# US 10,441,768 B2 · Bioactive components conjugated to substrates of microneedle arrays > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,768 B2 - Document ID: US10441768B2 - Status: Granted - Kind: B2 - Application number: 15/074,917 - Filed: 2016-03-18 - Published: 2016-09-22 - Granted: 2019-10-15 - Earliest claimed: 2015-03-18 - Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education - Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education - Inventors: Louis D. Falo, Jr.; Geza Erdos - Web page: https://patentgrep.com/patent/US10441768B2 ## CPC - A61M 37/0015: {by using microneedles} - B29C 39/025: {for making multilayered articles} - B29C 39/123: {Making multilayered articles} - B29C 41/22: Making multilayered or multicoloured articles - B29C 41/34: Component parts, details or accessories; Auxiliary operations - A61M 2037/0023: {Drug applicators using microneedles} - A61M 2037/0046: {Solid microneedles} - A61M 2037/0053: {Methods for producing microneedles} - A61M 2037/0061: {Methods for using microneedles} - A61M 2202/0007: introduced into the body - A61M 2202/0057: retained by adsorption - B29K 2001/08: {Cellulose derivatives} - B29K 2995/006: Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible - B29L 2031/753: {Medical equipment; Accessories therefor (bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008)} - B29L 2031/7544: {Injection needles, syringes} - B29L 2031/756: {Microarticles, nanoarticles} - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS - B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES ## Abstract Microneedle arrays and methods of forming the same can include one or more bioactive components bonded to a biocompatible material such that the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material. ## Claims ### Claim 1 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and one or more bioactive components conjugated to the biocompatible material, wherein the one or more bioactive components are cleavable in vivo by an enzyme to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material. ### Claim 2 (depends on 1) The microneedle array of claim 1, wherein the biocompatible material is carboxymethylcellulose. ### Claim 3 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond. ### Claim 4 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both. ### Claim 5 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive components comprise Doxorubicin. ### Claim 6 (depends on 5) The microneedle array of claim 5, wherein the amount of Doxorubicin ranges from about 1 to 1000 μg for chemotherapy. ### Claim 7 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion. ### Claim 8 (depends on 7) The microneedle array of claim 7, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material. ### Claim 9 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material. ### Claim 10 (depends on 9) The microneedle array of claim 9, wherein the at least two different bioactive components are selected from the group consisting of a chemotherapeutic agent, an adjuvant, and a chemo attractant for a cancer chemo immunotherapy application. ### Claim 11 (depends on 9) The microneedle array of claim 9, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application. ### Claim 12 (depends on 1) The microneedle array of claim 1, wherein the one or more bioactive component comprises at least one viral vector. ### Claim 13 (depends on 12) The microneedle array of claim 12, wherein the at least one viral vector comprises an adenovector. ### Claim 14 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and a first bioactive component conjugated to the biocompatible material, the bioactive component being Doxorubicin, wherein the first bioactive component is cleavable in vivo by an enzyme to release the first bioactive component from the biocompatible material, or the first bioactive component retains function when conjugated to the biocompatible material. ### Claim 15 (depends on 14) The microneedle array of claim 14, wherein the biocompatible material is carboxymethylcellulose. ### Claim 16 (depends on 14) The microneedle array of claim 14, wherein the first bioactive component is bonded to the biocompatible material by a disulfide bond. ### Claim 17 (depends on 14) The microneedle array of claim 14, wherein the first bioactive components is cleavable in vivo in response to pH, temperature, or both. ### Claim 18 (depends on 14) The microneedle array of claim 14, wherein the amount of Doxorubicin ranges from about 1 to 1000 μg for chemotherapy. ### Claim 19 (depends on 14) The microneedle array of claim 14, further comprising a second bioactive component. ### Claim 20 (depends on 19) The microneedle array of claim 19, wherein the second bioactive component is selected from the group consisting of Poly-IC or Poly-ICLC. ### Claim 21 (depends on 19) The microneedle array of claim 19, wherein the second bioactive component is also conjugated to the biocompatible material. ### Claim 22 (depends on 19) The microneedle array of claim 19, wherein the second bioactive component is mixed into the biocompatible material. ### Claim 23 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and one or more bioactive components conjugated to the biocompatible material, wherein the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material, and wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme. ### Claim 24 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive components are covalently bonded to the biocompatible material. ### Claim 25 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond. ### Claim 26 (depends on 23) The microneedle array of claim 23, wherein the biocompatible material is carboxymethylcellulose. ### Claim 27 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive components comprise Doxorubicin. ### Claim 