WO1984003105A1 - Anticorps monoclonal - Google Patents

Anticorps monoclonal Download PDF

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Publication number
WO1984003105A1
WO1984003105A1 PCT/GB1984/000031 GB8400031W WO8403105A1 WO 1984003105 A1 WO1984003105 A1 WO 1984003105A1 GB 8400031 W GB8400031 W GB 8400031W WO 8403105 A1 WO8403105 A1 WO 8403105A1
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WO
WIPO (PCT)
Prior art keywords
antibody
human interferon
monoclonal antibody
interferon
ifn
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Application number
PCT/GB1984/000031
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English (en)
Inventor
David Stanley Secher
Original Assignee
David Stanley Secher
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by David Stanley Secher filed Critical David Stanley Secher
Priority to GB08423719A priority Critical patent/GB2146351B/en
Publication of WO1984003105A1 publication Critical patent/WO1984003105A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/249—Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • This invention relates to a monoclonal antibody.
  • the invention relates to a monoclonal antibody to human interferon - ⁇ , a process for the preparation of the monoclonal antibody, the use of the monoclonal antibody in an immunoassay for human interferon - ⁇ , the use of the monoclonal antibody in a process for the immunopurification of a sample containing human interferon - ⁇ and an assay for antibody to human interferon - ⁇ .
  • Interferon is the generic name for a group of proteins which exhibit such properties as antiviral activity and cell growth inhibition (Stewart W.E. (1979). "The interferon system”. Springer, Vienna and “The Biology of the interferon system.” Elsevier-North Holland Biochemical Press, Amsterdam).
  • the interferons may be divided into three main types; interferon- ⁇ (IFN - ⁇ or leukocyte interferon), interferon- ⁇ (IFN- ⁇ or fibroblast interferon) and interferon - ⁇ (IFN- ⁇ or immune-interferon) (Stewart W.E. et al (1980) "Interferon Nomenclature", Nature, London 286.
  • the present invention relates to a monoclonal antibody to interferon- ⁇ and in particular to human interferon- ⁇ (Hu-IFN- ⁇ ).
  • Hu-IFN- ⁇ comprises a number of distinct molecular entities, known as sub-types. There are eight to twelve identified sub-types of Hu-IFN- ⁇ the relative proportions of which are yet to be established. The sub types are each about 165 amino acid residues in length and have many homologous features. It is thought that in all there may be up to 20 different sub-types of natural Hu-IFN- ⁇ since 20 different genes for Hu-IFN- ⁇ have to date been recognised. For historical reasons, the nomenclature of the Hu-IFN- ⁇ sub-types is not standard, one method relying upon an alphabetical system and an alternative method relying on a numerical system. The relationship between them is as follows :
  • a monoclonal antibody to human interferon- ⁇ wherein the monoclonal antibody has a greater binding efficiency to D sub-type human interferon- ⁇ than to A sub-type human interferon- ⁇ .
  • the monoclonal antibody has a greater binding efficiency to D sub-type human interferon- than to any of the other sub-types of human interferon- ⁇ .
  • the monoclonal antibody is produced by the cell line designated YOK5/19.
  • binding efficiency is a measure of the relative affinity of a monoclonal antibody for a particular sub-type of human interferon- ⁇ . The binding efficiency not only reflects the specificity of a monoclonal antibody but also the avidity of the immunochemical bond formed between the monoclonal antibody and its corresponding antigenic determinant.
  • the terra "complementary binding efficiency" as used herein, refers to a binding efficiency which complements that of the monoclonal antibody according to the first aspect of the invention.
  • An example of an antibody having a complementary binding efficiency is a monoclonal antibody derived from the NK2 cell line.
  • NK2 cell line and its preparation are described in detail in published British patent application GB 2083836A (see also international published application WO 80/02899).
  • the binding efficiency of a monoclonal antibody to a human interferon- ⁇ sub-type is preferably measured by immobilising a sample of the sub-type on a solid support (for example by way of an immobilised monoclonal antibody to human interferon- ⁇ ).
  • a radioactively labelled monoclonal antibody under test is then incubated with the immobilised pure sub-type and after rinsing, the specific radioactivity of the solid support is measured.
  • the bound radioactivity is a measure of the binding efficiency of the monoclonal antibody to the sub-type.
  • a neutralization test may be employed in which for example the binding efficiency is assessed by the measurement of the inhibition of viral RNA synthesis which results from unn ⁇ utralized interferon remaining in a test sample following admixture of a sample of the sub-type of human interfero ⁇ n- ⁇ and the monoclonal antibody.
