DE19953696A1 - Selective non-peptidic proteolytic enzyme analogue useful for the dissolution of plaques and treatment of polypeptide mediated illnesses comprises proteolytic amino acid residues bonded to a carrier molecule - Google Patents
Selective non-peptidic proteolytic enzyme analogue useful for the dissolution of plaques and treatment of polypeptide mediated illnesses comprises proteolytic amino acid residues bonded to a carrier moleculeInfo
- Publication number
- DE19953696A1 DE19953696A1 DE19953696A DE19953696A DE19953696A1 DE 19953696 A1 DE19953696 A1 DE 19953696A1 DE 19953696 A DE19953696 A DE 19953696A DE 19953696 A DE19953696 A DE 19953696A DE 19953696 A1 DE19953696 A1 DE 19953696A1
- Authority
- DE
- Germany
- Prior art keywords
- proteolytic
- synzyme
- molecule
- amino acid
- acid residues
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
- 230000002797 proteolythic effect Effects 0.000 title claims abstract description 21
- 108091005804 Peptidases Proteins 0.000 title claims abstract description 9
- 102000035195 Peptidases Human genes 0.000 title claims abstract description 5
- 125000000539 amino acid group Chemical group 0.000 title claims abstract description 5
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 title description 2
- 238000004090 dissolution Methods 0.000 title 1
- 230000001404 mediated effect Effects 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 title 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 5
- 102000029797 Prion Human genes 0.000 claims abstract description 4
- 108091000054 Prion Proteins 0.000 claims abstract description 4
- ICZWAZVKLACMKR-CIUDSAMLSA-N Asp-His-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CN=CN1 ICZWAZVKLACMKR-CIUDSAMLSA-N 0.000 claims abstract description 3
- 108010040003 polyglutamine Proteins 0.000 claims abstract description 3
- 229920000155 polyglutamine Polymers 0.000 claims abstract description 3
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 claims abstract 2
- 108010040443 aspartyl-aspartic acid Proteins 0.000 claims abstract 2
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 230000001717 pathogenic effect Effects 0.000 claims description 4
- XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical compound C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910003472 fullerene Inorganic materials 0.000 claims description 2
- 229940124549 vasodilator Drugs 0.000 claims description 2
- 239000003071 vasodilator agent Substances 0.000 claims description 2
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims 1
- 229910052711 selenium Inorganic materials 0.000 claims 1
- 239000011669 selenium Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 230000001588 bifunctional effect Effects 0.000 abstract description 2
- 235000004554 glutamine Nutrition 0.000 abstract description 2
- 125000000404 glutamine group Chemical class N[C@@H](CCC(N)=O)C(=O)* 0.000 abstract description 2
- 239000004365 Protease Substances 0.000 description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
- 230000027455 binding Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 206010002022 amyloidosis Diseases 0.000 description 2
- 230000002788 anti-peptide Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001197082 Knodus beta Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Die Erfindung betrifft den Bereich Pharmakologie der proteolytischen Substanzen bzw. Molekülen.The invention relates to the field of pharmacology proteolytic substances or molecules.
Es gibt eine Strategie zur Behandlung der Krankheiten, die durch krankheitserregende Proteine verursacht werden. Eine Protease bzw. Protease-Domäne wird mit einem immunogenischen Peptid oder Antipeptid fusioniert, und somit wir die Substratspezifität dieser Protease nur auf bestimmte, durch das Antipeptid, erkennbare Proteine begrenzt.There is a strategy to treat diseases caused by disease-causing Proteins are caused. A protease or protease domain is marked with a immunogenic peptide or antipeptide fused, and thus we Substrate specificity of this protease only to certain, by the antipeptide, recognizable proteins limited.
Der Erfinder Alexander Cherkasky (s. Stern 25.3.1999 5.19) will die Substratspezifität einer Protease gegen Alzheimer-erregende Beta-Amyloide lenken, damit diese und folglich die von ihren (Beta-Amyloiden) gebildete Plaques gespalten werden können. Da die proteolytischen Fusionsproteinen relativ groß sind, ist es fraglich, ob sie die Blut-Hirn-Schranke überwinden oder nicht.The inventor Alexander Cherkasky (see Stern 25.3.1999 5.19) wants this Substrate specificity of a protease against Alzheimer-causing beta amyloids so that they and consequently the plaques formed by their (beta-amyloids) can be split. Since the proteolytic fusion proteins are relatively large, it is questionable whether they cross the blood-brain barrier or not.
