| Let's Read Together! The
table below gives examples of patent expirations, loss of
protection for pharma products. Pharma products may be protected by more
than a single patent. If complete, the expiration could give priority in coming
inventions to further
directions of:
original
small molecules and generic followers... original
biotech products and biosimilar followers... nucleotide sequences...
small molecules conjugated to
target specific single chain proteins...
Considerations in view of personalized medicine: Limits
in application of small molecules and biotech
pharma products: safety and efficacy?
Limits
in application of Bio and Pharma 3D printing
techniques: safety and efficacy?
Further
developments? Synthetic
biology? Diagnostic aspects? |
.......................
|
Patent
expiration / pharma industry / March-May, 2016
source: drugpatentwatch.com
|
|
| Patent
No Filing* Priority** Expiration*** |
Notes |
| US
6,423,342 04-05-1999 * 02-03-1995** 01-03-2016*** ZELAPAR selegiline hydrochloride tablet Valeant Pharmaceuticals Intl. |
Phenthylamine derivative, an
additional component to
the Levodopa/Carbidopa therapy for the symptomatic treatment
of Parkinson's disease. It acts by inhibiting neurotransmitter
degradation [irreversible
inhibition of
monoamine oxidase (MAO-B)], enhancing thus dopaminerg activity of basal
ganglia. Bio perspective:
|
| US
5,840,763 US 5,916,893 01-09-1995*
01-03-2016***
FAMVIR famciclovir tablet Novartis |
For
the symptomatic treatment of Herpes
simplex virus (HSV-1, HSV-2) and Varicella zoster virus (VZV)
infections. It acts by inhibiting viral DNA polymerase in infected
cells, reducing thus the propagation of viruses.
Bio perspective: VZV vaccine (attenuated living viruses) approved by the end of the year 2015 |
| US 6,034,267 08-03-1996* 10-03-1995** 08-03-2016*** METVIX methyl aminolevulinate
hydrochloride cream Galderma Labs. L.P. |
Photosensitizer
(photodynamic) cream for the photochemotherapeutic treatment of keratosis
actinica (k. solaris) with the help of red
range light (Aktilite CL128) provoking cell necrosis, apoptosis by
the generation of cytotoxic reactive intermediates, in immunocompetent patients.
Bio perspective: photodynamic creams acting on the same principles (generics). |
| US 5,756,541 11-03-1996* 11-03-2016*** VISUDYNE verteporfin powder, solution Valeant Pharm. Luxembourg S.a.r.l. |
Benzoporphyrin
derivative, an adjunct for the photodynamic treatment of fungal
infections in the eyes (histoplasmosis), for pathological
myopia, for macula degeneration. Its combination with laser
phototherapy results in the liberation of cytotoxic reactive oxygen
intermediates, the harmful effects to
endothelial cells, thus restricting subfoveal choroidalis
neovascularisation.
Bio perspective: photodynamic generics acting on the same principles. |
| US 5,881,926 30-08-1993* 11-03-1993** 16-03-2016*** FLO-PRED prednisolone acetate oral suspension Taro Pharm. Ind. Ltd. |
Antiinflammatory steroid (see: steroid action). Bio perspective: targeted biotherapy (e.g. biosimilar recombinant antibodies), further search for natural substances. |
| US 5,854,290 21-09-1995* 21-03-2016*** INTUNIV guanfacine hydrochloride tablet Shire US Inc. |
Selective
agonist to central alpha2A-adrenergic
receptors, an antihypertensive sympatholytic drug (decrease in impulses
released from brain stem vasomotor center resulting in the
decrease of peripheral resistance, sympathetic tone and, blood
pressure).
Bio perspective: protein scaffold for the delivery of therapeutic small molecules. |
| US
5,811,436 30-01-1995* 03-02-1994** 22-03-2016*** PAXIL paroxetine hydrochloride tablet Apotex Technologies Inc. |
Phenylpiperidine type
antidepressant for the selective inhibition of serotonin transporters,
leading to
the blockade of serotonin reuptake, ending up in
prolonged
neurotransmission.