  • a composition comprising, in combi on, a monoclonal antibody according to the first aspect of the present invention and a monoclonal antibody of complementary binding efficiency.
  • the monoclonal antibody of complementary binding efficiency is derived from the NK2 cell line.
  • the advantage of such a composition is that the two monoclonal antibodies of complementary binding efficiency have in combination a high binding efficiency for most human interferon- ⁇ sub-types.
  • a third aspect of the present invention we provide a process for the immunopurification of a sample containing human interferon- ⁇ in which either a monoclonal antibody according to the first aspect of the present invention or a composition according to the second aspect of the present invention is immobilised upon a solid support form an immunopurification medium and the sample containing human interferon- ⁇ is contacted with the medium.
  • the antibody may for example be immobilised upon a particulate solid support.
  • Each particle of the support may have attached a monoclonal antibody of the first aspect of the invention, an antibody of complementary binding efficiency or both.
  • a mixture of particles may be used to produce an immunopurification column.
  • a fourth aspect of the present invention we provide a process for the immuno purification of a sample containing numan interferon- ⁇ wherein the sample is passed sequentially, in either order, through an immunopurification column comprising, immobilised, a monoclonal antibody according. to the first aspect of the present invention and an immunopurification column comprising, immobilised, a monoclonal antibody of complementary binding efficiency.
  • the monoclonal antibody of complementary binding efficiency is dereived from the NK2 cell line.
  • the columns may be separate or may be integral.
  • a fifth as.pect of the present invention we provide an immunoassay for human interferon- ⁇ comprising the use of an antibody according to the first aspect of the present invention.
  • the assay uses a sample to be assayed for human interferon- ⁇ , a first antibody to human interferon- ⁇ , the first antibody being bound to a solid phase support and a second antibody to human interferon- ⁇ , the second antibody having a label attached thereto, wherein one of the first and second antibodies is a monoclonal antibody according to the first aspect of the present invention and the other antibody is either a polyclonal antibody to human inteferon- ⁇ or a monoclonal antibody of complementary binding efficiency the assay comprising the steps of placing the sample, the first antibody and the second antibody in contact, in any order or combination, and measuring the amount of second antibody bound to the solid phase through human interferon- ⁇ and the first antibody.
  • the sample is placed in contact with the first antibody in one step, followed by the addition of second antibody.
  • the first antibody is a polyclonal antibody (for example sheep anti interferon- ⁇ ) and the second antibody is a monoclonal antibody according to the first aspect of the present invention.
  • the label is a radioactive label but may be for example an enzyme, a chromophore, a fluorophore, a chemiluminescent chemical group or any other moiety capable of producing a detectable signal.
  • the polyclonal antibody to human interferon- ⁇ is sheep anti-interferon- ⁇ .
  • the monoclonal antibody of complementary binding efficiency is derived from the NK2 cell line.
  • an immunoassay for a first antibody to human interferon- ⁇ in which is used a sample to be assayed for the first antibody to human interferon- ⁇ a solid phase support having bound thereto a second antibody to human interferon- ⁇ , the second antibody being bound to human interferon- ⁇ a third antibody, the third antibody having a label attached thereto and being capable of binding to the first antibody, the assay comprising the steps of placing the solid phase support in contact with the sample, thereby allowing first antibody to bind to the human interferon- ⁇ attached to the solid phase through the second antibody, placing the solid phase support in contact with the third antibody thereby allowing the third antibody to bind to any first antibody which is attached to the solid phase through the human interfei-on- ⁇ and the second antibody, and measuring the amount of third antibody associated with the solid phase.
  • the second antibody is sheep anti-interferon and the third antibody is radioactively labelled sheep antibody to the first antibody.
  • the second antibody may be an antibody having a complementary binding efficiency and is preferably a monoclonal antibody to human interferon- ⁇ derived from the NK2 cell line.
