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 .
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.
Claims 1-4 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (Biomaterial Sci, Vol 8, 2019, pp1-12).
Wang discloses a method of delivering a therapeutic to a subject in need thereof (page 5, first paragraph, release kinetics of rapamycin from DBCO-hz-rapa conjugated alginate-N3 gels. to achieve sustained release of these free drugs over a long period; page 8, first paragraph, this approach potentially enables targeted delivery of immunosuppressive drugs to biomaterial depots at any time of interest, followed by sustained release of active drugs locally, which is anticipated to flexibly maintain immunosuppression after allotransplantation, i.e., a subject in need thereof), said method comprising: a) administering or implanting a functionalized hydrogel to the subject (page 7, third paragraph, balb/c mice were subcutaneously injected with alginate-N3), wherein said functionalized hydrogel comprises a hydrogel covalently attached directly or via a linker to an azide or alkyne group (abstract, hydrogel; page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N3 polymer chains via calcium ions), and b) administering a functionalized therapeutic and/or functionalized vesicle (optional) to the subject (page 7, third paragraph, balb/c mice were subcutaneously injected with alginate-N3 followed by i.v. injection of DBCO-hz-rapa, i.e., a functionalized therapeutic; page 5, first paragraph, rapamycin), wherein said functionalized therapeutic comprises a therapeutic covalently attached directly or via a linker to an azide or alkyne group (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer.. release kinetics of rapamycin from DBCO-hz-rapa conjugated alginate-N3 gels.. covalent conjugation to achieve sustained release of these free drugs over a long period; page 7, third paragraph, the enhanced capture of DBCO-hz-rapa by alginate-N gels via Click chemistry), wherein said functionalized vehicle comprises a vehicle covalently attached directly or via a linker to an azide or alkyne group (optional), and wherein said functionalized vehicle comprises and/or encapsulates a therapeutic (optional), wherein if said functionalized hydrogel comprises an azide (page 5, first paragraph, alginate-N3 gels), then said functionalized therapeutic and/or functionalized vesicle (optional) comprises an alkyne group (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer), and wherein if said functionalized hydrogel comprises an alkyne group, then said functionalized therapeutic and/or functionalized vesicle comprises an azide (optional).
Regarding Claim 2, Wang discloses the method of claim 1, the functionalized hydrogel coats and/or is contained within a scaffold (page 8, first paragraph, biomaterial depots, i.e., a scaffold, at any time of interest, followed by sustained release of active drugs locally, which is anticipated to flexibly maintain immunosuppression after allotransplantation. Alginate gels as evaluated in our platform are natural non-immunogenic polysaccharides, enable controlled local release of drugs, and are also refillable by binding fresh intravenously injected prodrugs. These gels, once implanted in tissues, do not require replacement every time the drug levels fall to sub-therapeutic thresholds, thus avoiding trauma and inflammation due to repeated gel injections).
Regarding Claim 3, Wang discloses the method of claim 12, wherein step b) comprises systemic administration (page 7, third paragraph, followed by i.v. injection of DBCO-hz-rapa).
Regarding Claim 4, Wang discloses the method of claim 1, wherein step b) comprises intravenous (page 7, third paragraph, followed by i.v. injection of DBCO-hz-rapa) and/or intraperitoneal administration.
Regarding Claim 5, it would have been obvious to perform the step repeatedly as needed for treatment.
Regarding Claim 11, Wang discloses the method of claim 1, wherein the functionalized hydrogel comprises alginate covalently attached to dibenzocyclooctyne (DBCO) via a linker (page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N polymer chains via calcium ions), wherein the functionalized therapeutic (page 7, third paragraph, DBCO-hz-rapa; page 5, first paragraph, rapamycin) is an antibiotic covalently attached directly or via a linker to an azide group (remains optional), and wherein the functionalized vesicle (remains optional) is a liposome covalently attached directly or via a linker to an azide group, and said liposome encapsulates an antibiotic (optional).
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 1-32 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Biomaterial Sci, Vol 8, 2019, pp1-12) in view of Ascendis (WO 2020/064844).
