transduction inhibitor comprising at least one cyclic amine as recited in instant claim 5.
Regarding instant claims 1-9, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the micelle solution taught by the combination of Mou and Ferraro by substituting paclitaxel with another hydrophobic anticancer drug, sunitinib, as taught by Scrivano. One of ordinary skill in the art would have been motivated to use the core-shell micelle of Mou and Ferraro to encapsulate the sunitinib of Scrivano in order to enhance its solubility in a therapeutically-relevant physiological aqueous environment, thereby improving its therapeutic effect upon delivery, as taught by Scrivano. One of ordinary skill in the art would have a reasonable expectation of success because Mou teaches that core-shell micelles comprised of hyperbranched glycidol/ε-caprolactone copolymers are suitable for encapsulating and enhancing the solubility of hydrophobic drugs, including anticancer drugs.
Response to Arguments
Applicant’s arguments submitted on 10/22/2025 with respect to rejections under 35 U.S.C. 103 have been fully considered in so far as they apply to the new or modified rejections of the instant Office action, but were not found to be persuasive.
Applicant argues that the structure of the instantly claimed compound differs from the core-shell micelles of Mou, noting that the instant compound requires the caprolactone and glycerol residues to be randomly arranged rather than arranged as a block copolymer. Applicant further argues that due to these differences, Mou cannot be used as a starting point to arrive at the instant invention. This argument was not found to be persuasive in light of the prior art rejections of record, in which Ferraro provides reasonable motivation to modify Mou to arrive at a drug-loaded micelle with enhanced properties. In the rejections, the Examiner proposes that it is prima facie obvious to modify Mou by substituting the poly(ɛ-caprolactone)-b-hyperbranched polyglycidol copolymer with the sulfated hPG-co-PCLS copolymer of Ferraro in order to achieve improved biodegradability and cell compatibility compared to unsulfated analogs and the ability to undergo acidic or enzymatic cleavage, which reduces accumulation in organs. Contrary to Applicant’s argument, the combination of Mou and Ferraro results in a composition comprising a small molecule encapsulated in the hPG-co-PCLS copolymer of Ferraro, which Applicant admits is “essentially the same hyperbranched polyester polyol derivativ[e] as the present patent application” (Page 8 of Applicant’s Remarks filed 10/22/2025). Moreover, Ferraro teaches the exact same method steps as instantly recited in the product-by-process claims (cited above in the prior art rejections of record) and as such, the copolymer would necessarily have the same structure as the instantly claimed hyperbranched polyester polyol derivative, wherein the residues are randomly arranged.
Absent any objective evidence to the contrary, mixing paclitaxel—which has a molecular weight of approximately 854 Da (calculated by Examiner) and thus lies within the instantly claimed range—and copolymer in aqueous solution, as taught by Mou in view of Ferraro, would necessarily stabilize the small molecule through non-covalent interactions with the copolymer. This conclusion is further supported by Applicant’s instant specification, wherein a small molecule is encapsulated by the hyperbranched polyester polyol derivative by mixing the two materials in aqueous solution (Instant Specification, page 16). Therefore, the combination of Mou and Ferraro teaches all features of the instantly claimed composition.
Regarding Applicant’s argument that using Ferraro as a starting point would not guide a person skilled in the art towards the presently claimed invention, nor would a skilled person in the art consider modifying Ferraro with Mou: While the Examiner respectfully disagrees with Applicant’s position, this argument is moot in view of the prior art rejections of record, which use Mou as the primary teaching reference rather than Ferraro.
Applicant further argues that a combination of Ferraro and Scrivano would not guide a skilled artisan towards the presently claimed invention, given that the conjugates of Scrivano rely on a covalent bond between the protein sericin and the small molecule sunitinib. While the Examiner again notes that the rejections of record rely on Mou as the primary teaching reference rather than Ferraro, Applicant’s argument was still not found to be persuasive. The teachings of Scrivano, as discussed in detail above, identify limitations to therapeutic delivery of sunitinib, which like the paclitaxel of Mou is a hydrophobic and poorly soluble anti-cancer drug. While Scrivano utilizes a protein-drug conjugate to deliver the drug, the Examiner’s rejection proposes an alternative solution, whereby one hydrophobic and poorly soluble small molecule is substituted for another in order to enhance the solubility of sunitinib in a therapeutically-relevant physiological aqueous environment. The Examiner’s rejection does not rely on the covalent bond formed between sunitinib and the protein of Scrivano, and Applicant provides no objective evidence to support the assertion that “a skilled person in the art would – if at all – come to a compound in which sunitinib is covalently bound to a carrier molecule”. The combined teachings of Mou and Ferraro support a structure wherein the hydrophobic small molecule is, instead, encapsulated by copolymer through non-covalent interactions. Moreover, the Examiner notes that the instant limitation “wherein the small molecule is stabilized by the hyperbranched polyester polyol derivative due to non-covalent interactions” does not actually exclude additional stabilization by covalent interactions.
In view of the foregoing, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of objective evidence to the contrary. Therefore, the prior art rejections of record are maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SARAH CLINKSCALES WISTNER whose telephone number is (571)270-7715. The examiner can normally be reached Monday - Thursday 8:00 AM - 5:00 PM ET.
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/SARAH C WISTNER/ Examiner, Art Unit 1616
/MINA HAGHIGHATIAN/ Primary Examiner, Art Unit 1616