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 .
DETAILED ACTION
No preliminary amendment was submitted. The claims filed on 07/02/2024 are acknowledged. Claims 1-20 are pending in the instant application and are examined on the merits herein.
Priority
This application claims benefit to provisional application 63/525,233 filed on 07/06/2023.
Information Disclosure Statement
The information disclosure statements (IDS) dated 10/15/2024 and 11/04/2024 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
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 1-4, 6 and 10 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024).
Auzely-Velty is drawn to hydrogels made of glycosaminoglycans such as hyaluronic acid, having reversible linkages using boroxole derivatives. The glycosaminoglycans are crosslinked via an alkoxyboronate ester anion formed between a backbone diol function of a first glycosaminoglycan and a boronate hemiester grafted to a second glycosaminoglycan (abstract). Auzely-Velty exemplifies a hyaluronic acid covalently linked via an amide bond to a boronated moiety (page 36).
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Accordingly, the claims are anticipated by the art.
Claims 1 and 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zelenetskii et al. (Polymers, published 02/13/2018, PTO-892).
Zelenetskii is drawn to the study of polycomplexes of hyaluronic acid and borates in a solid state and solution and the application in boron neutron capture therapy (BNCT) (title). Zelentskii teaches that in order to provide biocompatibility to boron compounds for BNCT, it is necessary to create a system of covalently-bonded elements in one complex molecule. Zelentskii disclosed a synthesis of complex boron and high-Z element compounds for in-sample dosimetry, tumor localization and boron dose evaluation (page 2)
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Accordingly, the claims are anticipated by the art.
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.
Claims 1 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024) and Kim et al. (Journal of Pharmaceutical Investigation, published 03/19/2022, IDS dated 11/04/2024).
Claim 1 is rejected as discussed above.
The teachings of Auzely-Velty are discussed above.
Auzely-Velty does not teach wherein the hydrogel is ionically crosslinked by multivalent cations.
Kim is drawn to the study of modulating hyaluronic acid-based hydrogels for controlled drug delivery (title). Kim teaches that multivalent cations have been used to harden hyaluronic acid-based hydrogels and that the crosslinking degree has an impact on the mechanical properties of the hydrogel, such as the contact angle, viscosity, storage and loss modulus. These results imply that ionic crosslinking of hydrogels can be tuned by varying the metal ion concentration (page 404).
It would have been prima facie obvious to combine the teachings of Auzely-Velty and Kim before the effective filing date of the claimed invention by modifying the hyaluronic acid hydrogel taught by Auzely-Velty by crosslinking the hydrogel with a multivalent cation as taught by Kim to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the hydrogel taught by Auzely-Velty by adding in a multivalent cation to ionically crosslink the hyaluronic acid because Kim teaches that multivalent cations may be used to tune the mechanical properties of the hydrogel. One of ordinary skill in the art would have a reasonable expectation of success because Kim teaches that multivalent cations have been used to harden hyaluronic acid-based hydrogels and can be used to tune the mechanical properties of the hydrogel.
Claims 1, 12-14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024).
Claim 1 is rejected as discussed above.
The teachings of Auzely-Velty are discussed above.
Auzely-Velty further teaches that the hydrogel is easy to inject as the reversible bonds break when pushed through the syringe, and then quickly reform inside the body (page 4).
Auzely-Velty does not exemplify a kit comprising the hydrogel and a syringe.
Although Auzely-Velty is silent on a kit, it would have been prima facie obvious to one of ordinary skill in the art to prepare a kit based on the prior art because the grouping together of various objects or compositions directed to a common purpose (i.e. forming a kit) when all the individual objects or compositions are prima facie obvious over the prior art does not make the kit patentable. The idea of preparing a kit based on a prima facie obvious composition flows logically from the perspective of providing organization, convenience and quality control.
Claims 1, 5, 9, 12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Magda et al. (Polymer Degradation and Stability, published 11/12/2013, PTO-892) and Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024).
Magda is drawn to the study of boronic acid-containing smart hydrogels (title). Magda teaches that hydrogels could be used with minor modification to deliver boron to tumors during boron neutron capture therapy (BNCT) (abstract). Magda teaches that currently, low molecular weight pharmaceuticals such as boronophenylalanine (BPA) or
sodium borocaptate (BSH) are used to deliver 10B nuclei to the site of a tumor. However, as the concentration of 10B nuclei that can be delivered by BSH to tumor cells is limited to about 100 ppm, there is interest in increasing BNCT therapeutic effectiveness by using high molecular weight delivery agents that contain multiple boron atoms such as polymers, dendrimers, or micelles (page 219). The instant specification lists sodium borocaptate as a thiol-substituted dodecarborate compound (instant specification page 7).
Magda does not teach that the hydrogel comprises hyaluronic acid. Magda does not teach a kit comprising a reservoir and a boronated hydrogel.
The teachings of Auzely-Velty are discussed above.
Auzely-Velty further teaches that hyaluronic acid is one of the most widely used biocompatible polymers for medical use. Hyaluronic acid is present with identical chemical structure except for its molecular mass in most living organisms, it gives a minimum of foreign body reactions and allows for advanced medical uses (page 2).
