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ENSG Gene Encodes Effector TCR Pathway Costimulation Inhibitory/Exhaustion Synapse/Adhesion Chemokines/Receptors
ENSG Gene Encodes Effector TCR pathway Costimulation Inhibitory/exhaustion Synapse/adhesion Chemokines/receptors ENSG00000111537 IFNG IFNg x ENSG00000109471 IL2 IL-2 x ENSG00000232810 TNF TNFa x ENSG00000271503 CCL5 CCL5 x x ENSG00000139187 KLRG1 Klrg1 x ENSG00000117560 FASLG Fas ligand x ENSG00000121858 TNFSF10 TRAIL x ENSG00000134545 KLRC1 Klrc1 / NKG2A x ENSG00000213809 KLRK1 Klrk1 / NKG2D x ENSG00000188389 PDCD1 PD-1 x x ENSG00000117281 CD160 CD160 x x ENSG00000134460 IL2RA IL-2 receptor x subunit alpha ENSG00000110324 IL10RA IL-10 receptor x subunit alpha ENSG00000115604 IL18R1 IL-18 receptor 1 x ENSG00000115607 IL18RAP IL-18 receptor x accessory protein ENSG00000081985 IL12RB2 IL-12 receptor x beta 2 ENSG00000186810 CXCR3 CXCR3 x x ENSG00000005844 ITGAL CD11a x ENSG00000160255 ITGB2 CD18; Integrin x x beta-2 ENSG00000156886 ITGAD CD11d x ENSG00000140678 ITGAX; CD11c x x Integrin alpha-X ENSG00000115232 ITGA4 CD49d; Integrin x x alpha-4 ENSG00000169896 ITGAM CD11b; Integrin x x alpha-M ENSG00000138378 STAT4 Stat4 x ENSG00000115415 STAT1 Stat1 x ENSG00000170581 STAT2 Stat2 x ENSG00000126561 STAT5a Stat5a x ENSG00000162434 JAK1 Jak1 x ENSG00000100453 GZMB Granzyme B x ENSG00000145649 GZMA Granzyme A x ENSG00000180644 PRF1 Perforin 1 x ENSG00000115523 GNLY Granulysin x ENSG00000100450 GZMH Granzyme H x ENSG00000113088 GZMK Granzyme K x ENSG00000057657 PRDM1 Blimp-1 x ENSG00000073861 TBX21 T-bet x ENSG00000115738 ID2 ID2 x ENSG00000176083 ZNF683 Hobit x ENSG00000137265 IRF4 Interferon x regulatory factor 4 ENSG00000140968 IRF8 Interferon -
Old and New Challenges in Uveitis Associated with Behçet's Disease
Journal of Clinical Medicine Review Old and New Challenges in Uveitis Associated with Behçet’s Disease Julie Gueudry 1,* , Mathilde Leclercq 2, David Saadoun 3,4,5 and Bahram Bodaghi 6 1 Department of Ophthalmology, Hôpital Charles Nicolle, F-76000 Rouen, France 2 Department of Internal Medicine, Hôpital Charles Nicolle, F-76000 Rouen, France; [email protected] 3 Department of Internal Medicine and Clinical Immunology, AP-HP, Centre National de Références Maladies Autoimmunes et Systémiques Rares et Maladies Autoinflammatoires Rares, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France; [email protected] 4 Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR S 959, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France 5 Biotherapy (CIC-BTi), Hôpital Pitié-Salpêtrière, AP-HP, F-75651 Paris, France 6 Department of Ophthalmology, IHU FOReSIGHT, Sorbonne-AP-HP, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France; [email protected] * Correspondence: [email protected]; Tel.: +33-2-32-88-80-57 Abstract: Behçet’s disease (BD) is a systemic vasculitis disease of unknown origin occurring in young people, which can be venous, arterial or both, classically occlusive. Ocular involvement is particularly frequent and severe; vascular occlusion secondary to retinal vasculitis may lead to rapid and severe loss of vision. Biologics have transformed the management of intraocular inflammation. However, the diagnosis of BD is still a major challenge. In the absence of a reliable biological marker, diagnosis is based on clinical diagnostic criteria and may be delayed after the appearance of the onset sign. However, therapeutic management of BD needs to be introduced early in order to control inflammation, to preserve visual function and to limit irreversible structural damage. -
(PDCO) Minutes of the Meeting on 29 January - 01 February 2019
1 March 2019 EMA/PDCO/56017/2019 Inspections, Human Medicines Pharmacovigilance and Committees Division Paediatric Committee (PDCO) Minutes of the meeting on 29 January - 01 February 2019 Chair: Dirk Mentzer – Vice-Chair: Koenraad Norga 29 January 2019, 14:00- 19:00, room 3A 30 January 2019, 08:30- 19:00, room 3A 31 January 2019, 08:30- 19:00, room 3A 01 February 2019, 08:30- 13:00, room 3A Disclaimers Some of the information contained in this set of minutes is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the PDCO Committee meeting reports (after the PDCO Opinion is adopted), and on the Opinions and decisions on paediatric investigation plans webpage (after the EMA Decision is issued). Of note, this set of minutes is a working document primarily designed for PDCO members and the work the Committee undertakes. Further information with relevant explanatory notes can be found at the end of this document. Note on access to documents Some documents mentioned in the minutes cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on-going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). -