  • a seventh aspect of the present invention we provide a process for the production of a hybridoma cell line capable of secreting a monoclonal antibody according to the first aspect of the present invention comprising the steps of immunizing an animal with human interferon- ⁇ , allowing the immune system of the animal to generate lymphocytes to human interferon- ⁇ , preparing a sample of spleen cells taken from the animal fusing the spleen cells with myeloma cells to form a colony of hybridoma cells, and screening the colony of hybridoma cells for cells secreting monoclonal antibody according to the first aspect of the invention wherein the screening step employs an assay according to the sixth aspect of the invention, the third antibody having been passed through an immunopurification column, comprising immobilised antibody of a complementary binding efficiency, prior to use in the assay.
  • the antibody of complementary binding efficiency is a monoclonal antibody derived from the NK2 cell line.
  • the third antibody is radioactively labelled sheep antibody to the first antibody.
  • the second antibody is a monoclonal antibody derived from the NK2 cell line.
  • Figure 3 is a bar chart showing the results of anti-interferon binding assay on a panel of interferons using YOK5/19
  • Figure 4 is a bar chart showing the results of an IRMA assay conducted on a panel of interferons using a monoclonal and a polyclonal antibody.
  • the monoclonal antibody was prepared by immunising a rat with human interferon- ⁇ , fusing rat spleen cells with myeloma cells, and selecting clones secreting the desired type of antibody.
  • the antigen used in the immunisation was human interferon- ⁇ prepared from leucocytes (Hu-IFN- ⁇ (Le)) ("P-IF") (Cantell et al., 1981) and was obtained from Dr. K. Cantell, Helsinki (Batch 191207 8-A, 38 x 106 U/ml, 28 mg/ml total protein).
  • the antigen was diluted in phosphate buffered saline
  • the rat was bled from the tail and serum samples collected at approximately weekly intervals and the sera tested for their ability to neutralise the antiviral activity of IFN- ⁇ in a plaque reduction assay.
  • 10U of IFN when incubated on a monolayer of normal human cells before the addition of a titred dose of vesicular stomatitis virus, resulted in a reduction in the number of viral plaques to about 20% of the number of plaques in the control (no IFN).
  • Preincubation of the interferon with a sample of the rate serum (at a final dilution of 1/60) before adding to the cell monolayer gave in some cases restoration of the number of piaques (see Table 2).
  • +++ 80% of restoration of plaque number.
  • the culture supernatants were tested in a assay designed to detect anti-interferon antibodies. This assay is a modification of that designed to measure interferon concentrations by immunoradiometric assay (Secher, 1981). sheep anti-interferon antibodies are coated onto a plastic substratum. This may be in the form of tubes or beads or the wells of microtiter trays. We preferred the use of 96-well microtiter trays.
  • a solution containing Hu-IFN- ⁇ (100 ⁇ l, about 4000 V/ml in Blocking Medium) is added to each well except for control wells, to which 100 ⁇ l Blocking Medium is added. After a 2 hour incubation at 20-25°, the interferon is removed and 100 ⁇ l of the solution to be tested is added to the well.
  • test solution is removed and the wells washed twice with PBS, 0.5% BSA, 0.1% NaN 3 . Care should be taken to remove all the test solution and to perform the washes as quickly as possible.
  • the next step involves incubation with labelled anti-rat Ig antibody.
  • 100 ⁇ l of 125 I-labelled sheep anti-rat immunoglobulin antibody, (5 x 10 5 - 10 6 cpm/ml, 1 ⁇ Ci/ ⁇ g , affinity purified sheep antibody in PBS, 0.5% BSA, 0.1% NaN 3 ) is added to each well and incubated for about 2 hours at 20-25°.
  • the unbound labelled antibody is then removed and the wells washed twice more with PBS, 0.5% BSA, 0.1% NaN 3 .
  • the radioactivity remaining in each well is a measure of the bound sheep anti-rat Ig, which in turn is a measure of the rat anti-interferon antibody that bound to the solid-phase via the interferon-sheep anti-interferon bridge. This radioactivity may be measured by cutting off the bottom of the wells with a hot wire and transferring each well to a tube for counting in a gamma counter.
  • An alternative form of this assay uses monoclonal antibody (e.g. NK2) attached to the plastic instead of sheep anti-interferon.
  • NK2 monoclonal antibody
  • the labelled sheep anti-rat Ig antibody should be passed through an NK2-Sepharose column before use to remove any antibodies that bind to NK2.
  • This form of the assay has the advantage that only antibodies recognising a distinct antigenic determinant from that recognized by NK2 will give a positive signal, but antibodies that bind only to IFN species that lack the NK2 determinant will not lead to a positive signal.
  • the cells continued to grow well and produce anti-interferon antibody. These cells. (YOK5/19 (3) (As)) were again subjected to dilution fractionation as above and a culture, YOK5/19 (3) (As) (3.80) selected on the basis of a binding assay (Table 4) using sheep anti-interferon and either crude Hu-IFN- ⁇ (Le) or a cloned IFn ⁇ 1 Cells from this culture were then successfully cloned on semi-solid support as described (Galfre & Milstein, 1981) except that agarose was used instead of agar and mouse peritoneal cells were attached to the petri dishes before addition of the agarose.