Die Aufgabe der Erfindung ist kleine nicht Peptid ähnliche spezifische proteolytische Moleküle zu schaffen, die effektiv krankheitserregende Peptide und folglich Plaques spalten, und Blut-Hirn-Schranke überwinden können.The object of the invention is small non-peptide-like specific proteolytic Molecules create effective peptides that cause disease and consequently plaques cleave, and can cross the blood-brain barrier.
Die Aufgabe der Erfindung wird dadurch gelöst, dass ein proteolytisches Enzymanalog oder Synzym mit einem spezifischen Beta-Amyloid (BA4), Prion (PrP Sc) oder Huntingtin (Polyglutamin-Kette aus ungefähr 40-60 Glutaminen) - oder einem anderen Molekül verbunden wird, damit ein Plaque oder ein krankheitserregendes (Poly)Peptid spezifisch gespalten werden kann. Dieses bifunktionales Molekül kann mit einem anderen Molekül wie z. B. einer Thiolgruppe, Fulleren oder mit einem anderen antixidatieren Molekül einem Nitrit, Nitrat oder einem anderen vasodilatorischen Molekül u. a. Molekülen verbunden werden.The object of the invention is achieved in that a proteolytic Enzyme analog or synzyme with a specific beta amyloid (BA4), prion (PrP Sc) or Huntingtin (polyglutamine chain consisting of approximately 40-60 glutamines) - or another molecule is connected to make a plaque or a disease-causing (poly) peptide can be cleaved specifically. This bifunctional molecule can with another molecule such as. B. a thiol group, Fullerene or with another antioxidant molecule, a nitrite, nitrate or another vasodilator molecule u. a. Molecules are connected.
In der Fig. 1 ist die allgemeine Struktur eines selektiven proteolytischen Synzyms schematisch dargestellt.In FIG. 1, the general structure of a selective proteolytic Synzyms is shown schematically.
In der Fig. 1a ist eine Kombination aus einem proteolytischen Synzym 1 und einem spezifisch - bindenden Molekül 2 schematisch dargestellt.A combination of a proteolytic synzyme 1 and a specifically binding molecule 2 is shown schematically in FIG. 1a.
In der Fig. 1b ist das proteolytische Synzym 1 zwischen der beiden spezifisch - bindenden Molekülen 2 schematisch dargestellt.The proteolytic synzyme 1 between the two specific binding molecules 2 is shown schematically in FIG. 1b.
In der Fig. 1c ist das spezifisch - bindende Molekül 2 zwischen der beiden proteolytischen Synzymen 1 schematisch dargestellt. . Binding molecule 2 shown schematically between the two proteolytic Synzymen 1 - in Figure 1c, the specific.
In der Fig. 2 sind die Formeln einiger proteolytischen Synzyme dargestellt.In FIG. 2, the formulas are shown some proteolytic synzymes.
In der Fig. 2a ist die Formel eines Aspartyl - proteolytischen Synzyms dargestelllt. Das ist ein Enzymanalog von Aspartyl - proteasen. The formula of an aspartyl-proteolytic synzyme is shown in FIG. 2a. This is an enzyme analogue of aspartyl proteases.
In der Fig. 2b ist die Formel eines Serin - proteolytischen Synzyms daregestellt. Das Trizyklin ist das Basis-Molekül, an welchem die Aminosäurereste der katalytischen Asp-His-Ser-Triade von den Serinproteasen gebunden sind. Somit wird das aktive oder katalytische Zentrum von Serinproteasen immitiert.The formula of a serine-proteolytic synzyme is shown in FIG. 2b. The tricycline is the base molecule to which the amino acid residues of the catalytic Asp-His-Ser triad are bound by the serine proteases. The active or catalytic center of serine proteases is thus imitated.
In der Fig. 2c ist die Formel eines Cystein - proteolytischen Synzymes vereinfacht dargestellt.The formula of a cysteine-proteolytic synzyme is shown in simplified form in FIG. 2c.
