DOCSLIB.ORG

United States Patent (19) 11 Patent Number: 6,068,830 Diamandis Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent (19) 11 Patent Number: 6,068,830 Diamandis Et Al US00606883OA United States Patent (19) 11 Patent Number: 6,068,830 Diamandis et al. (45) Date of Patent: May 30, 2000 54) LOCALIZATION AND THERAPY OF FOREIGN PATENT DOCUMENTS NON-PROSTATIC ENDOCRINE CANCER 0217577 4/1987 European Pat. Off.. WITH AGENTS DIRECTED AGAINST 0453082 10/1991 European Pat. Off.. PROSTATE SPECIFIC ANTIGEN WO 92/O1936 2/1992 European Pat. Off.. WO 93/O1831 2/1993 European Pat. Off.. 75 Inventors: Eleftherios P. Diamandis, Toronto; Russell Redshaw, Nepean, both of OTHER PUBLICATIONS Canada Clinical BioChemistry vol. 27, No. 2, (Yu, He et al), pp. 73 Assignee: Nordion International Inc., Canada 75-79, dated Apr. 27, 1994. Database Biosis BioSciences Information Service, AN 21 Appl. No.: 08/569,206 94:393008 & Journal of Clinical Laboratory Analysis, vol. 8, No. 4, (Yu, He et al), pp. 251-253, dated 1994. 22 PCT Filed: Jul. 14, 1994 Bas. Appl. Histochem, Vol. 33, No. 1, (Papotti, M. et al), 86 PCT No.: PCT/CA94/00392 Pavia pp. 25–29 dated 1989. S371 Date: Apr. 11, 1996 Primary Examiner Yvonne Eyler S 102(e) Date: Apr. 11, 1996 Attorney, Agent, or Firm-Banner & Witcoff, Ltd. 87 PCT Pub. No.: WO95/02424 57 ABSTRACT It was discovered that prostate-specific antigen is produced PCT Pub. Date:Jan. 26, 1995 by non-proStatic endocrine cancers. It was further discov 30 Foreign Application Priority Data ered that non-prostatic endocrine cancers with Steroid recep tors can be stimulated with Steroids to cause them to produce Jul. 14, 1993 GB United Kingdom ................... 93.14623 PSA either initially or at increased levels. This invention 51) Int. Cl." .......................... A61K 51/00; A61K 49/00; relates to the imaging of non-prostatic endocrine cancers by G01N 31/00; G01N 33/48 labelled biological binding units which bind to prostate 52 U.S. Cl. .................... 424/9.34; 424/1.49; 424/9.323; Specific antigen in an imaging procedure, Such as, radioim 435/723; 436/64 aging or magnetic resonance imaging. Further, the PSA 58 Field of Search .......................... 435/7.23; 424/1.49, binding units may be constructed to deliver a toxic agent, 424/9.34, 9.323; 436/64 Such as a radioisotope, toxin or a drug to provide endocrine cancer therapy. Another aspect of the invention is passive 56) References Cited immunotherapy against endocrine cancers by treatment with PSA-binding units. U.S. PATENT DOCUMENTS 5,162,504 11/1992 Horoszewicz ........................ 530/388.2 7 Claims, 4 Drawing Sheets U.S. Patent May 30, 2000 Sheet 1 of 4 6,068,830 6 A Free PSA 2 45000 E 5 CS d S 4 35000 g 35 25000 1 15000 SD O o O 1 O 20 30 40 50 60 5000 Fraction Number F. G. A. B Free PSA 45OOO ACT-PSA t 35OOO 25000 l i 15000 adtw. 5OOO 1O 20 30 40 50 60 Fraction Number F. G. B. U.S. Patent May 30, 2000 Sheet 2 of 4 6,068,830 PSA 4.4 U.S. Patent May 30, 2000 Sheet 3 of 4 6,068,830 1O 1. S 1 O) 2 P CC { ... 1 O1 -11 -10 -9 -8 -7 -6 Log(Steroid Concentration,mol/L) F. G. 3. U.S. Patent May 30, 2000 Sheet 4 of 4 6,068,830 & - - - - - - - - - - - - - - - - & & S.& 6,068,830 1 2 LOCALIZATION AND THERAPY OF NON Direct approaches to radionuclide imaging include radio PROSTATIC ENDOCRINE CANCER WITH labelled chemotherapeutic agents, simple ionic Substances, AGENTS DIRECTED AGAINST PROSTATE metabolite imaging, immunologic and receptor imaging. SPECIFIC ANTIGEN The use of radiolabelled chemotherapeutic agents, Such as bleomycin, have not demonstrated clinical value (14). ''Ga FIELD OF THE INVENTION citrate is the most commonly used simple ionic tracer for This invention relates to the localization and therapy of tumor imaging, however it localizes in other pathologies and