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Controlled Release Formulations Of Dronedarone

Abstract: The present invention relates to controlled release formulation of dronedarone of pharmaceutically acceptable salts, esters, metabolites, prodrugs or enantiomers thereof and controlled release polymers. The use of controlled release formulations of Dronedarone would improve the bioavailability and the patient compliance with reduction in number of dosages to be taken per day.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
17 August 2010
Publication Number
27/2013
Publication Type
INA
Invention Field
PHARMACEUTICALS
Status
Email
Parent Application

Applicants

LUPIN LIMITED
159 CST ROAD, KALINA, SANTACRUZ (EAST), MUMBAI- 400 098, STATE OF MAHARASHTRA, INDIA AND ALSO HAVING A PLACE OF BUSINESS AT 1/1, SASHI SHEKHAR BOSE ROAD, KOLKATA - 700 025, STATE OF WEST BENGAL, INDIA

Inventors

1. DESHMUKH, ASHISH, ASHOKRAO
LUPIN LTD. (RESEARCH PARK), 46A/47A, NANDE VILLAGE TALUKA MULSHI, PUNE -411042, MAHARASHTRA
2. BHUTADA, PRAVIN, MEGHRAJJI
LUPIN LTD. (RESEARCH PARK), 46A/47A, NANDE VILLAGE TALUKA MULSHI, PUNE -411042, MAHARASHTRA
3. CHANDRAN SAJEEV
LUPIN LTD. (RESEARCH PARK), 46A/47A, NANDE VILLAGE TALUKA MULSHI, PUNE -411042, MAHARASHTRA
4. KULKARNI SHIRISHKUMAR
LUPIN LTD. (RESEARCH PARK), 46A/47A, NANDE VILLAGE TALUKA MULSHI, PUNE -411042, MAHARASHTRA

Specification

Field of the Invention: The present invention relates to controlled release formulation for the delivery 01 an anti-arrhythmic drug. The controlled release formulation comprises of dronedarone or pharmaceutically acceptable salts, esters, metabolites, prodrugs or enantiolTiers thereof. Background of the Invention: Cardiac arrhythmia is a. term for any large and heterogeneous group of conditions Iti which there is abnormal electric activity in the heart. An arrhythmia is a disordei' of the heart rateheart rate (pulse) or heart rhythm, such as beating too fast (tachycardia), too slow (bradycardia), or irregularly. Arrhythmias can be lifethreatening medical emergencies which can result in cardiac arrest and sudden death. Normally, the four chambers of the heart contract in very specific and coordinated manner. The electrical impulse that signals the heart to contract in a synchronizeo manner begins in the sinoatrial node (SA node) which is heart's natural pacemaker The signal leaves the SA node and travels through the two upper chambers (atna: Then the signal passes through the atrioventricular node (AV node). Finally it passes through the lower chambers (ventricles). This path enables the chambers to contract in a coordinated fashion. Problems can occur anywhere along this conduclion system, causing various arrhythmias. The examples include: Bradycardia - a slow heart rate due to problems with the SA node's pacemaker ability, or an interruptio!i In energy movement (conduction) through the natural electrical pathways of the hedrt Supraventricular tachycardia - a fast heart rate that originates in the upper chamhers (atria). The most common are atrial fibrillation or flutter (a rapid heart rate that is not regular).and atrioventricular nodal reentry tachycardia (AVNRT). VentricLiiar tachycardia - a fast heart rate that originates in the lower chambers (ventricles). The method of cardiac rhythm management depends firstly on whether or not U'le affected person is stable or unstable. Treatments may include physical maneuvers medications, electricity conversion, or electro or cryo cautery. When an arrhythmia IS 2 serious, urgent treatment may be required to restore a normal rhythm. This !flay include: electrical "shock" therapy (defibrillation or cardioversion), implantinq a temporary pacemaker to interrupt the arrhythmia medications given through a vein (intravenous). Medications are generally used to prevent and/or manage arrhythmia There are many classes of antiarrhythmic medications, with different mechanisms of action which include Sodium Channel Blockers (Class I) e.g. Class IA -QuinieJIlile (Quinidex), Procainamide (Pronestyl), Disopyramide (Norpace); Class IB- Lidoccliine (Xylocaine), Tocainide (Tonocard), Mexiletine (Mexitil); Class IC- Encairwje (Enkaid), Flecainide (Tambocor); Beta-Adrenergic Blockers (Class II)-Propranolol (Inderal), Acebutolol (Sectral), Esmolol (Brevibloc), Sotalol (Betapace); Drugs "hat Prolong Repolarization (Class 111)- Dronedarone (Multaq), Amiodarone (Cordaror1e) Calcium Channel Blockers (Class IV)- Verapamil (Calan, Isoptin), Diltiazem (Cardizem), Mebefradil (Posicor); Miscellaneous- Adenosine (Adenocard), Digoxin (Lanoxin). Dronedarone hydrochloride is N-{2-butyl-3-[4-(3-dibutylaminopropoxy) benz:l\/l) benzofuran-5-yl} methane sulfonamide, hydrochloride. The effects of Dronedarone most likely result from its electrophysiological properties belonging to all four Vaughan-Williams classes. Dronedarone is a multichannel blocker inhibiting the potassium currents (including IK (Ach), IKur, IKr, IKs) and thus prolonging cardiac action potential and refractory periods (Class III). It also inhibits the sodium currents (Class Ib) and the calcium currents (Class IV). It non competitively antagonizes adrenergic activities (Class II). Dronedarone works by altering currents passing through potassium, sodium, and calcium channels, theret)y 3 prolonging conduction in the heart. This helps maintain a regular heart rhythm or sinus rhythm and slows the heart rate. The available dosage for Dronedarone is 400 mg oral tablet to be administered tWice a day with meals. Dronedarone hydrochloride (Multaq®; Sanofi-Aventis) was approved to reduce the risk of cardiovascular hospitalization in patients Wlttl paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors (i.e., age > 70 hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ~ 50 nnrn or left ventricular ejection fraction [LVEF] < 40%), who are in sinus rhythm or wrlO will be cardioverted). Dronedarone is also found to be useful in prevention of stnJke or transient ischemic attack, prevention of permanent atrial fibrillation, prevention of cardioversion, regulating potassium levels in blood, for prevention of caroii:1C arrhythmia and increased creatinine level, reducing death rate after infarction w'ld reducing death rate after infarction. The primary advantage of dronedarone is Its comparatively lower side- effect profile vis-a-vis amiodarone. Due to hlqt1 presystemic first pass metabolism the absolute oral bioavailability is only 4 (fasting) which increases to approx. 15% when administered with a high fat meal. US5223510 assigned to Sanofi discloses dronedarone specifically. US7:323493 assigned to Sanof; Aventis relates to a solid pharmaceutical composition for oral administration characterized in that it comprises a benzofwan derivative with antiarrhythmic activity, or one of the pharmaceutically acceptable salts thereof, as an active principle, and a pharmaceutically acceptable noniol!lc hydrophilic surfactant optionally in combination with one or more pharmaceutical excipients. US 2007/0243257 filed by Sanofi Aventis relates to a solid pharmaceutical composition comprising a solid dispersion containing at least one active principle and a pharmaceutically acceptable polymer matrix, characterized in that selid 4 pharmaceutically acceptable polymer matrix comprises a blend of (i) polydextrose if' the form of a continuous polydextrose phase, in order to promote the disintegration of the composition in an aqueous medium, and (ii) at least one polymer other than polydextrose, in the form of a continuous phase of this polymer, whereby It'le polydextrose is in a concentration of at least 20 wt % and the at least one polymer other than polydextrose is in a concentration of at least 20 wt % in relation to line total weight of said pharmaceutically acceptable polymer matrix. US 2008/0139645 filed by Sanofi Aventis relates to a solid pharmaceutical composition for oral administration characterized in that it comprises a benzofuran derivative with antiarrhythmic activity, or one of the pharmaceutically acceptable salts thereof, as an active principle, and a