28 (depends on 27) The microneedle array of claim 27, wherein the amount of Doxorubicin ranges from about 1 to 1000 μg for chemotherapy. ### Claim 29 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion. ### Claim 30 (depends on 29) The microneedle array of claim 29, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material. ### Claim 31 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material. ### Claim 32 (depends on 31) The microneedle array of claim 31, wherein the at least two different bioactive components are selected from the group consisting of a chemotherapeutic agent, an adjuvant, and a chemo attractant for a cancer chemo immunotherapy application. ### Claim 33 (depends on 31) The microneedle array of claim 31, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application. ### Claim 34 (depends on 23) The microneedle array of claim 23, wherein the one or more bioactive component comprises at least one viral vector. ### Claim 35 (depends on 34) The microneedle array of claim 34, wherein the at least one viral vector comprises an adenovector. ### Claim 36 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and one or more bioactive components conjugated to the biocompatible material, wherein the one or more bioactive components are cleavable in vivo by an enzyme to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material, and wherein the one or more bioactive component comprises at least one viral vector wherein the bioactive component is bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme. ### Claim 37 (depends on 36) The microneedle array of claim 36, wherein the one or more bioactive components are covalently bonded to the biocompatible material. ### Claim 38 (depends on 36) The microneedle array of claim 36, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond. ### Claim 39 (depends on 36) The microneedle array of claim 36, wherein the biocompatible material is carboxymethylcellulose. ### Claim 40 (depends on 36) The microneedle array of claim 36, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both. ### Claim 41 (depends on 36) The microneedle array of claim 36, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion. ### Claim 42 (depends on 41) The microneedle array of claim 41, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material. ### Claim 43 (depends on 36) The microneedle array of claim 36, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material. ### Claim 44 (depends on 43) The microneedle array of claim 43, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application. ### Claim 45 (depends on 36) The microneedle array of claim 36, wherein the at least one viral vector comprises an adenovector. ### Claim 46 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and one or more bioactive components conjugated to the biocompatible material, wherein the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material, and wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application. ### Claim 47 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components are covalently bonded to the biocompatible material. ### Claim 48 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond. ### Claim 49 (depends on 46) The microneedle array of claim 46, wherein the biocompatible material is carboxymethylcellulose. ### Claim 50 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components are cleavable in vivo by an enzyme. ### Claim 51 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both. ### Claim 52 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components further comprise Doxorubicin. ### Claim 53 (depends on 52) The microneedle array of claim 52, wherein the amount of Doxorubicin ranges from about 1 to 1000 μg for chemotherapy. ### Claim 54 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion. ### Claim 55 (depends on 54) The microneedle array of claim 54, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material. ### Claim 56 (depends on 46) The microneedle array of claim 46, wherein the one or more bioactive component further comprises at least one viral vector. ### Claim 57 (depends on 56) The microneedle array of claim 56, wherein the at least one viral vector comprises an adenovector. ### Claim 58 A dissolvable microneedle array for transdermal insertion into a patient comprising: a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and a first bioactive component conjugated to the biocompatible material, the bioactive component being Doxorubicin, wherein the first bioactive component is cleavable in vivo to release the first bioactive component from the biocompatible material, or the first bioactive component retains function when conjugated to the biocompatible material, and wherein the second bioactive component is mixed into the biocompatible material wherein the bioactive components are bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme. ### Claim 59 (depends on 58) The microneedle array of claim 58, wherein the first bioactive component is covalently bonded to the biocompatible material. ### Claim 60 (depends on 58) The microneedle array of claim 58, wherein the first bioactive component is bonded to the biocompatible material by a disulfide bond. ### Claim 61 (depends on 58) The microneedle array of claim 58, wherein the biocompatible material is carboxymethylcellulose. ### Claim 62 (depends on 58) The microneedle array of claim 58, wherein the first bioactive components is cleavable in vivo in response to pH, temperature, or both. ### Claim 63 (depends on 58) The microneedle array of claim 58, wherein the amount of Doxorubicin ranges from about 1 to 1000 μg for chemotherapy. ### Claim 64 (depends on 58) The microneedle array of claim 58, wherein the second bioactive component is selected from the group consisting of Poly-IC or Poly-ICLC.