Regarding Claim 12, Wang discloses the method of claim 1, wherein the functionalized hydrogel comprises alginate covalently attached to an azide via a linker (page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N polymer chains via calcium ions), wherein the functionalized therapeutic is covalently attached directly or via a linker to dibenzocyclooctyne (DBCO) (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer. release kinetics of rapamycin from DBCO-hz-rapa conjugated alginate-N3 gels covalent conjugation to achieve sustained release of these free drugs over a long period; page 7, third paragraph, the enhanced capture of DBCO-hz-rapa by alginate-N gels via Click chemistry), and wherein the functionalized vesicle (remains optional) is a liposome covalently attached directly or via a linker to dibenzocyclooctyne (DBCO) (optional), and said liposome encapsulates an antibiotic (optional).
Wang fails to teach wherein the functionalized therapeutic is an antibiotic.
Ascendis in the field of pharmaceutical compositions (abstract) teaches wherein a functionalized therapeutic is an antibiotic (page 21, lines 30-34; page 22, lines 1-3, pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt for use in a method of preventing or treating an infection, wherein said conjugate is water-insoluble and comprises a polymeric moiety -Z to which a plurality of moieties -L2-XOD-L1-D are covalently conjugated each -D is independently an antibiotic moiety; each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated).
It would have been obvious to one of ordinary skill in the art at the time of the Invention to modify Wang to include wherein a functionalized therapeutic is an antibiotic as taught by Ascendis, for the benefit of providing functionalized hydrogel covalently linked to a functionalized therapeutic (Wang: abstract; page 5, first paragraph; page 7, third paragraph) comprising an antibiotic moiety modified covalently with a linker to provide composition to efficiently treat chronic infections (Ascendis: abstract; page 1, lines 31-33; page 21, lines 30-34; page 22, lines 1-3).
Regarding Claim 16, Wang discloses a method of treating a subject in need thereof (page 5, first paragraph, release kinetics of rapamycin, i.e., from DBCO-hz-rapa conjugated alginate-N3 gels. to achieve sustained release of these free drugs over a long period; page 8, first paragraph, this approach potentially enables targeted delivery of immunosuppressive drugs to biomaterial depots at any time of interest, followed by sustained release of active drugs locally, which is anticipated to flexibly maintain immunosuppression after allotransplantation, i.e., a subject in need thereof), said method comprising: a) administering or implanting a functionalized hydrogel to the subject (page 7, third paragraph, balb/c mice were subcutaneously injected with alginate-N3), wherein said functionalized hydrogel comprises a hydrogel covalently attached directly or via a linker to an azide or alkyne group (abstract, hydrogel; page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N3 polymer chains via calcium ions), and b) administering a functionalized therapeutic and/or functionalized vesicle (optional) to the subject (page 7, third paragraph, balb/c mice were subcutaneously injected with alginate-N3. followed by i.v. injection of DBCO-hz-rapa, i.e., a functionalized therapeutic; page 5, first paragraph, rapamycin), wherein said functionalized therapeutic comprises a therapeutic covalently attached directly or via a linker to an azide or alkyne group (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer release kinetics of rapamycin from DBCO-hz-rapa conjugated alginate-N3 gels. covalent conjugation to achieve sustained release of these free drugs over a long period; page 7, third paragraph, the enhanced capture of DBCO-hz-rapa by alginate-N gels via Click chemistry), wherein said functionalized vehicle comprises a vehicle covalently attached directly or via a linker to an azide or alkyne group (optional), wherein said functionalized vehicle comprises and/or encapsulates a therapeutic (optional), wherein if said functionalized hydrogel comprises an azide (page 5, first paragraph, alginate-N3 gels), then said functionalized therapeutic and/or functionalized vesicle comprises an alkyne group (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer), and wherein if said functionalized hydrogel comprises an alkyne group, then said functionalized therapeutic and/or functionalized vesicle comprises an azide (optional).
Wang fails to disclose treating, inhibiting, and/or preventing a microbial or bacterial infection, comprising wherein said therapeutic is an antimicrobial or antibiotic.
Ascendis in the field of pharmaceutical compositions to treat an infection (abstract; page 1, lines 3-5) teaches treating, inhibiting, and/or preventing a microbial or bacterial infection, comprising wherein said therapeutic is an antimicrobial or antibiotic (page 1, line 5, pharmaceutically acceptable salt for use in a method of preventing or treating an infection; page 4, lines 25-33, daptomycin an antimicrobial drug for the prevention or treatment of bacterial infections, which either kills or inhibits growth of bacteria).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Wang to include wherein a functionalized therapeutic is an antibiotic as taught by Ascendis, for the benefit of providing functionalized hydrogel covalently linked to a functionalized therapeutic (Wang: abstract; page 5, first paragraph; page 7, third paragraph) comprising an antibiotic moiety modified covalently with a linker to provide composition to efficiently treat chronic infections (Ascendis: abstract; page 1, lines 5, 31-33; page 4, lines 25-33; page 21, lines 30-34; page 22, lines 1-3).
