Claims for Patent: 9,402,910

Summary for Patent: 9,402,910

Title:	Internally functionalized graphene substrates
Abstract:	The present invention is generally directed to internally functionalized graphene substrates, methods of making such substrates and methods of using such substrates. In one aspect, the present invention is a graphene substrate. The substrate comprises edge and non-edge regions. Organic or inorganic molecules are bound to the non-edge regions of the substrate, and the organic or inorganic molecules are present on the substrate edges at a population greater than about one molecule per 10,000 nm.sup.2.
Inventor(s):	McKinney; Jeffrey Alan (Lafayette, CA), Martinez; William Emerson (Berkeley, CA)
Assignee:	Nanotech Biomachines, Inc. (Berkeley, CA)
Application Number:	14/120,928
Patent Claims:	1. A graphene substrate, wherein the substrate comprises edge and non-edge regions, and wherein organic or inorganic molecules are bound to a nucleophilic moiety covalently linked to a carbon molecule in the non-edge regions of the substrate, and wherein the organic or inorganic molecules are present on the non-edge regions at a population greater than about one molecule per 30,000 nm.sup.2. 2. The graphene substrate according to claim 1, wherein organic molecules are present on the substrate, and wherein the organic molecules are selected from a group consisting of: antibodies; antibody fragments; aptamers; large molecule therapeutics; oligonucleotides; oligopeptides; oligosaccharides, proteins and small molecule therapeutics. 3. The graphene substrate according to claim 2, wherein the population is greater than about 1 molecule per 10,000 nm.sup.2. 4. The graphene substrate according to claim 3, wherein the organic molecules are selected from a group consisting of: antibodies; antibody fragments; proteins; and, aptamers. 5. The graphene substrate according to claim 3, wherein the organic molecules are selected from a group consisting of: large molecule therapeutics; oligonucleotides; oligopeptides; oligosaccharides and small molecule therapeutics. 6. The graphene substrate according to claim 4, wherein the population is greater than about 1 molecule per 3,000 nm.sup.2. 7. The graphene substrate according to claim 5, wherein the population is greater than about 1 molecule per 3,000 nm.sup.2. 8. The graphene substrate according to claim 6, wherein the organic molecules are proteins, and wherein the proteins are selected from a group consisting of: Insulin; Pramlintide; Growth hormone; Mecasermin; Factor VIII; Factor IX; Antithrombin III; Protein C; B-Gluco-cerebrosidase; Alglucosidase-.alpha.; Laronidase; Idursulphase; Galsulphase; Agalsidase-.beta.; A-1-Proteinase inhibitor; Lactase; Lipase; Amylase; Protease; Adenosine deaminase; Human albumin; Erythropoietin; Darbepoetin-.alpha.; Filgrastim; Sargramostim; Oprelvekin; Human follicle-stimulating hormone; Human chorionic gonadotropin; Lutropin-.alpha.; Type I .alpha.-interferon; Interferon-.alpha.2a; Interferon-.alpha.2b; Interferon-.alpha.n3; Interferon-.beta.1a; Interferon-.beta.1b; Interferon-.gamma.1b; Aldesleukin; Alteplase; Reteplase; Tenecteplase; Urokinase; Factor VIIa; Drotrecogin-.alpha.; Salmon calcitonin; Teriparatide; Exenatide; Octreotide; Dibotermin-.alpha.; Recombinant human bone morphogenic protein 7; Histrelin; Palifermin; Becaplermin; Trypsin; Nesiritide; Botulinum toxin type A; Botulinum toxin type B; Collagenase; Human deoxy-ribonuclease I; Hyaluronidase; Papain; L-Asparaginase; Rasburicase; Lepirudin; Bivalirudin; Streptokinase; Anistreplase; Bevacizumab; Cetuximab; Panitumumab; Alemtuzumab; Rituximab; Trastuzumab; Abtacept; Anakinra; Adalimumab; Etanercept; Infliximab; Alefacept; Efalizumab; Natalizumab; Eculizumab; Antithymocyte globulin; Basiliximab; Daclizumab; Muromonab-CD3; Omalizumab; Palivizumab; Enfuvirtide; Abciximab; Pegvisomant; Crotalidae polyvalent immune Fab; Digoxin immune serum Fab; Ranibizumab; Denileukin diftitox; Ibritumomab tiuxetan; Gemtuzumab ozogamicin; Tositumomab; DNA polymerase. 