Bio perspective: biotherapy targeting mTOR (serine/threonine kinases) signaling pathways (influence on cell metabolism, here: on synthesis of synaptic proteins > on translation initiation). |
| US 5,886,039 07-06-1995* 02-09-1988** 23-03-2016*** MUSE alprostadil urethral suppository Meda Pharmaceuticals |
Suppository
for transurethral entry, containing prostaglandin
E1 alike eicosanoid. In contrast to the indirect effects of
PDE5
inhibitors, it directly results smooth muscle
relaxation
together with vasodilation of arteria
cavernosa (correction
of erectile dysfunction caused by damages in blood vessel wall,
deficiencies in blood circulation and/or
metabolism).
Developed formulation: gel for transdermal absorption. Bio perspective: alternative care. |
| US 6,387,946 US 6,372,780 US 6,331,635 28-04-1998*
26-03-1996**
26-03-2016***
JEVTANA KIT cabazitaxel infusion, solution Sanofi Aventis US |
Cytostatic drug, taxol
derivative preventing the dynamic assembly of cytoskeletal microtubules,
hence inhibiting cell division. Bio perspective: biotherapy based on anomaly-related biomarker research (development of tumor specific antibodies, of oncolytic viruses, of vaccines ). |
| US 6,489,329 20-04-2001* 08-04-1996** 08-04-2016*** ZYRTEC-D 12 HOUR cetirizine hydrochloride; pseudoephedrine hydrochloride tablet J & J Consumer Inc. |
A two-in-one combination of
components for the alleviation of the symptoms in allergic and viral rhinitis.
Component cetirizine is an
antagonist to H1 receptors and an inverse agonist to H1
signalling pathways. Component pseudoephedrine is an agonist
to alpha-adrenergic
receptors.
The latter acts by releasing norepinephrine of presynaptic vesicles into the synaptic cleft where primarily alpha-adrenergic receptors are stimulated. The stimulus results in vasoconstriction leading to decongestion of the nose and sinuses. Bio perspective: pre-seasonal preventive care with antihistamines acting on H1 receptors and H1 signalling pathways and, in an independent way suppressing gene expression of histidine decarboxylase, the enzyme regulating histamine synthesis. |
| US
RE40183
03-06-2005* 04-08-1994** TYGACIL tigecycline iv. infusion PF Prism C.V. |
Tetracyclin
derivative broad spectrum antibiotic with effects on Gram
positive and Gram negative bacteria, too. Due to the emerging
global spread of antibiotic resistance, further inventions are urged
for the translation of inventive novelties into clinical practice.
Bio-perspective: synthetic and semisynthetic new substances. |
| US 5,998,380 US 6,503,884 US 7,498,311 13-10-1995* 09-11-1999* 06-01-2006* 13-10-1995** 13-04-2016*** TOPAMAX topiramate capsule, tablet pediatric use Janssen Pharmaceuticals Inc. |
Anticonvulsant
sulfamate derivative for the prophylaxis of
periodically recurring, throbbing migraine pain
(of non-epileptic patients). Currently, the development of migraine is
traced back to the stimulated interactions of cranial nerve V
and
the cerebral cortex, and/or to
neurovascular reasons manifesting in pain waves with or without aura.
Bio-perspective:
|
| US 5,869,082
12-04-1996*
16-04-2016***
NITROMIST nitroglycerin sublingual aerosol
Mist Pharmaceuticals LLC |
Bypassing first pass effect,
buccal
transmucosal accelerated delivery of nitroglycerin (GTN) dissolved in
non-polar hydrocarbon, formulated in a biocompatible,
hydrocarbon-miscible propellent. When in use, the propellent
evaporates, the active substance in form of small droplets
create
a coat on the buccal mucosal (sublingual) surface and the
penetration of the
drug follows, resulting in systemic greater bioavailability compared to
delivery
per os. As an organic nitrate,
nitroglycerin (GTN) is an antihypertensive substance
with vasodilatory effects
(NO/cGMP signalling pathways mediated smooth muscle relaxation in
the blood vessel wall). Indication of use: relief/prophylaxis
of acute angina attacks in CAD
patients.