  • Clones were picked from a petri dish containing about 20 clones, and 10 out of 13 tested were positive in the anti-interferon assay.
  • the column was then eluted with 420 ml of 10 mM sodium phosphate buffer, pH7.4, followed by a linear gradient of 10-100 mM sodium phosphate, pH7.4 (800 r ⁇ ls + 800 mis). Fractions were collected (12.3 mis) and the absorbance (280nm) of the column eluate continuously monitored. The fractions comprising the first peak to elute after the beginning of the gradient were identified as pure YOK/19 antibody by cellulose acetate electrophoresis, pooled, dialysed against distilled water and lyophilised. The yield of protein in one such experiment was 313 mg.
  • Radiolabelling of YOK5/19 antibody YOK/19 antibody purified as above was radiolabelled with 125 I using chloramine-T as previously described for NK2 (Secher, 1981). A specific activity of about 20 ⁇ Ci/ ⁇ g (3Ci/ ⁇ mole) was obtained.
  • YOK5/19 can neutralise the antiviral activity of and of the major components of Naraalwa IFN.
  • the panel of IFNs consisted of crude leucocyte IFN(Hu-IFN- ⁇ (Le), the effluent when crude leucocyte IFN was passed through an NK2-Sepharose column and thus depleted of NK2 recognised interferons ("NK2 effluent"), a cloned Hu-IFN- ⁇ (D sub-type) and cloned Hu-IFNs ⁇ -A, -B, -C, -D, -F, -I, J, K.
  • the cpm bound when no IFN was added to the assay defined the non-specific binding (usually 200-400 cpm) that was subtracted from the other values.
  • Tables 5 and 6 show the results of different such experiments, and indicate the reproducibility of the assay. The results clearly show that whereas NK2 recognises A,B,C,D but not F, YOK5/19 is most active with IFN-D.
  • YOK5/19 (1) is a subculture of the original YOK5/19.
  • YOK4.1.C6 is a culture from a different fusion that was los.t.
  • the anti-interferon binding assay described above was also used to measure the relative concentration of YOK5/19 antibody in different samplers. For each sample a series of dilutions was prepared and the cpm bound in the assay using a suitable IFN (e.g. IFN- ⁇ 1 or crude IFN) measured for each dilution. The results of such an experiment are shown in Figs. 1, from which it can be seen that the titre (dilution at which half maximal cpm bound) is between 1/104 and 1/105, about 100 fold more concentrated than in the supernatant of YOK5/19 cells before cloning. A control experiment was performed with no interferon- ⁇ present to obtain a background cpm bound value.
  • IFN e.g. IFN- ⁇ 1 or crude IFN
  • Immunoglobulin class of YOK5/19.31.9 antibody YCK5/19.31.9 cells were grown in 14C-lysine containing medium and the radioactive supernatant subjected to SDS-polyacrylamide gel electrophoresis and autoradiography as described (Galfre & Milstein, 1981). The autoradiography clearly showed the existance of a single ( ⁇ ) heavy chain and a single light chain, supporting the monoclonal nature of YOK5/19.31.9 and establishing the antibody as an IgG. A similar conclusion was reached from SDS-polyacrylamide gel electrophoresis of
  • 125 I-YOK5/19 purified antibody labelled as described above. The only bands visible in the autoradiograph had the mobility of heavy ( ⁇ ) and light chains.
  • Immunoradiometric assays with YOK5/19 Various analogues of the immunoradiometric assay (IRMA) previously described for measuring IFN- ⁇ (Secher, 1981) were constructed and tested. These involved the use of 124 l-labelled YOK5/19 antibody prepared as described above or plastic beads (or other solid support) coated with YOK5/19 antibody.
  • Table 7 lists those combinations of monoclonal antibodies that were tested as possible IRMAs for Hu-IFN- ⁇ .
  • a "reverse IRMA” using sheep anti IFN- ⁇ in solution has been described (Hawkins & Secher, 1983).
  • the assay involved solid phase NK2 antibody and radiolabelled YOK5/19 antibody.
  • the assay involved solid phase YOK5/19 antibody and radiolabelled NK2 antibody IFN- ⁇ -B, -F, and ⁇ 1 all seem to be unrecognised in the combined assay.
  • the other species tested are all recognised in at least one of the assays.
  • the different relative sentitivities are probably due to differences in the avidity of the two monoclonal antibodies to the various species and the fact that the solid phase antibody is at an effective concentration far higher than that of the radiolabelled antibody.
  • IgG purified from serum and ascites fluid of rats carrying YOK5/19 tumours and coupled to
  • Sepharose 4B as described above has been used in the immunopurification of Hu-IFN- ⁇ from leukocytes and from E. coli producing Hu-IFN- ⁇ 1.
  • YOK5/19 antibody the antibody produced by cells of clone YOK5/19.31.9 (originally called YOK5/19(3)(Ag)(3.80).31.9) or of the similar clones YOK5/19.31, YOK5/19.22, YOK5/19.8, is referred to as YOK5/19 antibody.
  • the abbreviation to YOK5 is analogous to the NK2 abbreviation for NK2/13.35.6 (Secher & Burke, 1980).
  • Interferon purified on YOK5-Sepharose is referred to as "YOK5-IFN", also following an accepted convention for NK2. References Atherton, K.T.A. and Burke, D.S.