9. The graphene substrate according to claim 7, wherein the organic molecules are large molecule therapeutics, and wherein the large molecule therapeutics are selected from a group consisting of: 5-alpha-reductase inhibitors; 5-aminosalicylates; 5HT3 receptor antagonists; adamantane antivirals; adrenal cortical steroids; adrenal corticosteroid inhibitors; adrenergic bronchodilators; agents for hypertensive emergencies; agents for pulmonary hypertension; aldosterone receptor antagonists; alkylating agents; alpha-glucosidase inhibitors; amebicides; aminoglycosides; aminopenicillins; aminosalicylates; AMPA receptor antagonists; amylin analogs; analgesics; androgens and anabolic steroids; angiotensin converting enzyme inhibitors; angiotensin II inhibitors; anorexiants; antacids; anthelmintics; anti-angiogenic ophthalmic agents; anti-CTLA-4 monoclonal antibodies; anti-infectives; antiadrenergic agents, centrally acting; antiadrenergic agents, peripherally acting; antiandrogens; antianginal agents; antiarrhythmic agents; antiasthmatic combinations; antibiotics/antineoplastics; anticholinergic antiemetics; anticholinergic antiparkinson agents; anticholinergic bronchodilators; anticholinergic chronotropic agents; anticholinergics/antispasmodics; anticoagulants; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antidiuretic hormones; antiemetic/antivertigo agents; antifungals; antigonadotropic agents; antigout agents; antihistamines; antihyperlipidemic agents; antihyperuricemic agents; antimalarial agents; antimalarial combinations; antimalarial quinolines; antimetabolites; antimigraine agents; antineoplastic detoxifying agents; antineoplastic interferons; antineoplastics; antiparkinson agents; antiplatelet agents; antipseudomonal penicillins; antipsoriatics; antipsychotics; antirheumatics; antiseptic and germicides; antithyroid agents; antitoxins and antivenins; antituberculosis agents; antituberculosis combinations; antitussives; antiviral agents; antiviral interferons; anxiolytics, sedatives, and hypnotics; aromatase inhibitors; atypical antipsychotics; azole antifungals; bacterial vaccines; barbiturate anticonvulsants; barbiturates; BCR-ABL tyrosine kinase inhibitors; benzodiazepine anticonvulsants; benzodiazepines; beta-adrenergic blocking agents; beta-lactamase inhibitors; bile acid sequestrants; bisphosphonates; bone resorption inhibitors; bronchodilators; calcineurin inhibitors; calcitonin; calcium channel blocking agents; carbamate anticonvulsants; carbapenems; carbonic anhydrase inhibitor anticonvulsants; carbonic anhydrase inhibitors; cardiac stressing agents; cardioselective beta blockers; cardiovascular agents; catecholamines; CD20 monoclonal antibodies; CD30 monoclonal antibodies; CD33 monoclonal antibodies; CD52 monoclonal antibodies; central nervous system agents; cephalosporins; cerumenolytics; CFTR potentiators; chemokine receptor antagonist; chloride channel activators; cholesterol absorption inhibitors; cholinergic agonists; cholinergic muscle stimulants; cholinesterase inhibitors; CNS stimulants; coagulation modifiers; colony stimulating factors; contraceptives; corticotropin; coumarins and indandiones; cox-2 inhibitors; dibenzazepine anticonvulsants; digestive enzymes; dipeptidyl peptidase 4 inhibitors; diuretics; dopaminergic antiparkinsonism agents; echinocandins; EGFR inhibitors; estrogen receptor antagonists; estrogens; factor Xa inhibitors; fatty acid derivative anticonvulsants; fibric acid derivatives; first generation cephalosporins; fourth generation cephalosporins; gamma-aminobutyric acid analogs; gamma-aminobutyric acid reuptake inhibitors; gastrointestinal agents; genitourinary tract agents; GI stimulants; glucocorticoids; glucose elevating agents; glycopeptide antibiotics; glycoprotein platelet inhibitors; glycylcyclines; gonadotropin releasing hormones; gonadotropin-releasing hormone antagonists; gonadotropins; group