non-prostatic endocrine cancers by agents that have been is non specific (15, 16, 17, 18). Metabolite imaging carried constructed to target prostate specific antigen (PSA). out with positron emitting radionuclides such as F fluorodeoxyglucose, 'C-methionine and 'C-thymidine BACKGROUND OF THE INVENTION provides tumor metabolism information that has been shown Cancer of the breast is the most common cause of cancer to be clinically valuable for disease staging (19, 20, 21). death in middle aged women in Europe and North America The receptor imaging of breast cancer has been attempted and both its incidence and mortality are on the increase by Several approaches. Spicer et al. (22) and Hochberg (23) (1-5). The predominant indications for breast tumor imag 15 and others (24-29) have developed radiolabelled estradiols ing are: detecting the presence of tumor, localizing Sites of and have been able to demonstrate imaging in estrogen disease, and following the effects of therapy (6). Trends in receptor positive breast cancers. It has been postulated that Scintigraphic imaging have been towards developing imag a therapeutic response could result with Auger electrons ing pharmaceuticals to provide quantitative information on from 'I or 'I radiolabelled estradiols (30,31), or from B the pathophysiological characteristics of a tumor, Such as its emitting radioisotopes such as Re conjugated to proges anaplasticity, or likely response to a given therapy (7). For terone (32). A problem with receptor based imaging is the example, to determine Via Scintigraphic imaging how a interference that estrogen receptor antagonists, Such as patients breast cancer will respond to the administration of a growth Suppressor, Such as Somatostatin, or the estrogen tamoxifen, may have in the clinical environment. receptor antagonist tamoxifen (8). Diamandis in PCT Appli 25 It is known that proteins, Such as antibodies, can be cation CA 94/00267 has shown that the presence of PSA in developed against Specific antigens that are either produced breast tumors, as measured by in vitro methods, has prog or associated with tumors, can be used to localize tumors. nostic value. Thus, imaging of these tumors may not only U.S. Pat. No. 3,927,193 to Hansen et al. (33) discloses a reveal occult disease, but may also provide clinically valu process whereby antibodies to carcinoembryonic antigen able pathophysiological information. (CEA) and labelled with 'I and "I were used to image the location of tumors present in hamsters. From this work it Tumor imaging is commonly carried out using a gamma was proposed that the location of a tumor in a human could emitting radionuclide conjugate and a Scintillation gamma be determined by in Vivo administration of a parenteral camera, or with a positron emitting radiopharmaceutical and Solution containing an antibody-radioisotope conjugate fol a positron or PET camera, or with a magnetopharmaceutical lowed by imaging by a gamma camera. Goldenberg et al. and a magnetic resonance imaging device. The Scintillation 35 camera, also known as an Anger camera, consists of a reported Success in clinical trials of tumor detection and detector head, and a display console. The Anger camera head localization by Scintillation Scanning of patients that is composed of Sodium iodide crystals that absorb gamma received radiolabelled antibodies to CEA (34). rays and emits the absorbed energy as flashes of light Based on the original work of Milstein and Kohler (35), Scintillations that are proportional in brightness to the energy 40 monoclonal antibodies have been developed against a vari absorbed. In a gamma camera the Sodium iodide crystals are ety of tumour antigens such as CA 19.9, CA 125, melanoma coupled to photomultiplier tubes that convert light pulses asSociated