pharmaceutically acceptable noniol1lc hydrophilic surfactant optionally in combination with one or more pharmaceutlcai excipients. Although number of approaches have been disclosed in the prior art for preparinq a formulation comprising dronedarone none describe a controlled relase formulation of dronedarone. There exists a need for controlled release formulation of Dronedarone which controls the release of Dronedarone in such a manner that therapeutically effective concentration is maintained in the blood for an extended period of tlnle keeping the drug concentration in the blood substantially constant. Dronedarone has low solubility in aqueous media andl or at low pH, also at higher pH conditioll it precipitates out. As a result it has low in-vivo bioavailability. The use of controlle(j release formulations of Dronedarone would improve the bioavailability and rile patient compliance with reduction in number of dosages to be taken per day. Summary of the Invention: One embodiment discloses a controlled release formulation of dronedarone comprising: dronedarone, a controlled release polymer and pharmaceuticallv acceptable excipients. 5 Another embodiment discloses a controlled release formulation comprising: (i) Dronedarone, controlled release polymer and pharmaceutically acceptable excipients, (ii) Controlled release coating. Another embodiment discloses a controlled release formulation of dronedarone comprising dronedarone along with pharmaceutically acceptable excipients and controlled release coating. Another embodiment discloses a controlled release formulation comprising: (i) Dronedarone and pharmaceutically acceptable excipients, (ii) One or more coating optionally comprising dronedarone. Another embodiment discloses a controlled release formulation of dronedarone wherein the controlled release polymer used may be bioadhesive. Brief Description of the Drawings: Drug release for examples 1, 7 and 12 are reproduced in the attached Fig. 1 Detailed Description of the Invention: A controlled release formulation of dronedarone or pharmaceutically acceptatJle salts, esters, metabolites, prodrugs or enantiomers thereof and pharmaceutically acceptable excipients. The term "formulation" as used herein refers to the drug with pharmaceutically acceptable excipients. This includes orally administrable formulations as well as formulations administrable by other means. "Controlled release formulation" as used herein are those whose drug release characteristics of time course and/or location are chosen to accomplish therapeutic 6 or convenience objectives not offered by conventional, immediate release dosa~Je forms. "Controlled release formulation" or dosage forms which exhibit a "controlled release' used herein is defined to mean formulations that release the drug at a controlled rate and provide plasma concentrations of the drug that remain controlled with tirne within the therapeutic range of the drug over a 24-hour period. "Controlled release' is defined to mean release of the drug gradually or in a controlled manner per unit time. For example, the controlled rate can be a constant rate providing plasma concentrations of the drug that remain invariant with time within the therapeutic range of drug over at least a 24-hour period. The term controlled release formulation may be used interchangeably Wlttl prolonged release formulation, programmed release formulation, timed release formulation, modified release formulation, site specific release formulation, sustained release formulation, extended release formulation, slow release formulatbi pulsatile release formulation, delayed release formulation. The controlled release formulations can be orally disintegrating extended release formulation, osmotic dosage form, bioadhesive formulation, gastroretentive formulation and other such dosage forms. As used herein the term dronedarone includes all forms of dronedarone I' pharmaceutically acceptable salts, esters, solvates, hydrates, metabolites, prodru9s or isomers thereof. The most preferred form is dronedarone