I antiarrhythmics; group II antiarrhythmics; group III antiarrhythmics; group IV antiarrhythmics; group V antiarrhythmics; growth hormone receptor blockers; growth hormones; guanylate cyclase-C agonists; H. pylori eradication agents; H2 antagonists; hedgehog pathway inhibitorshematopoietic stem cell mobilizer; heparin antagonists; heparins; HER2 inhibitors; histone deacetylase inhibitors; hormones; hormones/antineoplastics; hydantoin anticonvulsants; hydrazide derivatives; immune globulins; immunologic agents; immunostimulants; immunosuppressive agents; incretin mimetics; inotropic agents; insulin; insulin-like growth factor; integrase strand transfer inhibitor; interferons; interleukin inhibitors; interleukins; ketolides; leprostatics; leukotriene modifiers; lincomycin derivatives; loop diuretics; lymphatic staining agents; lysosomal enzymes; macrolide derivatives; macrolides; mast cell stabilizers; meglitinides; metabolic agents; methylxanthines; mineralocorticoids; mitotic inhibitors; monoamine oxidase inhibitors; mTOR inhibitors; mucolytics; multikinase inhibitors; muscle relaxants; mydriatics; narcotic analgesics; natural penicillins; neuraminidase inhibitors; neuromuscular blocking agents; neuronal potassium channel openers; next generation cephalosporins; nicotinic acid derivatives; NNRTIs; non-cardioselective beta blockers; non-sulfonylureas; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors (NRTIs); oxazolidinedione anticonvulsants; parathyroid hormone and analogs; penicillinase resistant penicillins; penicillins; peripheral opioid receptor antagonists; peripheral vasodilators; peripherally acting antiobesity agents; phenothiazine antiemetics; phenothiazine antipsychotics; phenylpiperazine antidepressants; plasma expanders; platelet aggregation inhibitors; platelet-stimulating agents; polyenes; potassium-sparing diuretics; probiotics; progesterone receptor modulators; progestins; prolactin inhibitors; prostaglandin D2 antagonists; protease inhibitors; proteasome inhibitors; proton pump inhibitors; psoralens; psychotherapeutic agents; purine nucleosides; pyrrolidine anticonvulsants; quinolones; recombinant human erythropoietins; renin inhibitors; respiratory agents; rifamycin derivatives; salicylates; sclerosing agents; second generation cephalosporins; selective estrogen receptor modulators; selective immunosuppressants; selective phosphodiesterase-4 inhibitors; selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; serotoninergic neuroenteric modulators; sex hormone combinations; sex hormones; SGLT-2 inhibitors; skeletal muscle relaxants; smoking cessation agents; somatostatin and somatostatin analogs; statins; streptomyces derivatives; succinimide anticonvulsants; sulfonamides; sulfonylureas; synthetic ovulation stimulants; tetracyclic antidepressants; tetracyclines; therapeutic radiopharmaceuticals; therapeutic vaccines; thiazide diuretics; thiazolidinediones; thioxanthenes; third generation cephalosporins; thrombin inhibitors; thrombolytics; thyroid drugs; TNF alfa inhibitors; tocolytic agents; triazine anticonvulsants; tricyclic antidepressants; trifunctional monoclonal antibodies; urea anticonvulsants; urea cycle disorder agents; urinary anti-infectives; urinary antispasmodics; vasodilators; vasopressin antagonists; vasopressors; VEGF/VEGFR inhibitors; viral vaccines. 10. The graphene substrate according to claim 7, wherein the organic molecules are oligonucleotides, and wherein the oligonucleotides are selected from a group consisting of: N.sub.1N.sub.2N.sub.3N.sub.4N.sub.5N.sub.6N.sub.7N.sub.8N.sub.9N.sub.10N.