It would have been prima facie obvious to combine the teachings of Magda and Auzely-Velty before the effective filing date of the claimed invention by substituting the polymer in the hydrogel taught by Magda to be hyaluronic acid as taught by Auzely-Velty to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the polymer taught by Magda with hyaluronic acid as taught by Auzely-Velty because Magda teaches that hydrogels may be modified with BSH to increase BNCT therapeutic effectiveness and Auzely-Velty teaches that hyaluronic acid is one of the most widely used biocompatible polymers for medical use. One of ordinary skill in the art would have a reasonable expectation of success because Magda teaches that hydrogels may be modified with BSH to increase BNCT therapeutic effectiveness and Auzely-Velty teaches that hyaluronic acid is one of the most widely used biocompatible polymers for medical use.
It would have been prima facie obvious to combine the teachings of Magda and Auzely-Velty before the effective filing date of the claimed invention by preparing a kit based on the prior art because the grouping together of various objects or compositions directed to a common purpose (i.e. forming a kit) when all the individual objects or compositions are prima facie obvious over the prior art does not make the kit patentable. The idea of preparing a kit based on a prima facie obvious composition flows logically from the perspective of providing organization, convenience and quality control.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Magda et al. (Polymer Degradation and Stability, published 11/12/2013, PTO-892) and Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024) as applied to claim 1 above, and further in view of Campkin et al. (Molecules, published 05/26/2022, PTO-892).
Claim 1 is rejected as discussed above.
The combined teachings of Magda and Auzely-Velty is discussed above.
The combined teachings of Magda and Auzely-Velty do not teach that the boronated moieties comprise residues of aminoalkyl dioxaborolane compounds or minoalkyl phenyl dioxaborolane compounds.
Campkin is drawn to tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesized via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT) (abstract). Campkin teaches that the introduction of boron atoms to drug molecules provides access to potential BNCT agents (page 2). Campkin uses a compound that meets the limitation of both aminoalkyl dioxaborolane compounds and aminoalkyl phenyl dioxaborolane and conjugates the compound to a thalidomide analogue utilizing the ester bond for the synthesis (Scheme 1, page 3)
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Campkin reaction scheme (scheme 1, page 3).
It would have been prima facie obvious to combine the combined teachings of Magda and Auzely-Velty with the teachings of Campkin before the effective filing date of the claimed invention by substituting the BSH moiety on the hyaluronic acid hydrogel taught by the combined teachings of Magda and Auzely-Velty with the aminoalkyl phenyl dioxaborolane compound taught by Campkin to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the BSH moiety with the aminoalkyl phenyl dioxaborolane compound because both moieties are taught for the same purpose of boron neutron capture therapy. One of ordinary skill in the art would have a reasonable expectation of success because both the BSH moiety and the aminoalkyl phenyl dioxaborolane compound are taught for the same purpose of boron neutron capture therapy.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Auzely-Velty et al. (WO 2018/024795 A1, published 02/08/2018, IDS dated 10/15/2024) as applied to claim 12 above, and further in view of Kim et al. (Journal of Pharmaceutical Investigation, published 03/19/2022, IDS dated 11/04/2024).
Claim 12 is rejected as discussed above.
The teachings of Auzely-Velty are discussed above.
Auzely-Velty does not teach wherein the hydrogel is ionically crosslinked by multivalent cations.
The teachings of Kim are discussed above.
It would have been prima facie obvious to combine the teachings of Auzely-Velty and Kim before the effective filing date of the claimed invention by modifying the hyaluronic acid hydrogel taught by Auzely-Velty by crosslinking the hydrogel with a multivalent cation as taught by Kim to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the hydrogel taught by Auzely-Velty by adding in a multivalent cation to ionically crosslink the hyaluronic acid because Kim teaches that multivalent cations may be used to tune the mechanical properties of the hydrogel. One of ordinary skill in the art would have a reasonable expectation of success because Kim teaches that multivalent cations have been used to harden hyaluronic acid-based hydrogels and can be used to tune the mechanical properties of the hydrogel.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zelenetskii et al. (Polymers, published 02/13/2018, PTO-892) and Barth et al. (Clinical Cancer Research, published 06/01/2005, PTO-892).
The teachings of Zelenetskii are discussed above.
Zelentskii does not teach administering the hydrogel by injection to a patient or specifically treating surface cancer.
Barth is drawn to the study of boron neutron capture therapy of cancer (title). Barth teaches that BNCT has been used to treat cutaneous melanomas which would meet the limitation of a surface cancer (page 3996). BNCT may be used to Barth teaches that boronated compounds may be directly injected into a subject. Delivery of boron agents to brain tumors is dependent on (a) the plasma concentration profile of the drug, which depends on the amount and route of administration; (b) the ability of the agent to traverse the BBB; (c) blood flow within the tumor; and (d) the lipophilicity of the drug. Enhancing the delivery of BPA and BSH can have a dramatic effect on both increasing tumor boron uptake and the efficacy of BNCT (page 3992).
It would have been prima facie obvious to combine the teachings of Zelentskii and Barth before the effective filing date of the claimed invention by applying the hyaluronic acid-borate complex that may be used in BCNT to treat tumors as taught by Zelentskii to a subject with cutaneous melanomas as taught by Barth to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the hyaluronic acid-borate complex for BCNT as taught by Zelentskii to a subject with cutaneous melanoma because Zelentskii teaches that the hyaluronic acid-borate complex may be used for BCNT treatment of tumors and Barth teaches that boron compounds may be injected into a subject for BCNT treatment of cutaneous melanoma. One of ordinary skill in the art would have a reasonable expectation of success because Zelentskii teaches that the hyaluronic acid-borate complex would increase bioavailability and Barth teaches that boron compounds may be injected into a subject for BCNT treatment of cutaneous melanoma.
Conclusion
No claims allowed.
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/S.L.S./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner,
Art Unit 1693
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