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Abstract

Anticorps monoclonal possédant une plus grande efficacité de liaison avec l'interféron alpha humain du sous-type D qu'avec l'interféron alpha humain du sous-type A. Un anticorps monoclonal particulier est appelé YOK5/19. Procédé de préparation de l'anticorps monoclonal et utilisations de l'anticorps monoclonal en immunopurification et en analyse immunologique.
PCT/GB1984/000031 1983-02-04 1984-02-06 Anticorps monoclonal WO1984003105A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB08423719A GB2146351B (en) 1983-02-04 1984-02-06 Monoclonal antibody

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GB838303165A GB8303165D0 (en) 1983-02-04 1983-02-04 Monoclonal antibody

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WO1984003105A1 true WO1984003105A1 (fr) 1984-08-16

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PCT/GB1984/000031 WO1984003105A1 (fr) 1983-02-04 1984-02-06 Anticorps monoclonal

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0119476A2 (fr) * 1983-02-22 1984-09-26 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Lignées de cellules hybrides produisant de l'immunoglobuline, leur application et procédé de préparation
EP0158420B1 (fr) * 1984-02-24 1990-11-07 Schering Corporation Anticorps monoclonaux à l'égard de l'interféron alpha-2 et hybridomes produisant de tels anticorps
WO1995024212A1 (fr) * 1994-03-07 1995-09-14 Imperial College Of Science, Technology & Medicine Utilisation de sous-types d'interferons dans la preparation de medicaments permettant de traiter des infections virales
US7087726B2 (en) 2001-02-22 2006-08-08 Genentech, Inc. Anti-interferon-α antibodies
WO2008137838A2 (fr) 2007-05-03 2008-11-13 Medimmune, Llc Marqueurs pharmacodynamiques alpha-induit d'interféron
WO2009061818A1 (fr) 2007-11-05 2009-05-14 Medimmune, Llc Procédés de traitement de la sclérodermie
WO2009100342A2 (fr) 2008-02-08 2009-08-13 Medimmune, Llc Marqueurs de troubles et leur utilisation
WO2011028933A1 (fr) 2009-09-03 2011-03-10 Medimmune, Llc Diagnostic d'interféron de type 1
EP2712930A2 (fr) 2006-12-06 2014-04-02 MedImmune, LLC Marqueurs pharmacodynamiques par induction alpha d'interféron
WO2020165437A1 (fr) 2019-02-15 2020-08-20 Astrazeneca Ab Troubles induits par l'interféron de type i