- sub.11N.sub.12N.sub.13N.sub.14N.sub.15N.sub.16N.sub.17N.sub.18N.sub.19N.su- b.20 where N.sub.1 is A, T, C or G; N.sub.2 is A, T, C or G; N.sub.3 is A, T, C or G; N.sub.4 is A, T, C or G; N.sub.5 is A, T, C, G, or no base; N.sub.6 is A, T, C, G, or no base; N.sub.7 is A, T, C, G, or no base; N.sub.8 is A, T, C, G, or no base; N.sub.9 is A, T, C, G, or no base; N.sub.10 is A, T, C, G, or no base; N.sub.11 is A, T, C, G, or no base; N.sub.12 is A, T, C, G, or no base; N.sub.13 is A, T, C, G, or no base; N.sub.14 is A, T, C, G, or no base; N.sub.15 is A, T, C, G, or no base; N.sub.16 is A, T, C, G, or no base; N.sub.17 is A, T, C, G, or no base; N.sub.18 is A, T, C, G, or no base; N.sub.19 is A, T, C, G, or no base; N.sub.20 is A, T, C, G, or no base. 11. The graphene substrate according to claim 7, wherein the organic molecules are oligopeptides, and wherein the oligopeptides are selected from a group consisting of: P.sub.1P.sub.2P.sub.3P.sub.4P.sub.5P.sub.6P.sub.7P.sub.8P.sub.9P.sub.10P.- sub.11P.sub.12P.sub.13P.sub.14P.sub.15P.sub.16P.sub.17P.sub.18P.sub.19P.su- b.20P.sub.21P.sub.22P.sub.23P.sub.24P.sub.25 where P.sub.1 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S or T; P.sub.2 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S or T; P.sub.3 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S or T; P.sub.4 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S or T; P.sub.5 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S or T; P.sub.6 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.7 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.8 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.9 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.10 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.11 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.12 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.13 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.14 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.15 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.16 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.17 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.18 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.19 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.20 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.21 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.22 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.23 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.24 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid; P.sub.25 is G, P, A, V, L, I M, C, R, Y, W, H, K, R, Q, N, E, D, S, T or no amino acid. 12. The graphene substrate according to claim 7, wherein the organic molecules are oligosaccharides, and wherein the oligosaccharides are selected from a group consisting of: S.sub.1S.sub.2S.sub.3S.sub.4S.sub.5S.sub.6S.sub.7S.sub.8S.sub.9S.sub.10S.- sub.11S.sub.12S.sub.13S.sub.14S.sub.15S.sub.16S.sub.17S.sub.18S.sub.19S.su- b.20S.sub.21S.sub.22S.sub.23S.sub.24S.sub.25 where S.sub.1 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, or N-acetylneuraminide; S.sub.2 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, or N-acetylneuraminide; S.sub.3 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.4 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.5 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.6 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.7 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.8 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.9 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.10 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.11 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.12 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.13 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.14 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.15 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.16 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.17 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.18 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.19 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.20 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.21 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.22 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.23 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.24 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide; S.sub.25 is glucose, fructose, glucopyranose, ribitol, gluconic acid, glucosamine, N-acetylneuraminide or no monosaccharide. 