Bio-perspective:
|
| US 6,022,562 17-10-1995* 18-10-1994** 17-04-2016*** COREG CR calvedilol phosphate extended release capsule SB Pharmco Puerto Rico, Inc. |
Technological
solution comprising drug (nutrient) carrier polymer microcapsules
formulated in
tablets/powder/gelatin capsules for per os
delivery of
extended release substances (preferred residence
time in small intestine is 8h - 24h).
In case of nonselective beta-adrenoceptor (beta1-, beta2-, + alpha1-adrenoceptor) antagonist and slightly antioxidant COREG CR/calvedilol, the technology serves for the controlled management of chronic heart failure (systolic anomalies) and hypertension, supplementing the treatment with thiazide type diuretics, with ACE inhibitors, or with digitalis. Bio-perspective:
|
| US
5,898,030 17-06-1994* 27-04-2016*** ZORBTIVE SEROSTIM SAIZEN somatropin recombinant sc. / im. injection EMD Serono, Inc. |
Technological
description of the composition of rHGH (recombinant human growth
hormone) stabilized by the addition of
saccharose/saccharose-mannitol.
Indication: management of congenital or acquired HGH (somatotropin) deficiencies (pediatric, adult), maintenance of conditions with injured alimentary (e.g. short bowel syndrome) and anabolic pathways. Bio-perspective:
|
| US 5,900,424 08-07-1994* 09-07-1993** 04-05-2016*** PRILOSEC PRILOSEC OTC omeprazole magnesium capsule/granule delayed release AstraZeneca Pharmaceuticals LP |
Technological
description of the pharmacological preparation of (class
sulfinylbenzimidazoles) omeprazole magnesium salt, with emphasis on
optimizing its assembly, purification, and crystallization.
Indication: weak base omeprazole binds selectively to (activated) H+, K+-ATPase, the enzyme responsible for the last step in acid secretion of parietal cells in the gastric mucosa (proton pump inhibition). By inhibiting acid secretion in a dose dependent manner, the acid induced mucosa erosion (e.g. gastroesophageal reflux disease, Helicobacter pylori associated gastric ulcer, enhanced secretion of gastric acid in Zollinger-Ellison syndrome) is ameliorated. Bio-perspective: omeprazole has already long history, and, in our days too, is considered a well tolerated preparation.
|
| CA 2 191 475 06-05-1996* 08-05-1995** 06-05-2016*** A DRUG, CONTAINING ONE OR MORE PLASMA DERIVATIVES quality-assurance method Baxalta Inc. USA, Baxalta GmbH |
Dual-target (=
oligo primers for different target sequences) Southern blot-PCR
(DTS-PCR) and laser induced fluorescent
PCR tests (with fluorescent labelled oligos > LIF-PCR)
for the detection of haematogen viruses HAV, HBV, HCV, HIV,
HPVB19
in starting material, intermediate products, and final
products of
manufacturing blood plasma and blood plasma derivatives (e.g. albumin,
immunoglobulins, blood clotting components), meanwhile serological standard methods and procedures
for virus removal/virus inactivation (nanofiltration,
heat-inactivation, enzymatic treatments, organic solvents, surfactants,
chromatography, ultracentrifugation) are retained.
Endpoint PCR tests
mentioned above target sequences in conserved regions of the viral
genome.
Bio-perspective: in current European Guideline (2015) the necessity of serological and nucleic acid based tests (NAT) in quality assurance of manufacturing blood plasma and blood plasma derivatives, are emphasized. Development of NAT/PCR method in detecting the presence of viruses:
|
| CA 2 223 694 07-05-1996* 07-06-1995** 07-05-2016*** ISOLATED NUCLEIC ACID MOLECULES, PEPTIDES WHICH FORM COMPLEXES WITH MHC MOLECULE HLA-A2 AND USES THEREOF immunotechnology for diagnostic and therapeutic purposesLudwig Institute for Cancer Research U.S.A. // Inserm France |
Isolation of HLA-A2 (human
leukocyte antigen ≡ MHC2A) coding nucleic acid
sequences and/or tumor rejection antigen
(TRA, here: melanoma antigen) precursor/peptide coding
defined
nucleic acid sequences > integration into expression vectors
(bacterial/viral) > transformation/transfection of prokaryotic
(e.g.