hydrochloride. The controlled release formulation may be in the form of tablets (single layerec] tablets, multilayered tablets, mini tablets, bioadhesive tablets, floating formulation caplets, matrix tablets, tablet within a tablet, mucoadhesive tablets, modified releasl:; tablets, pulsatile release tablets, gastroretentive tablets and timed release tablets: pellets, beads, granules, spheroids, particles, compact, powders, capsules 7 microcapsules, tablets in capsules, microspheres, matrix formulations, fj(j microencapsulation. The term "pharmaceutically-acceptable excipients" as used herein includes cny physiologically inert, pharmacologically inactive material known to one skilled in tile art, which is compatible with the physical and chemical characteristics Oronedarone. One embodiment discloses a dronedarone, controlled release excipients. controlled release formulation polymer and pharmaceutically comprisiilg acceptaule The controlled release formulation of dronedarone may contain one or more tha r one controlled release polymer. Other embodiment discloses a controlled release formulation compris dronedarone having particle size (090) less than 100 microns. Preferably the partkle size (090) of dronedarone is less than 60 microns and more preferably particle s .?t? (090) less than 30 micron. The controlled release polymer may be selected from water soluble polymer, water insoluble polymer, waxy material or combination thereof. The water soluble polymer may be selected from alkyl celluloses such as mett, cellulose; hydroxyalkyl celluloses, for example, hydroxymethyl cellulose hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxybutyl cellulosl' hydroxyalkyl alkyl celluloses such as hydroxyethyl methyl cellulose ard hydroxypropyl methyl cellulose; sodium or calcium carboxymethyl cellulose, meth'! ethyl cellulose, ethylhydroxy ethylcellulose, carboxyalkyl cellulose esters; carbomers ; glycerol fatty acid esters, sorbitan esters, lecithins, other natural, semi-synthetic, r synthetic di-, oligo-, and polysaccharides such as galactomannans, tragacanth, agel! 8 guar gum, gum arabic, pectin, acacia, karaya, locust bean gum, xanthan 9 rn pullulan, collagen, casein, carrageenan, aligns, polycarbophil, ammonia alginate sodium, calcium, potassium alginates, propylene glycol alginate, scleroglucan nd polyfructans, maltodextrin; methacrylate copolymers; polyvinyl alcoiol polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate combinations of polyvinyl alcohol and polyvinylpyrrolidone; and polyalkylene OXij8S such as polyethylene oxide and polypropylene oxide and copolymers of ethylene oxide and propylene oxide, carboxyvinyl polymers, sodium alginate, sodlurn hyluronate, sodium carmellose, calcium carmellose, sodium carboxymethyl starch gelatin, starch, crosslinked starch, microcrystalline cellulose, ceratonia, chitin poly(hydroxyalkyl methacrylate), polyvinyl alcohol having a low acetate residuE]! a swellable mixture of agar and carboxymethyl cellulose, crosslinked polyvinyl alconoi and poly N-vinyl-2-pyrrolidone and mixtures and blends thereof. Water insoluble polymer may be selected from cellulose acylate; cellulose eO! ether; cellulose diacylate; cellulose triacylate; cellulose acetate; cellulose diacetate cellulose triacetate; mono-, di- and tricellulose alkan, mono-, di- and tricelluluse aroyl; ethyl cellulose; cellulose acetate; cellulose acetate butyrate; cellulose ace':ate phthalate; cellulose acetate trimellitate; glyceryl monooleate; glyceryl monosteardte glyceryl palmitostearate; polyvinyl acetate phthalate; hydroxypropylmethylcelluluse phthalate; hydroxypropylmethylcellulose acetate succinate; poly(alkyl methacrylate) poly (vinyl acetate); poly vinyl alcohols; polyacrylamide derivatives ammonlc methacrylate copolymers, poly acrylic acid and poly acrylate and methacry:,Cite copolymers, aminoacryl-methacrylate copolymer, polyvinyl acetaldiethylarnflo acetate, copolymers of maleic anhydride and styrene, ethylene, propylene Dr isobutylene, polyacrylamides, polyox( polyethylene