13. The graphene substrate according to claim 7, wherein the organic molecules are small molecule therapeutics, and wherein the small molecule therapeutics are selected from a group consisting of: 5-alpha-reductase inhibitors; 5-aminosalicylates; 5HT3 receptor antagonists; adamantane antivirals; adrenal cortical steroids; adrenal corticosteroid inhibitors; adrenergic bronchodilators; agents for hypertensive emergencies; agents for pulmonary hypertension; aldosterone receptor antagonists; alkylating agents; alpha-glucosidase inhibitors; alternative medicines; amebicides; aminoglycosides; aminopenicillins; aminosalicylates; AMPA receptor antagonists; amylin analogs; analgesics; androgens and anabolic steroids; angiotensin converting enzyme inhibitors; angiotensin II inhibitors; anorexiants; antacids; anthelmintics; anti-angiogenic ophthalmic agents; anti-CTLA-4 monoclonal antibodies; anti-infectives; antiadrenergic agents, centrally acting; antiadrenergic agents, peripherally acting; antiandrogens; antianginal agents; antiarrhythmic agents; antiasthmatic combinations; antibiotics/antineoplastics; anticholinergic antiemetics; anticholinergic antiparkinson agents; anticholinergic bronchodilators; anticholinergic chronotropic agents; anticholinergics/antispasmodics; anticoagulants; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antidiuretic hormones; antiemetic/antivertigo agents; antifungals; antigonadotropic agents; antigout agents; antihistamines; antihyperlipidemic agents; antihyperuricemic agents; antimalarial agents; antimalarial combinations; antimalarial quinolines; antimetabolites; antimigraine agents; antineoplastic detoxifying agents; antineoplastic interferons; antineoplastics; antiparkinson agents; antiplatelet agents; antipseudomonal penicillins; antipsoriatics; antipsychotics; antirheumatics; antiseptic and germicides; antithyroid agents; antitoxins and antivenins; antituberculosis agents; antituberculosis combinations; antitussives; antiviral agents; antiviral interferons; anxiolytics, sedatives, and hypnotics; aromatase inhibitors; atypical antipsychotics; azole antifungals; bacterial vaccines; barbiturate anticonvulsants; barbiturates; BCR-ABL tyrosine kinase inhibitors; benzodiazepine anticonvulsants; benzodiazepines; beta-adrenergic blocking agents; beta-lactamase inhibitors; bile acid sequestrants; bisphosphonates; bone resorption inhibitors; bronchodilators; calcineurin inhibitors; calcitonin; calcium channel blocking agents; carbamate anticonvulsants; carbapenems; carbonic anhydrase inhibitor anticonvulsants; carbonic anhydrase inhibitors; cardiac stressing agents; cardioselective beta blockers; cardiovascular agents; catecholamines; CD20 monoclonal antibodies; CD30 monoclonal antibodies; CD33 monoclonal antibodies; CD52 monoclonal antibodies; central nervous system agents; cephalosporins; cerumenolytics; CFTR potentiators; chemokine receptor antagonist; chloride channel activators; cholesterol absorption inhibitors; cholinergic agonists; cholinergic muscle stimulants; cholinesterase inhibitors; CNS stimulants; coagulation modifiers; colony stimulating factors; contraceptives; corticotropin; coumarins and indandiones; cox-2 inhibitors; dibenzazepine anticonvulsants; digestive enzymes; dipeptidyl peptidase 4 inhibitors; diuretics; dopaminergic antiparkinsonism agents; echinocandins; EGFR inhibitors; estrogen receptor antagonists; estrogens; factor Xa inhibitors; fatty acid derivative anticonvulsants; fibric acid derivatives; first generation cephalosporins; fourth generation cephalosporins; gamma-aminobutyric acid analogs; gamma-aminobutyric acid reuptake inhibitors; gastrointestinal agents; genitourinary tract agents; GI stimulants; glucocorticoids; glucose