Regarding Claim 17, modified Wang discloses the method of claim 16, wherein the functionalized hydrogel coats and/or is contained within a scaffold (page 8, first paragraph, biomaterial depots, i.e., a scaffold, at any time of interest, followed by sustained release of active drugs locally, which is anticipated to flexibly maintain immunosuppression after allotransplantation. Alginate gels as evaluated in our platform are natural non-immunogenic polysaccharides, enable controlled local release of drugs, and are also refillable by binding fresh intravenously injected prodrugs. These gels, once implanted in tissues, do not require replacement every time the drug levels fall to sub-therapeutic thresholds, thus avoiding trauma and inflammation due to repeated gel injections).
Regarding Claim 18, modified Wang discloses the method of claim 16, wherein step b) comprises systemic administration (page 7, third paragraph, followed by i.v. injection of DBCO-hz-rapa).
Regarding Claim 19, modified Wang discloses the method of claim 16, wherein step b) comprises intravenous (page 7, third paragraph, followed by i.v. injection of DBCO-hz-rapa) and/or intraperitoneal administration.
Regarding Claim 25, modified Wang discloses the method of claim 16, wherein the functionalized hydrogel comprises alginate covalently attached to dibenzocyclooclyne (DBCO) via a linker (page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N polymer chains vía calcium ions), wherein the functionalized therapeutic (page 7, third paragraph, DBCO-hz-rapa; page 5, first paragraph, rapamycin) is an antibiotic covalently attached directly or via a linker to an azide group (remains optional), and wherein the functionalized vesicle (remains optional) is a liposome covalently attached directly or via a linker to an azide group, and said liposome encapsulates an antibiotic (optional).
Regarding Claim 26, modified Wang discloses the method of claim 16, wherein the functionalized hydrogel comprises alginate covalently attached to an azide via a linker (page 5, first paragraph, alginate-N3 gels, formed by crosslinking of alginate-N polymer chains via calcium ions), wherein the functionalized therapeutic is covalently attached directly or via a linker to dibenzocyclooctyne (DBCO) (page 5, first paragraph, after developing Clickable, acid-labile DBCO-hz-rapa, DBCO-hz-tacro, and DBCO-MPA, and demonstrated their capability to covalently conjugate to alginate-N polymer.. release kinetics of rapamycin from DBCO-hz-rapa conjugated alginate-N3 gels. Covalent conjugation to achieve sustained release of these free drugs over a long period; page 7, third paragraph, the enhanced capture of DBCO-hz-rapa by alginate-N gels via Click chemistry), and wherein the functionalized vesicle (remains optional) is a liposome covalently attached directly or via a linker to dibenzocyclooctyne (DBCO) (optional), and said liposome encapsulates an antibiotic (optional).
Wang fails to disclose wherein the functionalized therapeutic is an antibiotic.
Ascendis in the field of pharmaceutical compositions (abstract) teaches wherein a functionalized therapeutic is an antibiotic (page 21, lines 30-34; page 22, lines 1-3, pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt for use in a method of preventing or treating an infection, wherein said conjugate is water-insoluble and comprises a polymeric moiety -Z to which a plurality of moieties -L2-XOD-L1-D are covalently conjugated. each -D is independently an antibiotic moiety; each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Wang to include wherein a functionalized therapeutic is an antibiotic as taught by Ascendis, for the benefit of providing functionalized hydrogel covalently linked to a functionalized therapeutic (Wang: abstract; page 5, first paragraph; page 7, third paragraph) comprising an antibiotic moiety modified covalently with a linker to provide composition to efficiently treat chronic infections (Ascendis: abstract; page 1, lines 31-33; page 21, lines 30-34; page 22, lines 1-3).
Regarding Claim 29, it would have been obvious to administer the composition to any part of the body, including a bone flap.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN J PACKARD whose telephone number is (571)270-3440. The examiner can normally be reached Mon 2-6pm and Tues-Fri (9am-6pm + mid-day flex).
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/BENJAMIN J PACKARD/ Primary Examiner, Art Unit 1612