WO 2015/063180 Al 7 May 2015 (07.05.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/063180 Al 7 May 2015 (07.05.2015) P O P C T (51) International Patent Classification: (74) Agent: WILLIAMS, Rachel; Novozymes Biopharma UK A61K 39/00 (2006.01) C07K 16/00 (2006.01) Ltd., Castle Court, 59 Castle Boulevard, Nottingham Not A61K 39/395 (2006.01) tinghamshire NG7 1FD (GB). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP2014/073261 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 29 October 2014 (29.10.2014) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 13 190750.3 29 October 2013 (29. 10.2013) EP SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 14166865.7 2 May 2014 (02.05.2014) EP TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: NOVOZYMES BIOPHARMA DK A S (84) Designated States (unless otherwise indicated, for every [DK/DK]; Krogshoejvej 36, DK-2880 Bagsvaerd (DK). -
Limp Bizkit Behind Blue Eyes Mp3, Flac, Wma
Limp Bizkit Behind Blue Eyes mp3, flac, wma DOWNLOAD LINKS (Clickable) Genre: Rock Album: Behind Blue Eyes Country: US Released: 2003 Style: Pop Rock MP3 version RAR size: 1151 mb FLAC version RAR size: 1732 mb WMA version RAR size: 1280 mb Rating: 4.2 Votes: 880 Other Formats: AUD AAC WMA MMF ASF MPC MIDI Tracklist Hide Credits Behind Blue Eyes (Album Version) 1 4:30 Written By – Pete Townshend Companies, etc. Phonographic Copyright (p) – Flip/Interscope Records Copyright (c) – Flip/Interscope Records Credits Edited By – Dave Holdridge* Engineer – Dave Holdridge*, Elvis Baskette Mixed By – Brendan O'Brien Producer – Fred Durst Notes FOR PROMOTINAL USE ONLY - NOT FOR SALE Barcode and Other Identifiers Matrix / Runout: DISCTRONICS LIMPCDP2 01 Mastering SID Code: IFPI L136 Mould SID Code: IFPI 04AD Other versions Category Artist Title (Format) Label Category Country Year Behind Blue Eyes Interscope 0602498147450 Limpbizkit* 0602498147450 Europe 2003 (CD, Maxi, Enh) Records Behind Blue Eyes Motor / Urban / none Limp Bizkit (CD, Single, Promo, none Germany 2003 Def Jam Group Car) Behind Blue Eyes Interscope 06024 9814743 Limp Bizkit 06024 9814743 Europe 2003 (7") Records Behind Blue Eyes Interscope 0602498147467 Limp Bizkit 0602498147467 Europe 2003 (CD, Single, Car) Records Behind Blue Eyes 06024 9861883 Limp Bizkit (CD, Mini, Single, Motor Music 06024 9861883 Germany 2003 Copy Prot.) Related Music albums to Behind Blue Eyes by Limp Bizkit Limp Bizkit - Rollin' Limp Bizkit - Limp Bizkit - New Old Songs Limp Bizkit - My Generation Limp Bizkit / Dr. Dre & Eminem - N2 Gether Now Limp Bizkit - Gold Cobra Limp Bizkit - If Only We Could Fly Limp Bizkit - Significant Other Limp Bizkit - Results May Vary Limp Bizkit - Chocolate Starfish And The Hot Dog Flavored Water Limp Bizkit - Re-Arranged Limp Bizkit - Three Dollar Bill, Yall$. -
A1068-CD86 Polyclonal Antibody
BioVision 05/16 For research use only CD86 Polyclonal Antibody CATALOG NO: A1068-100 ALTERNATIVE NAMES: T-lymphocyte activation antigen CD86, Activation B7-2 antigen, B70, BU63, CTLA-4 counter-receptor B72, FUN-1, CD86, CD86, CD28LG2 Western blot analysis of CD86 in NCI-H292 cell line lysate AMOUNT: 100 µl IMMUNOGEN: KLH conjugated synthetic peptide between 269-298 amino acids from the C-terminal region of human CD86. MOLECULAR WEIGHT: 37 kDa HOST/ISOTYPE: Rabbit IgG SPECIES REACTIVITY: Human PURIFICATION: This antibody is purified through a protein A column, followed by peptide affinity purification. FORM: Liquid FORMULATION: Supplied in PBS with 0.09% (W/V) sodium azide. STORAGE CONDITIONS: Maintain refrigerated at 2-8°C for up to 6 months. For long term RELATED PRODUCTS storage store at -20°C in small aliquots to prevent freeze-thaw cycles. DESCRIPTION: This gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. This protein is expressed by Human CellExp™ B7-2 /CD86, human recombinant (Cat. No. 7496-10, -50) antigen-presenting cells, and it is the ligand for two proteins at the CD86 (Human) ELISA Kit (Cat. No. K4175-100) cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte- Human CellExp™LAG3 /CD223, human recombinant (Cat. No. 7278-10, -50) associated protein 4. Binding of this protein with CD28 antigen is a costimulatory signal for activation of the T-cell. Binding of this CD223 (LAG3) Polyclonal Antibody (Cat. No. A1067-100) protein with cytotoxic T-lymphocyte-associated protein 4 negatively regulates T-cell activation and diminishes the immune response. -
Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies
Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models. -
DRUGS REQUIRING PRIOR AUTHORIZATION in the MEDICAL BENEFIT Page 1
Effective Date: 08/01/2021 DRUGS REQUIRING PRIOR AUTHORIZATION IN THE MEDICAL BENEFIT Page 1 Therapeutic Category Drug Class Trade Name Generic Name HCPCS Procedure Code HCPCS Procedure Code Description Anti-infectives Antiretrovirals, HIV CABENUVA cabotegravir-rilpivirine C9077 Injection, cabotegravir and rilpivirine, 2mg/3mg Antithrombotic Agents von Willebrand Factor-Directed Antibody CABLIVI caplacizumab-yhdp C9047 Injection, caplacizumab-yhdp, 1 mg Cardiology Antilipemic EVKEEZA evinacumab-dgnb C9079 Injection, evinacumab-dgnb, 5 mg Cardiology Hemostatic Agent BERINERT c1 esterase J0597 Injection, C1 esterase inhibitor (human), Berinert, 10 units Cardiology Hemostatic Agent CINRYZE c1 esterase J0598 Injection, C1 esterase inhibitor (human), Cinryze, 10 units Cardiology Hemostatic Agent FIRAZYR icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent HAEGARDA c1 esterase J0599 Injection, C1 esterase inhibitor (human), (Haegarda), 10 units Cardiology Hemostatic Agent ICATIBANT (generic) icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent KALBITOR ecallantide J1290 Injection, ecallantide, 1 mg Cardiology Hemostatic Agent RUCONEST c1 esterase J0596 Injection, C1 esterase inhibitor (recombinant), Ruconest, 10 units Injection, lanadelumab-flyo, 1 mg (code may be used for Medicare when drug administered under Cardiology Hemostatic Agent TAKHZYRO lanadelumab-flyo J0593 direct supervision of a physician, not for use when drug is self-administered) Cardiology Pulmonary Arterial Hypertension EPOPROSTENOL (generic) -
Specialty Pipeline Monthly Update
Specialty Pipeline Monthly Update Critical updates in an ever changing environment July 2018 New approvals ● Braftovi™ (encorafenib) + Mektovi® (binimetinib): Array BioPharma received U.S. Food and Drug Administration (FDA) approval for Braftovi and Mektovi, to be used in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. The FDA also granted approval of the THxID BRAF Kit (bioMereieux) as a companion diagnostic for these therapeutics. The recommended doses are Mektovi 45 mg orally twice daily and Braftovi 450 mg orally once daily. ● Tibsovo (ivosidenib): Agios Pharmaceuticals received FDA approval for the treatment of relapsed or refractory acute myeloid leukemia (r/r/AML) with susceptible IDH1 mutation. Tibsovo is taken orally once daily until disease progression or unacceptable toxicity. It is estimated that 6 – 10% of AML patients have the IDH1 mutation. ● Nivestym™ (filgrastim-aafi): The FDA approved Pfizer’s Nivestym, a filgrastim biosimilar to Amgen’s Neupogen®, for the same indications as Neupogen, except for the treatment of patients acutely exposed to myelosuppressive doses of radiation (hematopoetic syndrome of acute radiation syndrome). Nivestym follows Sandoz’s biosimilar to Neupogen, Zarxio®, which has been available since 2015. New indications ● Cinryze® (C1 esterase inhibitor [human]): The FDA expanded the indication for Shire’s Cinryze to include pediatric patients with hereditary angioedema (HAE) to use for routine prophylaxis against HAE attacks in children 6 years of age and older. ● Keytruda (pembrolizumab): Merck received FDA approval for Keytruda for the treatment of adult and pediatric patients with refractory primary mediastinal B-cell lymphoma (PMBCL) who relapsed after, were refractory to, or were ineligible for bone marrow transplant and failed two or more prior lines of therapy. -
Novartis R&D and Investor Update