elevating agents; glycopeptide antibiotics; glycoprotein platelet inhibitors; glycylcyclines; gonadotropin releasing hormones; gonadotropin-releasing hormone antagonists; gonadotropins; group I antiarrhythmics; group II antiarrhythmics; group III antiarrhythmics; group IV antiarrhythmics; group V antiarrhythmics; growth hormone receptor blockers; growth hormones; guanylate cyclase-C agonists; H. pylori eradication agents; H2 antagonists; hedgehog pathway inhibitorshematopoietic stem cell mobilizer; heparin antagonists; heparins; HER2 inhibitors; histone deacetylase inhibitors; hormones; hormones/antineoplastics; hydantoin anticonvulsants; hydrazide derivatives; immune globulins; immunologic agents; immunostimulants; immunosuppressive agents; incretin mimetics; inotropic agents; insulin; insulin-like growth factor; integrase strand transfer inhibitor; interferons; interleukin inhibitors; interleukins; ketolides; leprostatics; leukotriene modifiers; lincomycin derivatives; loop diuretics; lymphatic staining agents; lysosomal enzymes; macrolide derivatives; macrolides; mast cell stabilizers; meglitinides; metabolic agents; methylxanthines; mineralocorticoids; mitotic inhibitors; monoamine oxidase inhibitors; mTOR inhibitors; mucolytics; multikinase inhibitors; muscle relaxants; mydriatics; narcotic analgesics; natural penicillins; neuraminidase inhibitors; neuromuscular blocking agents; neuronal potassium channel openers; next generation cephalosporins; nicotinic acid derivatives; NNRTIs; non-cardioselective beta blockers; non-sulfonylureas; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors (NRTIs); oxazolidinedione anticonvulsants; parathyroid hormone and analogs; penicillinase resistant penicillins; penicillins; peripheral opioid receptor antagonists; peripheral vasodilators; peripherally acting antiobesity agents; phenothiazine antiemetics; phenothiazine antipsychotics; phenylpiperazine antidepressants; plasma expanders; platelet aggregation inhibitors; platelet-stimulating agents; polyenes; potassium-sparing diuretics; probiotics; progesterone receptor modulators; progestins; prolactin inhibitors; prostaglandin D2 antagonists; protease inhibitors; proteasome inhibitors; proton pump inhibitors; psoralens; psychotherapeutic agents; purine nucleosides; pyrrolidine anticonvulsants; quinolones; recombinant human erythropoietins; renin inhibitors; respiratory agents; rifamycin derivatives; salicylates; sclerosing agents; second generation cephalosporins; selective estrogen receptor modulators; selective immunosuppressants; selective phosphodiesterase-4 inhibitors; selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; serotoninergic neuroenteric modulators; sex hormone combinations; sex hormones; SGLT-2 inhibitors; skeletal muscle relaxants; smoking cessation agents; somatostatin and somatostatin analogs; statins; streptomyces derivatives; succinimide anticonvulsants; sulfonamides; sulfonylureas; synthetic ovulation stimulants; tetracyclic antidepressants; tetracyclines; therapeutic radiopharmaceuticals; therapeutic vaccines; thiazide diuretics; thiazolidinediones; thioxanthenes; third generation cephalosporins; thrombin inhibitors; thrombolytics; thyroid drugs; TNF alfa inhibitors; tocolytic agents; triazine anticonvulsants; tricyclic antidepressants; trifunctional monoclonal antibodies; urea anticonvulsants; urea cycle disorder agents; urinary anti-infectives; urinary antispasmodics; vasodilators; vasopressin antagonists; vasopressors; VEGF/VEGFR inhibitors; viral vaccines. 14. A method of functionalizing a graphene substrate, wherein the method comprises the steps of: a) obtaining a graphene substrate that has edge regions and non-edge regions, wherein the non-edge regions comprise epoxy moieties; b) reacting the epoxy moieties with a Nu-M, wherein Nu is a nucleophilic moiety and M is an attached organic or inorganic moiety, thereby functionalizing the graphene substrate. 