E.coli) or eukaryotic (e.g. CHO,
COS, melanoma) cells > in vitro culturing
of autologous cytolytic T
lymphocytes (CTLs) specific for the HLA-A2-peptide expression complex.
Options
for application:
HLA (≡ MHC) presented immunopeptidome analysis:
application of the robust SWATH mass spectrometry
for
the reproducible detection and quantitation of immunopeptides specific
for pathogens and tumors, aiming the elaboration of
personalized
immunotherapy.
|
| US 5,955,488 US 6,063,802 US 5,854,270 28-04-1998* 22-11-1994** 14-05-2016*** 28-01-1998* 22-11-1994** 14-05-2016*** 20-11-1995* 22-11-1994** 20-05-2016*** ZOFRAN ODT ondansetron free base in freeze-dried form ZOFRAN ODT ondansetron free base in freeze-dried form ZOFRAN ondansetron hydrochloride liquid Novartis Pharmaceuticals Corp. |
Antiemetic
drug for preventing nausea/vomiting, mainly in surgical and/or
chemotherapeutical and/or radiological care of tumor patients. A
selective antagonist for serotoninergic
5-HT3 receptors (at nerve endings of peripheral nervus vagus,
at
chemoreceptor trigger zone of central area postrema - medulla
oblongata). The afferent emetogenic pathway to dampen is: antineoplastic substance > serotonin release from small intestine enterochromaffin cells > degenerative changes in the gastrointestinal tract > 5-HT3 mediated stimulation of nervus vagus and nervus splanchnicus fibers > impulses reaching the medullar vomiting center // impulses reaching the chemoreceptor trigger zone of area postrema. Bio-perspective: personalized regimens for antiemetic therapy related to antineoplastic medication of high, medium, and low (or minimal) emetogenic potential. |
| US 5,567,817 01-05-1995* 02-02-1990** 24-05-2016*** VFEND voriconazole oral suspension iv. injection tablet PF PRISM C.V. |
Synthetic triazole antimicotic
(fungistatic ≡ inhibition of growth);
administered mainly in Aspergillus, Candida, Fusarium
and
Scedosporium fungal infections
(aspergillosis, esophageal
candidiasis...).
Mechanism of action > restraining synthesis of cell membrane
component ergosterol by the selective inhibition of the enzyme CYP450 dependent 14-alpha
lanosterol demethylase > disruption in cell
membrane integrity, ending up in changes of permeability, of survival
capacity. Bio-perspective: a new objective is the dispruption of cell wall for the exploration of correspondance between cell wall and signaling pathways in order to construct substances efficient and specific in interfering with fungal vitality. |
| CA 2 226 488 28-05-1996* 17-07-1995** 28-05-2016*** POLYSACCHARIDE GEL COMPOSITION technology-method for extended/continuous release of bioactive substances Q-Med AB Sweden |
Preparation
of water soluble biocompatible polisaccharide gel by crosslinking
glucose amino glycan (hyaluronate) units. Crosslinking
(aldehydes/epoxides/...) happens in two phases. First phase: to reach a
pre-gel status. At this stage the gelling process is halted by steric
inhibition, i.e. by diluting the system. This stage favours the
inclusion (by dispersing/dissolving) of the bioactive component chosen.
Second phase: suspension of steric inhibition by concentration, and the
ongoing crosslinking leads to a visco-elastic gel, the depot vehicle of
bioactive substances included (hormones, cytokines, vaccines,
tissue-augmenting components, components in wound care ...). Bio-perspective along with applications above: electronic sensors embedded in biocompatible hydrogel matrix > use on body surfaces as bandage in 'interactive' care for wounds and injuries > use by delivery into the body to perform sensory functions in metabolism, neuronal activities. |
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