Novartis AG Investor Relations Novartis R&D and investor update November 5, 2018 Disclaimer This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as “potential,” “expected,” “will,” “planned,” “pipeline,” “outlook,” “agreement to acquire,” or similar expressions, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this presentation, or regarding potential future revenues from such products, or regarding the proposed acquisition of Endocyte, Inc. (Endocyte) by Novartis including the potential outcome and expected timing for completion of the proposed acquisition, and the potential impact on Novartis of the proposed acquisition, including express or implied discussions regarding potential future sales or earnings of Novartis, and any potential strategic benefits, synergies or opportunities expected as a result of the proposed acquisition. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this presentation will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. -
Review Anti-Cytokine Biologic Treatment Beyond Anti-TNF in Behçet's Disease
Review Anti-cytokine biologic treatment beyond anti-TNF in Behçet’s disease A. Arida, P.P. Sfikakis First Department of Propedeutic Internal ABSTRACT and thrombotic complications (1-3). Medicine Laikon Hospital, Athens, Unmet therapeutic needs in Behçet’s Treatment varies according to type and University Medical School, Greece. disease have drawn recent attention to severity of disease manifestations. Cor- Aikaterini Arida, MD biological agents targeting cytokines ticosteroids, interferon-alpha and con- Petros P. Sfikakis, MD other than TNF. The anti-IL-17 anti- ventional immunosuppressive drugs, Please address correspondence to: body secukinumab and the anti-IL-2 such as azathioprine, cyclosporine-A, Petros P. Sfikakis, MD, receptor antibody daclizumab were not cyclophosphamide and methotrexate, First Department of Propedeutic superior to placebo for ocular Behçet’s and Internal Medicine, are used either alone or in combination Laikon Hospital, in randomised controlled trials, com- for vital organ involvement. During the Athens University Medical School, prising 118 and 17 patients, respec- last decade there has been increased use Ag Thoma, 17, tively. The anti-IL-1 agents anakinra of anti-TNF monoclonal antibodies in GR-11527 Athens, Greece. and canakinumab and the anti-IL-6 patients with BD who were refractory E-mail: [email protected] agent tocilizumab were given to iso- to conventional treatment or developed Received on June 7, 2014; accepted in lated refractory disease patients, who life-threatening complications (4, 5). revised form on September 17, 2014. were either anti-TNF naïve (n=9) or Anti-TNF treatment has been shown to Clin Exp Rheumatol 2014; 32 (Suppl. 84): experienced (n=18). -
BLA 761125 Page 7
BLA 761125 Page 7 HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------WARNINGS AND PRECAUTIONS---------------------- These highlights do not include all the information needed to use BEOVU Endophthalmitis and retinal detachments may occur following intravitreal safely and effectively. See full prescribing information for BEOVU. injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay (5.1). BEOVU® (brolucizumab-dbll) injection, for intravitreal injection Increases in intraocular pressure (IOP) have been seen within 30 minutes of Initial U.S. Approval: 2019 an intravitreal injection (5.2). ----------------------------INDICATIONS AND USAGE------------------------- There is a potential risk of arterial thromboembolic events (ATE) following BEOVU is a human vascular endothelial growth factor (VEGF) inhibitor intravitreal use of VEGF inhibitors (5.3). indicated for the treatment of Neovascular (Wet) Age-Related Macular ------------------------------ADVERSE REACTIONS----------------------------- Degeneration (AMD) (1). The most common adverse reactions (≥ 5%) reported in patients receiving ----------------------DOSAGE AND ADMINISTRATION---------------------- BEOVU are vision blurred (10%), cataract (7%), conjunctival hemorrhage BEOVU is administered by intravitreal injection. The recommended dose for (6%), eye pain (5%), and vitreous floaters (5%) (6.1). BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) monthly (approximately To report SUSPECTED ADVERSE REACTIONS, contact Novartis every 25-31 days) for the first three doses, followed by one dose of 6 mg (0.05 Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA mL) every 8-12 weeks (2). 1088 or www.fda.gov/medwatch. ---------------------DOSAGE FORMS AND STRENGTHS-------------------- See 17 for PATIENT COUNSELING INFORMATION. Injection: 6 mg/0.05 mL solution for intravitreal injection in a single-dose vial (3).