oxides), diesters of polygluc:Hl cellulose butyrate, cellulose propionate, shellac, chitosan, oleyl alcohol, ze n hydrogenated castor oil and the like. Waxy material may be selected from carnauba wax; beeswax; chinese wax spermaceti; lanolin; bayberry wax; white wax; yellow wax; candelilla w x 9 microcrystalline wax; castor wax; esparto wax; Japan wax; jojoba oil; cotton seec Dr corn oil, hydrogenated cotton seed oil, ouricury wax; rice bran wax; ceresin wa>:es montan wax; ozokerite; peat waxes; paraffin wax; polyethylene waxes; ,1ilej polyglycerol fatty acid esters. One embodiment discloses a controlled release formulation of dronedar:iIle comprising: dronedarone, a controlled release polymer and pharmaceuticdilV acceptable excipients. Another embodiment discloses a controlled release formulation of dronedarurle wherein the controlled release polymer used may be bioadhesive. The bioadhesive polymers may be selected from proteins (e.g., hydrophilic protei S i such as carbomers, pectin, zein, modified zein, casein, gelatin, gluten, ser,un albumin and collagen; chitosan; oligosaccharides; polysaccharides such ciS cellulose, dextrans, tamarind seed polysaccharide, gellan, carrageenan, xanthdJ! gum, gum arabic, hyaluronic acid, polyhyaluronic acid, alginic acid and sodiun, alginate; glyceryl monooleate; polyamides;, polycarbonates; polyalkylenics polyalkylene glycols; polyalkylene oxides; polyalkylene terephthalates; polyvi alcohols; polyvinyl ethers; polyvinyl esters; polyvinyl halides; polyvinylpyrrolido!le polyglycolides; polysiloxanes; polyurethanes; polystyrene; polymers of acrylic B'ld methacrylic esters; polylactides; poly(butyric acid); poly(valeric acid); poly(lactide-cll glycolide); polyanhydrides; polyorthoesters; poly(fumaric acid); poly(maleic aCIO) poly(methyl vinyl ether/maleic anhydride); polycarbophil and blends or copolymers 01 mixtures thereof. The controlled release formulation may further contain one or more pharmaceuticcl Iy acceptable excipients such as binders; diluents; lubricants; disintegrating agenl::, glidants; stabilizers; osmotic agents; dissolution enhancing agents; and surface active agents. 10 Examples of binders include, potato starch; pregelatinized starch; modified steilch gelatin; wheat starch; corn starch; celluloses such as methyl cellul'lse hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, etllV cellulose and sodium carboxy methyl cellulose; hydroxypropyl Sta polymethacrylates; carbomers; natural gums such as acacia, alginic acid and !lua! gum; lactose (anhydrous, monohydrate, spraydried); liquid glucose; dextrin; SOCIWTl alginate; kaolin; povidone; syrup; polyethylene oxide; polyvinyl pyrrolidone; .J()ly vinyl alcohol; poly-N-vinyl amide; polyethylene glycol; sucrose; polydextrose; gelatin poly propylene glycol; tragacanth; ceratonia; glyceryl behenate; hydrogenc:.Itea vegetable oil; zein; castor oil; paraffin; higher aliphatic alcohols; higher alipb.Cltlc acids; long chain fatty acids; fatty acid esters; agar; chitosan; maltodeXlrlf! magnesium aluminum silicate; inulin and wax-like materials such as fatty alcohols fatty acid esters, fatty acid glycerides, hydrogenated fats, hydrocarbons, stearic ard copovidone; dextrates, sunflower oil and stearyl alcohol. Examples of diluents include microcrystalline cellulose; lactose, cellulose powdelea cellulose silicified, cellulose acetate, methyl cellulose, microcrystalline lactcse dibasic or tribasic calcium phosphate; saccharides; confectioner's supar compressible sugar; confectioner's sugar; sugar spheres; dextrates; dexl ,n dextrose; fructose; maltose; sodium chloride; lactitol; maltodextrin; mannitol sucrose; fructose; glyceryl palmitostearate; semithicone; Magnesium alumir13 hydroxypropyl starch; sodium starch glycolate; sodium starch glucolate; sodilllTI carboxymethylcellulose; carboxymethyl cellulose calcium; sodium carboxymethyl starch; ion-exchange resins such as polacrillin potassium; microcrystalline cellulose 11 starches and pregelatinized starch; formalin-casein; clays such as bentonitE' 0' veegum; guar