antigens, TAG 72, C. fetal protein, ferritin, into electronic pulses. These voltages are translated via a choriogonadotropin, prostatic acid phosphatase, and PSA for computing circuit to a cathode ray tube. The data from the radioimmunoimaging and therapy. camera head may be in either analog or digital form that can 45 Several investigators have reported on the development of be stored in a computer and can reconstruct the data to monoclonal antibodies against epitopes of various malignant provide an image. Single-photon emission computed tomog prostate cell components (36, 37, 38, 39, 40). Moveover, raphy (SPECT) imaging involves the use of a gamma PSA was purified and well characterized and found to have Scintillation camera where multiple images, typically a molecular weight in the range of 34,000 (41). PSA is used encompassing 180 or 360, around the body are taken and 50 widely as a tumor marker for in vitro based analyses for the computer issued to reconstruct multiple tomograms in diagnostic and monitoring purposes of prostatic carcinoma. coronal, Sagittal, and transverse projections. In PET imaging U.S. Pat. No. 5,162,504 describes monoclonal antibodies the positron radionuclide collides with an electron causing that have been developed to recognize malignant prostate annihilation of the particles and creating two photons that epithelium. These antibodies were developed as diagnostic travel in 180 opposite directions. The PET system is 55 and prognostic tools for the detection of cancer of the designed to capture opposite sides and register the count at prostate, not as embodies in this invention, for the detection precisely the same time. A computer is used to manipulate of cancers not associated with the prostate. Until the dis the data and then reconstruct a croSS Sectional image from covery reported by Diamandis in International Application this information. PCT CA94/00267, it was thought that PSA only occurred in There are a number of approaches to breast tumor imag 60 men and was only produced by prostate tissue. ing that may be divided into two groups: indirect and direct. To image breast tumors researchers have developed anti Indirect techniques, are generally utilized to locate meta bodies directed against TAG 72, CA-3, CEA, EGF-R, Static disease by recognizing the Secondary effects of tumor LASA-P, and other glycoproteins associated with breast within an organ System.
Load more

Recommended publications
  • United States July 2016 2 Table of Contents
    Deuterium Labelled Compounds United States July 2016 2 Table of Contents International Distributors 3 Corporate Overview 4 General Information 5 Pricing and Payment 5 Quotations 5 Custom Synthesis 5 Shipping 5 Quality Control 6 Quotations 6 Custom Synthesis 6 Shipping 6 Quality Control 6 Chemical Abstract Service Numbers 6 Handling Hazardous Compounds 6 Our Products are Not Intended for Use in Humans 7 Limited Warranty 7 Packaging Information 7 Alphabetical Listings 8 Stock Clearance 236 Products by Category 242 n-Alkanes 243 α-Amino Acids, N-Acyl α-Amino Acids, N-t-BOC Protected α-Amino Acid 243 and N-FMOC Protected α-Amino Acids Buffers and Reagents for NMR Studies 245 Detergents 245 Environmental Standards 246 Fatty Acids and Fatty Acid Esters 249 Flavours and Fragrances 250 Gases 253 Medical Research Products 254 Nucleic Acid Bases and Nucleosides 255 Pesticides and Pesticide Metabolites 256 Pharmaceutical Standards 257 Polyaromatic Hydrocarbons (PAHs), Alkyl-PAHs, Amino-PAHs, 260 Hydroxy-PAHs and Nitro-PAHs Polychlorinated Biphenyls (PCBs) 260 Spin Labels 261 Steroids 261 3 International Distributors C Beijng Zhenxiang H EQ Laboratories GmbH Australia K Technology Company Graf-von-Seyssel-Str. 10 Rm. 15A01, Changyin Bld. 86199 Augsburg Austria H No. 88, YongDingLu Rd. Germany Beijing 100039 Tel.: (49) 821 71058246 Belgium J China Fax: (49) 821 71058247 Tel.: (86) 10-58896805 [email protected] China C Fax: (86) 10-58896158 www.eqlabs.de Czech Republic H [email protected] Germany, Austria, China Czech Republic, Greece, Denmark I Hungary,