15. The method according to claim 14, wherein Nu is NH.sub.2, and wherein M is an attached organic moiety, and wherein the organic moiety is selected from a group of organic moieties consisting of: an antibody; a linking group attached to an antibody; an antibody fragment; a linking group attached to an antibody fragment; a linking group attached to an aptamer; a protein; a linking group attached to a protein; an oligopeptide; a linking group attached to an oligopeptide; a linking group attached to an oligosaccharide; a large molecule therapeutic; a linking group attached to a large molecule therapeutic; a small molecule therapeutic; a linking group attached to a small molecule therapeutic. 16. The method according to claim 15, wherein the organic molecule is a linking group attached to a protein, and wherein the protein is selected from a group consisting of: Insulin; Pramlintide; Growth hormone; Mecasermin; Factor VIII; Factor IX; Antithrombin III; Protein C; B-Gluco-cerebrosidase; Alglucosidase-.alpha.; Laronidase; Idursulphase; Galsulphase; Agalsidase-.beta.; A-1-Proteinase inhibitor; Lactase; Lipase; Amylase; Protease; Adenosine deaminase; Human albumin; Erythropoietin; Darbepoetin-.alpha.; Filgrastim; Sargramostim; Oprelvekin; Human follicle-stimulating hormone; Human chorionic gonadotropin; Lutropin-.alpha.; Type I .alpha.-interferon; Interferon-.alpha.2a; Interferon-.alpha.2b; Interferon-.alpha.n3; Interferon-.beta.1a; Interferon-.beta.1b; Interferon-.gamma.1b; Aldesleukin; Alteplase; Reteplase; Tenecteplase; Urokinase; Factor VIIa; Drotrecogin-.alpha.; Salmon calcitonin; Teriparatide; Exenatide; Octreotide; Dibotermin-.alpha.; Recombinant human bone morphogenic protein 7; Histrelin; Palifermin; Becaplermin; Trypsin; Nesiritide; Botulinum toxin type A; Botulinum toxin type B; Collagenase; Human deoxy-ribonuclease I; Hyaluronidase; Papain; L-Asparaginase; Rasburicase; Lepirudin; Bivalirudin; Streptokinase; Anistreplase; Bevacizumab; Cetuximab; Panitumumab; Alemtuzumab; Rituximab; Trastuzumab; Abtacept; Anakinra; Adalimumab; Etanercept; Infliximab; Alefacept; Efalizumab; Natalizumab; Eculizumab; Antithymocyte globulin; Basiliximab; Daclizumab; Muromonab-CD3; Omalizumab; Palivizumab; Enfuvirtide; Abciximab; Pegvisomant; Crotalidae polyvalent immune Fab; Digoxin immune serum Fab; Ranibizumab; Denileukin diftitox; Ibritumomab tiuxetan; Gemtuzumab ozogamicin; Tositumomab; DNA polymerase. 17. The method according to claim 16, wherein the functionalized graphene substrate has a population of organic molecules at the non-edge regions of at least 1 per 30,000 nm.sup.2. 18. The method according to claim 17, wherein the functionalized graphene substrate has a population of organic molecules at the non-edge regions of at least 1 per 10,000 nm.sup.2. 19. A method of functionalizing a graphene substrate, wherein the method comprises the steps of: a) obtaining a graphene substrate that has edge regions and non-edge regions, wherein the non-edge regions comprise hydroxy moieties; b) reacting the hydroxyl moieties with a E-M, wherein E is an electrophilic moiety and M is an attached organic or inorganic moiety, thereby functionalizing the graphene substrate. 20. The method according to claim 19, wherein EM is OCN-Protein, wherein the N atom is part of the protein, and wherein the protein is selected from a group of proteins consisting of: Insulin; Pramlintide; Growth hormone; Mecasermin; Factor VIII; Factor IX; Antithrombin III; Protein C; B-Gluco-cerebrosidase; Alglucosidase-.alpha.; Laronidase; Idursulphase; Galsulphase; Agalsidase-.beta.; A-1-Proteinase inhibitor; Lactase; Lipase; Amylase; Protease; Adenosine deaminase; Human albumin; Erythropoietin; Darbepoetin-.alpha.; Filgrastim; Sargramostim; Oprelvekin; Human follicle-stimulating hormone; Human chorionic gonadotropin; Lutropin-.alpha.; Type I .alpha.