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981002899A1 (fr) * 1980-04-11 1981-10-15 D Secher Anticorps monoclonal
WO1982001773A1 (fr) * 1980-11-07 1982-05-27 Secher David S Analyse pour l'interferon
FR2500754A1 (fr) * 1981-02-27 1982-09-03 Hoffmann La Roche Anticorps monoclonaux

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981002899A1 (fr) * 1980-04-11 1981-10-15 D Secher Anticorps monoclonal
WO1982001773A1 (fr) * 1980-11-07 1982-05-27 Secher David S Analyse pour l'interferon
FR2500754A1 (fr) * 1981-02-27 1982-09-03 Hoffmann La Roche Anticorps monoclonaux

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Nature, Vol. 294, No. 5838, 19 November 1981 (Chesham, Bucks, GB) H. ARNHEITER et al.: "Physicochemical and Antigenic Properties of Synthetic Fragments of Human Leykocyte Interferon", pages 278-280, see page 279, Table 1 and page 280, right-hand column, lines 9-15 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0119476A2 (fr) * 1983-02-22 1984-09-26 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Lignées de cellules hybrides produisant de l'immunoglobuline, leur application et procédé de préparation
EP0119476A3 (fr) * 1983-02-22 1987-04-08 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Lignées de cellules hybrides produisant de l'immunoglobuline, leur application et procédé de préparation
EP0158420B1 (fr) * 1984-02-24 1990-11-07 Schering Corporation Anticorps monoclonaux à l'égard de l'interféron alpha-2 et hybridomes produisant de tels anticorps
WO1995024212A1 (fr) * 1994-03-07 1995-09-14 Imperial College Of Science, Technology & Medicine Utilisation de sous-types d'interferons dans la preparation de medicaments permettant de traiter des infections virales
US6007805A (en) * 1994-03-07 1999-12-28 Imperial College Of Science And Technology Use of interferon subtype alpha-8 (IFN-α8) to treat viral infections of the liver
US7582445B2 (en) 2001-02-22 2009-09-01 Genentech, Inc. Anti-interferon-α antibodies
US7087726B2 (en) 2001-02-22 2006-08-08 Genentech, Inc. Anti-interferon-α antibodies
US7910707B2 (en) 2001-02-22 2011-03-22 Genentech, Inc. Anti-interferon-α antibodies
US8349331B2 (en) 2001-02-22 2013-01-08 Genentech, Inc. Anti-interferon-α antibodies
EP2712930A2 (fr) 2006-12-06 2014-04-02 MedImmune, LLC Marqueurs pharmacodynamiques par induction alpha d'interféron
WO2008137838A2 (fr) 2007-05-03 2008-11-13 Medimmune, Llc Marqueurs pharmacodynamiques alpha-induit d'interféron
WO2009061818A1 (fr) 2007-11-05 2009-05-14 Medimmune, Llc Procédés de traitement de la sclérodermie
WO2009100342A2 (fr) 2008-02-08 2009-08-13 Medimmune, Llc Marqueurs de troubles et leur utilisation
WO2011028933A1 (fr) 2009-09-03 2011-03-10 Medimmune, Llc Diagnostic d'interféron de type 1
WO2020165437A1 (fr) 2019-02-15 2020-08-20 Astrazeneca Ab Troubles induits par l'interféron de type i

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JPS60500714A (ja) 1985-05-16
GB8303165D0 (en) 1983-03-09
GB2146351B (en) 1986-10-22
GB8423719D0 (en) 1984-10-24
GB2146351A (en) 1985-04-17
EP0134803A1 (fr) 1985-03-27

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