    [Show full text]
  • 2006 Steroids Report
    2006 Steroids Report Prepared by the Steroids Working Group United States Sentencing Commission March 2006 REPORT OF THE STEROIDS POLICY TEAM I. SUMMARY Congress passed the Anabolic Steroid Control Act of 2004 (the Act)1 to “address the abuse of steroids by athletes and, especially, by youngsters and teenagers.”2 The Act directed the United States Sentencing Commission (the “Commission” or “USSC”) to: (1) review the federal sentencing guidelines with respect to anabolic steroids; (2) consider amending the federal sentencing guidelines to provide for increased penalties with respect to offenses involving anabolic steroids in a manner that reflects the seriousness of such offenses and the need to deter anabolic steroid trafficking and abuse; and (3) take such other action that the Commission considers necessary to carry out this section.3 The Commission added consideration of steroids offenses to its list of priorities for its 2004-2005 amendment cycle, in recognition of the serious concern over these offenses and the need to fulfill the congressional directive contained in the Act. This report sets forth legislative and guideline history pertaining to steroids offenses, discusses the Commission’s response to legislation, and updates the findings in the Commission’s 1990 Steroids Report. II. BACKGROUND ON STEROIDS AND CURRENT PENALTY STRUCTURE Steroids is a broad term used to describe a variety of individual drugs that are delivered to end users primarily in two major forms: injectable liquid held in vials and pills.4 Steroids are typically used in various combinations with a user often combining four or five different types of 1 Anabolic Steroid Control Act of 2004, Pub.
    [Show full text]
  • IJCB 42B(1) 166-172.Pdf
    Indian Journal of Chemistry Vol. 42B, January 2003, pp. 166-172 Synthesis and biological activity of 16-arylidene derivatives of estrone and estrone methyl ether Maninder Minu* & Dharam Paul lindal University In 5titutc of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India and G Leclercq & M Borras institut Jules Bordet, Association Hospitaliere de Bruxelles. Centre des Tumeurs de I'ULB, Rue Heger-Bordet 1- 1000, Belgiulll Received 24 April 200 I .. accepted (revised) 20 March 2002 The synthesis of 16-arylidene derivatives 3, 4, S, 6, 7. 8. 9, 10, 11, 12, 13, 14 and IS is described. These compounds have been tested at NCI, Bethesda, for their antineoplastic acti vity against the cell panel consisting of 60-ce!l lines and th e compounds 3, 4, S, 6 and 7 have also been tested for their ill vitro estrogenic / antiestrogenic activity; induction of ERE­ dependent luciferase inductio n was measured (MvLN celis). The formation of active steroids by aromatase has It was conceived that selective inhibitors of aroma­ been considered to play an important role in the de­ tase might be useful as a pharmacological tool to de­ velopment of human breast carcinoma t, at least one­ vice successful treatment approach for the hormonal third of all breast cancers establishing that. the estro­ dependent breast cancer. Our efforts were focused on gen-dependent carcinoma regresses following estro­ designing estrogen and estrogen methyl ether deriva­ 2 gen deprivation . In the postmenopausal women, the tives that might inhibit or possess antiestrogenic activ­ production of estrogen takes place in peripheral tissue ity. From these efforts, several 16-arylidine deriva­ 3 from inactive precursors by the action of aromatase .