-interferon; Interferon-.alpha.2a; Interferon-.alpha.2b; Interferon-.alpha.n3; Interferon-.beta.1a; Interferon-.beta.1b; Interferon-.gamma.1b; Aldesleukin; Alteplase; Reteplase; Tenecteplase; Urokinase; Factor VIIa; Drotrecogin-.alpha.; Salmon calcitonin; Teriparatide; Exenatide; Octreotide; Dibotermin-.alpha.; Recombinant human bone morphogenic protein 7; Histrelin; Palifermin; Becaplermin; Trypsin; Nesiritide; Botulinum toxin type A; Botulinum toxin type B; Collagenase; Human deoxy-ribonuclease I; Hyaluronidase; Papain; L-Asparaginase; Rasburicase; Lepirudin; Bivalirudin; Streptokinase; Anistreplase; Bevacizumab; Cetuximab; Panitumumab; Alemtuzumab; Rituximab; Trastuzumab; Abtacept; Anakinra; Adalimumab; Etanercept; Infliximab; Alefacept; Efalizumab; Natalizumab; Eculizumab; Antithymocyte globulin; Basiliximab; Daclizumab; Muromonab-CD3; Omalizumab; Palivizumab; Enfuvirtide; Abciximab; Pegvisomant; Crotalidae polyvalent immune Fab; Digoxin immune serum Fab; Ranibizumab; Denileukin diftitox; Ibritumomab tiuxetan; Gemtuzumab ozogamicin; Tositumomab; DNA polymerase. 21. The method according to claim 20, wherein the functionalized graphene substrate has a population of organic molecules at the non-edge regions of at least 1 per 30,000 nm.sup.2. 22. The method according to claim 21, wherein the functionalized graphene substrate has a population of organic molecules at the non-edge regions of at least 1 per 10,000 nm.sup.2. 23. A method of functionalizing a graphene substrate, wherein the method comprises the steps of: 1. obtaining a graphene substrate that has edge regions and non-edge regions; 2. reacting the substrate with a molecule that comprises a histidine, arginine, lysine or cationic tag covalently attached to it thereby providing a functionalized graphene substrate, wherein molecules are non-covalently attached to the non-edge regions of the substrate. 24. The method according to claim 23, wherein the molecule is a protein, and wherein the protein is selected from a group of proteins consisting of: Insulin; Pramlintide; Growth hormone; Mecasermin; Factor VIII; Factor IX; Antithrombin III; Protein C; B-Gluco-cerebrosidase; Alglucosidase-.alpha.; Laronidase; Idursulphase; Galsulphase; Agalsidase-.beta.; A-1-Proteinase inhibitor; Lactase; Lipase; Amylase; Protease; Adenosine deaminase; Human albumin; Erythropoietin; Darbepoetin-.alpha.; Filgrastim; Sargramostim; Oprelvekin; Human follicle-stimulating hormone; Human chorionic gonadotropin; Lutropin-.alpha.; Type I .alpha.-interferon; Interferon-.alpha.2a; Interferon-.alpha.2b; Interferon-.alpha.n3; Interferon-.beta.1a; Interferon-.beta.1b; Interferon-.gamma.1b; Aldesleukin; Alteplase; Reteplase; Tenecteplase; Urokinase; Factor VIIa; Drotrecogin-.alpha.; Salmon calcitonin; Teriparatide; Exenatide; Octreotide; Dibotermin-.alpha.; Recombinant human bone morphogenic protein 7; Histrelin; Palifermin; Becaplermin; Trypsin; Nesiritide; Botulinum toxin type A; Botulinum toxin type B; Collagenase; Human deoxy-ribonuclease I; Hyaluronidase; Papain; L-Asparaginase; Rasburicase; Lepirudin; Bivalirudin; Streptokinase; Anistreplase; Bevacizumab; Cetuximab; Panitumumab; Alemtuzumab; Rituximab; Trastuzumab; Abtacept; Anakinra; Adalimumab; Etanercept; Infliximab; Alefacept; Efalizumab; Natalizumab; Eculizumab; Antithymocyte globulin; Basiliximab; Daclizumab; Muromonab-CD3; Omalizumab; Palivizumab; Enfuvirtide; Abciximab; Pegvisomant; Crotalidae polyvalent immune Fab; Digoxin immune serum Fab; Ranibizumab; Denileukin diftitox; Ibritumomab tiuxetan; Gemtuzumab ozogamicin; Tositumomab; DNA polymerase. 25. The method according to claim 24, wherein the functionalized graphene substrate has a population of organic molecules at the non-edge regions of at least 1 per 30,000 nm.

Details for Patent 9,402,910

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	01/15/1974		2033-07-12
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	12/27/1984		2033-07-12
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/15/1985		2033-07-12
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/16/1990		2033-07-12