Das Trizyklin ist auch das Basis-Molekül, an welchem die wichtigsten Cystein - und Histidin Aminosäureresten des Cystein - Proteasen gebunden sind. Ein selektives proteolytisches Synzym, welches in den Fig. 1 und 2 dargestellt ist, erkennt und bindet durch ein spezifisch - bindendes Molekül ein krankheitserregenden bzw. pathogenes (Poly) Peptid. Durch dieses spezifisch - bindendes Molekül wird das pathogene (Poly) Peptid durch das proteolytishes Synzym selektiv bzw. spezifisch gespalten.The tricycline is also the base molecule to which the most important cysteine and histidine amino acid residues of the cysteine proteases are bound. A selective proteolytic synzyme, which is shown in FIGS . 1 and 2, recognizes and binds a disease-causing or pathogenic (poly) peptide by means of a specifically binding molecule. This specific binding molecule cleaves the pathogenic (poly) peptide selectively or specifically by the proteolytic synzyme.
Nach der Spaltung wird das pathogene (Poly) Peptid wie z. B. Beta-Amyloid, Huntingtin, Prion - Protein, u.v.a. Proteine nicht mehr gefährlich, weil die extrazellulären Plaques gespalten und danach abgeführt werden. Die Klasse von selektiven proteolytischen Wirkstoffen wird vom Erfinder als "Proteopharmaka" oder "Proteolytica" bzw. "Proteolytica selectiva" bezeichnet.After cleavage, the pathogenic (poly) peptide such. B. beta amyloid, Huntingtin, prion - protein, etc. Proteins are no longer dangerous because of that extracellular plaques cleaved and then removed. The class of selective proteolytic agents is called "proteopharmaceuticals" by the inventor "Proteolytica" or "Proteolytica selectiva" referred to.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19953696A DE19953696A1 (en) | 1999-11-09 | 1999-11-09 | Selective non-peptidic proteolytic enzyme analogue useful for the dissolution of plaques and treatment of polypeptide mediated illnesses comprises proteolytic amino acid residues bonded to a carrier molecule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19953696A DE19953696A1 (en) | 1999-11-09 | 1999-11-09 | Selective non-peptidic proteolytic enzyme analogue useful for the dissolution of plaques and treatment of polypeptide mediated illnesses comprises proteolytic amino acid residues bonded to a carrier molecule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19953696A1 true DE19953696A1 (en) | 2001-05-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19953696A Ceased DE19953696A1 (en) | 1999-11-09 | 1999-11-09 | Selective non-peptidic proteolytic enzyme analogue useful for the dissolution of plaques and treatment of polypeptide mediated illnesses comprises proteolytic amino acid residues bonded to a carrier molecule |
Country Status (1)
| Country | Link |
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| DE (1) | DE19953696A1 (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060403A3 (en) * | 2003-01-06 | 2004-11-18 | Transfert Plus | Aprotinin and anglos as carriers across the blood-brain barrier |
| WO2007009229A1 (en) * | 2005-07-15 | 2007-01-25 | Angiochem Inc. | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| US7557182B2 (en) | 2005-02-18 | 2009-07-07 | Angiochem Inc. | Molecules for transporting a compound across the blood-brain barrier |
| US8710013B2 (en) | 2008-04-18 | 2014-04-29 | Angiochem Inc. | Pharmaceutical compositions of paclitaxel, paclitaxel analogs or paclitaxel conjugates and related methods of preparation and use |
| US8828925B2 (en) | 2008-10-15 | 2014-09-09 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| US8853353B2 (en) | 2008-12-17 | 2014-10-07 | Angiochem, Inc. | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| US8921314B2 (en) | 2008-10-15 | 2014-12-30 | Angiochem, Inc. | Conjugates of GLP-1 agonists and uses thereof |
| US9161988B2 (en) | 2009-07-02 | 2015-10-20 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| US9173891B2 (en) | 2009-04-20 | 2015-11-03 | Angiochem, Inc. | Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog |
| EP2864349A4 (en) * | 2012-06-20 | 2016-02-24 | Univ California | DYNAMIC BIOMEMETICAL CATALYST OF SYNZYME TYPE, CATALYSIS, AND CATALYTIC SYSTEMS |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| US9914754B2 (en) | 2008-12-05 | 2018-03-13 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| US10980892B2 (en) | 2015-06-15 | 2021-04-20 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19822406A1 (en) * | 1998-05-19 | 1999-11-25 | Alexander Cherkasky | Composition for treating cancer and other diseases caused by pathogenic proteins |
-
1999
- 1999-11-09 DE DE19953696A patent/DE19953696A1/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19822406A1 (en) * | 1998-05-19 | 1999-11-25 | Alexander Cherkasky | Composition for treating cancer and other diseases caused by pathogenic proteins |
Non-Patent Citations (1)
| Title |
|---|
| CHERKASKY,Alexander: Hilfe bei Alzheimer. In: Stern-Archiv, 13.Ausg., 25.3.99, S.19 * |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2260874A1 (en) * | 2003-01-06 | 2010-12-15 | Angiochem Inc. | Aprotinin analogs as carriers across the blood-brain barrier |
| JP2006515363A (en) * | 2003-01-06 | 2006-05-25 | アンジオケム・インコーポレーテッド | Aprotinin and analogs as carriers that cross the blood brain barrier |
| US9221867B2 (en) | 2003-01-06 | 2015-12-29 | Angiochem Inc. | Method for transporting a compound across the blood-brain barrier |
| WO2004060403A3 (en) * | 2003-01-06 | 2004-11-18 | Transfert Plus | Aprotinin and anglos as carriers across the blood-brain barrier |
| US8828949B2 (en) | 2005-02-18 | 2014-09-09 | Angiochem, Inc. | Aprotinin polypeptides for transporting a compound across the blood-brain barrier |
| US7902156B2 (en) | 2005-02-18 | 2011-03-08 | Angiochem Inc. | Aprotinin polypeptides for transporting a compound across the blood-brain barrier |
| US7557182B2 (en) | 2005-02-18 | 2009-07-07 | Angiochem Inc. | Molecules for transporting a compound across the blood-brain barrier |
| AU2006272405B2 (en) * | 2005-07-15 | 2013-02-07 | Angiochem Inc. | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| US8969310B2 (en) | 2005-07-15 | 2015-03-03 | Angiochem Inc. | Potentiation of anticancer agents |
| JP2015163641A (en) * | 2005-07-15 | 2015-09-10 | アンジオケム インコーポレーティッド | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| US9713646B2 (en) | 2005-07-15 | 2017-07-25 | Angiochem Inc. | Potentiation of anticancer agents |
| WO2007009229A1 (en) * | 2005-07-15 | 2007-01-25 | Angiochem Inc. | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| US8710013B2 (en) | 2008-04-18 | 2014-04-29 | Angiochem Inc. | Pharmaceutical compositions of paclitaxel, paclitaxel analogs or paclitaxel conjugates and related methods of preparation and use |
| US8828925B2 (en) | 2008-10-15 | 2014-09-09 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| US8921314B2 (en) | 2008-10-15 | 2014-12-30 | Angiochem, Inc. | Conjugates of GLP-1 agonists and uses thereof |
| US9914754B2 (en) | 2008-12-05 | 2018-03-13 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| US8853353B2 (en) | 2008-12-17 | 2014-10-07 | Angiochem, Inc. | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| US9173891B2 (en) | 2009-04-20 | 2015-11-03 | Angiochem, Inc. | Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog |
| US9161988B2 (en) | 2009-07-02 | 2015-10-20 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| EP2864349A4 (en) * | 2012-06-20 | 2016-02-24 | Univ California | DYNAMIC BIOMEMETICAL CATALYST OF SYNZYME TYPE, CATALYSIS, AND CATALYTIC SYSTEMS |
| US9976133B2 (en) | 2012-06-20 | 2018-05-22 | The Regents Of The University Of California | Synzymes |
| US10980892B2 (en) | 2015-06-15 | 2021-04-20 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
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| R002 | Refusal decision in examination/registration proceedings | ||
| R082 | Change of representative |
Representative=s name: GILLEN, CLEMENS, DIPL.-CHEM. DR. RER. NAT., DE Representative=s name: HAEUSLER, LARS, DIPL.-BIOCHEM. DR. RER. NAT., DE |
|
| R016 | Response to examination communication | ||
| R082 | Change of representative |
Representative=s name: GILLEN, CLEMENS, DIPL.-CHEM. DR. RER. NAT., DE |
|
| R016 | Response to examination communication | ||
| R002 | Refusal decision in examination/registration proceedings | ||
| R006 | Appeal filed | ||
| R003 | Refusal decision now final | ||
| R011 | All appeals rejected, refused or otherwise settled |