    [Show full text]
  • Critical Role of Oxidative Stress in Estrogen-Induced Carcinogenesis
    Critical role of oxidative stress in estrogen-induced carcinogenesis Hari K. Bhat*†, Gloria Calaf‡, Tom K. Hei*‡, Theresa Loya§, and Jaydutt V. Vadgama¶ *Department of Environmental Health Sciences, Mailman School of Public Health, 60 Haven Avenue-B1, Columbia University, New York, NY 10032; ‡Center for Radiological Research, Columbia University, New York, NY 10032; and Departments of §Pathology and ¶Medicine, Charles Drew University, Los Angeles, CA 90059 Communicated by Donald C. Malins, Pacific Northwest Research Institute, Seattle, WA, December 27, 2002 (received for review August 22, 2002) Mechanisms of estrogen-induced tumorigenesis in the target quinones generates oxidative stress and potentially harmful free organ are not well understood. It has been suggested that oxida- radicals that are postulated to be required for the carcinogenic tive stress resulting from metabolic activation of carcinogenic process, and analogous to the metabolic activation of hydrocar- estrogens plays a critical role in estrogen-induced carcinogenesis. bons and other nonsteroidal estrogen carcinogens (9, 19–22). We We tested this hypothesis by using an estrogen-induced hamster have investigated the role of oxidative stress in estrogen carci- renal tumor model, a well established animal model of hormonal nogenesis by using a well established hamster renal tumor model carcinogenesis. Hamsters were implanted with 17␤-estradiol (␤E2), that shares several characteristics with human breast and uterine 17␣-estradiol (␣E2), 17␣-ethinylestradiol (␣EE), menadione, a com- cancers, pointing to a common mechanistic origin (6, 9, 23). bination of ␣E2 and ␣EE, or a combination of ␣EE and menadione Different estrogens used in the present study differ in their for 7 months.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • Novel Derivatives of Bio-Affecting Phenolic Compounds and Pharmaceutical Composition Containing Them
    Europaisches Patentamt European Patent Office © Publication number: 0046 270 A1 Office europeen des brevets ™ EUROPEAN PATENT APPLICATION @ Application number: 81106277.7 © Int. CI.3: C 07 C 103/78, C 07 C 93/26, C 07 C 69/24, C 07 C 1 53/07, @ Date of filing: 12.08.81 C07C 69/28 // C07C1 25/065 <§) Priority: 13.08.80 US 177825 © Applicant: INTERx RESEARCH CORPORATION, 2201 West 21 st Street, Lawrence Kansas 66044 (US) © I nventor : Bodor, Nicholas S., 31 5 Southwest 91 st Street, ® Dateofpublicationofapplication:24.02.82 S^^S^mHariMBM Bulletin m/b Terrace, Gainesville, Florida 32605 (US) Inventor: Pogany, Stefano A., 520 Louisiana Street, Lawrence Kansas 66044 (US) @ Designated Contracting States : AT BE CH DE FR GB IT ® Representative: Abitz, Walter, Dr.-lng. et al, Abitz, Mori, LI LU NL SE Gritschneder P.O. Box 86 01 09, D-8000 Munchen 86 (DE) Novel derivatives of bio-affecting phenolic compounds and pharmaceutical composition containing them. Novel@ Novel transient prodrug forms of bio-affecting phe- amyl, CH2ONO2,CH2ON02, -CH2OCOR2 or any non-heterocyclic nolic compounds are selected from the group consisting of member of the group defined by R2Rz above; and n.isn is at least those having the structural formula (I): one and equals the total number of phenolic hydroxyl functions comprising the non-steroidal bioaffecting phenol o etherified via a R2COXCH(R3)0-moiety; those having the structural formula (II): R2-C-X-CH-0- (I) I O R, II R2-C-X-CH-0- -RM-i-O-C-R2 (II) wherein X is O, S or NR5 wherein R5 is hydrogen or lower alkyl;alky!;
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2020 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT, CPTPT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • Pp375-430-Annex 1.Qxd
    ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay,
    [Show full text]
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [Show full text]
  • NDA/BLA Multi-Disciplinary Review and Evaluation
    NDA/BLA Multi-disciplinary Review and Evaluation NDA 214154 Nextstellis (drospirenone and estetrol tablets) NDA/BLA Multi-Disciplinary Review and Evaluation Application Type NDA Application Number(s) NDA 214154 (IND 110682) Priority or Standard Standard Submit Date(s) April 15, 2020 Received Date(s) April 15, 2020 PDUFA Goal Date April 15, 2021 Division/Office Division of Urology, Obstetrics, and Gynecology (DUOG) / Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM) Review Completion Date April 15, 2021 Established/Proper Name drospirenone and estetrol tablets (Proposed) Trade Name Nextstellis Pharmacologic Class Combination hormonal contraceptive Applicant Mayne Pharma LLC Dosage form Tablet Applicant proposed Dosing x Take one tablet by mouth at the same time every day. Regimen x Take tablets in the order directed on the blister pack. Applicant Proposed For use by females of reproductive potential to prevent Indication(s)/Population(s) pregnancy Recommendation on Approval Regulatory Action Recommended For use by females of reproductive potential to prevent Indication(s)/Population(s) pregnancy (if applicable) Recommended Dosing x Take one pink tablet (drospirenone 3 mg, estetrol Regimen anhydrous 14.2 mg) by mouth at the same time every day for 24 days x Take one white inert tablet (placebo) by mouth at the same time every day for 4 days following the pink tablets x Take tablets in the order directed on the blister pack 1 Reference ID: 4778993 NDA/BLA Multi-disciplinary Review and Evaluation NDA 214154 Nextstellis (drospirenone and estetrol tablets) Table of Contents Table of Tables .................................................................................................................... 5 Table of Figures ................................................................................................................... 7 Reviewers of Multi-Disciplinary Review and Evaluation ...................................................
    [Show full text]
  • Part I Biopharmaceuticals
    1 Part I Biopharmaceuticals Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 3 1 Analogs and Antagonists of Male Sex Hormones Robert W. Brueggemeier The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, Ohio 43210, USA 1Introduction6 2 Historical 6 3 Endogenous Male Sex Hormones 7 3.1 Occurrence and Physiological Roles 7 3.2 Biosynthesis 8 3.3 Absorption and Distribution 12 3.4 Metabolism 13 3.4.1 Reductive Metabolism 14 3.4.2 Oxidative Metabolism 17 3.5 Mechanism of Action 19 4 Synthetic Androgens 24 4.1 Current Drugs on the Market 24 4.2 Therapeutic Uses and Bioassays 25 4.3 Structure–Activity Relationships for Steroidal Androgens 26 4.3.1 Early Modifications 26 4.3.2 Methylated Derivatives 26 4.3.3 Ester Derivatives 27 4.3.4 Halo Derivatives 27 4.3.5 Other Androgen Derivatives 28 4.3.6 Summary of Structure–Activity Relationships of Steroidal Androgens 28 4.4 Nonsteroidal Androgens, Selective Androgen Receptor Modulators (SARMs) 30 4.5 Absorption, Distribution, and Metabolism 31 4.6 Toxicities 32 Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 4 Analogs and Antagonists of Male Sex Hormones 5 Anabolic Agents 32 5.1 Current Drugs on the Market 32 5.2 Therapeutic Uses and Bioassays
    [Show full text]
  • A New Robust Technique for Testing of Glucocorticosteroids in Dogs and Horses Terry E
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 A new robust technique for testing of glucocorticosteroids in dogs and horses Terry E. Webster Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Veterinary Toxicology and Pharmacology Commons Recommended Citation Webster, Terry E., "A new robust technique for testing of glucocorticosteroids in dogs and horses" (2007). Retrospective Theses and Dissertations. 15029. https://lib.dr.iastate.edu/rtd/15029 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. A new robust technique for testing of glucocorticosteroids in dogs and horses by Terry E. Webster A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Toxicology Program o f Study Committee: Walter G. Hyde, Major Professor Steve Ensley Thomas Isenhart Iowa State University Ames, Iowa 2007 Copyright © Terry Edward Webster, 2007. All rights reserved UMI Number: 1446027 Copyright 2007 by Webster, Terry E. All rights reserved. UMI Microform 1446027 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii DEDICATION I want to dedicate this project to my wife, Jackie, and my children, Shauna, Luke and Jake for their patience and understanding without which this project would not have been possible.
    [Show full text]