gum; celluloses or cellulose derivatives; sodium alginate; calciunl alginate; alginic acid; chitosan; magnesium aluminum silicate ; colloidal silicon dioxide. The lubricants may be selected from Mg, AI, Ca or Zn stearate; polyethylene glyco' polyvinyl alcohol; glyceryl behenate; glyceryl monostearate; Glyce palmitostearate; potassium benzoate; sodium benzoate; mineral oil; sodium steary: fumarate; palmitic acid, myristic acid; stearic acid; hydrogenated vegetable CII! hydrogenated castor oil; talc; hydrogenated soybean oil; stearyl alcohol; leucrle sodium lauryl sulfate; ethylene oxide polymers; poloxamer; octyldodecanol; Sod.H1l stearyl fumarate and colloidal silica. The stabilizers may be selected from naturally occuring as well as synthetic phospholipids, their hydrogenated derivatives and mixtures thereof; organic aC!(Js like acetic acid, tartaric acid, citric acid, fumaric acid, lactic acid, and mixtures thereof sphingolipids and glycosphingolipids; physiological bile salts such as sodi !Tcholate, sodium dehydrocholate, sodium deoxycholate, sodium glycocholate (-1 sodium taurocholate; saturated and unsaturated fatty acids or fatty alcohu!s etho.xylated fatty acids or fatty alcohols and their esters and ethers; alkyla! polyether alcohols such as tyloxapol; esters and ethers of sugars or sugar alcoh()ls with fatty acids or fatty alcohols; acetylated or ethoxylated mono- and diglyceridc:s synthetic biodegradable polymers like block co-polymers of polyoxyethylene cHlO polyoxypropyleneoxide; ethoxylated sorbitanesters or sorbitanethers; amino acids polypeptides and proteins such as gelatine and albumin; or combination thereof. The glidants may be selected from magnesium trisilicate; powdered celluloi'.,e starch; talc; tribasic calcium phosphate; calcium silicate; magnesium silic81e magnesium trisilicate; colloidal silicon dioxide; and silicon hydrogels. 12 Dissolution enhancing agents may be selected from, but are not limited to, orgdll acids, inorganic acids or combination thereof. The organic acids include, but nol limited to citric acid, fumaric acid, malic acid, maleic acid, tartaric acid, succinic aCI() oxalic acid, aspartic acid, mandelic acid, glutaric acid, and glutamic acid. inorganic acids include but not limited to hydrochloric acid, phosphoric acid, nitriC acid, and sulfuric acid. The surface active agents used may be hydrophilic, hydrophobic or combinall esparto wax; Japan wax; jojoba oil; cotton seed oil, corn oil, hydrogenated cotten seed oil, ouricury wax; rice bran wax; ceresin waxes; montan wax; ozokerite; pedt waxes; paraffin wax; polyethylene waxes; and polyglycerol fatty acid esters an(] pharmaceutically acceptable excipients. 6. A controlled release formulation of dronedarone comprising (1) Dronedarone and pharmaceutically acceptable excipients and (2) Controlled release coating. 33 7. The controlled release formulation of claim 6 wherein the controlled rele:lse coating comprises of controlled release polymer. 8. The controlled release formulation of Claim 6 wherein the controlled relea~,e polymers includes hydrophilic polymers, hydrophobic polymers or waxes. 9. The controlled release formulation of Claim 6 wherein the controlled release coating may be functional coating, moisture barrier coating, enteric polym,:,nc coating, sustained release coating and the like. 10. A controlled release formulation of dronedarone comprising (1) Dronedarone and pharmaceutically acceptable excipients and (2) One or more coating optionally comprising dronedarone. 11. The controlled release formulation of claim 10 wherein one or more coatinu is selected from controlled release or enteric or immediate release. 12. The controlled release formulation of claim 10 wherein the coating comprses of water soluble polymer, water insoluble polymer, waxy material or combinat:o! thereof as exemplified in example 13 or 14.

Documents

Application Documents

# Name Date
1 924-KOL-2010-HearingNoticeLetter-(DateOfHearing-14-01-2020).pdf 2019-12-16
1 924-kol-2010-specification.pdf 2011-10-07
2 924-KOL-2010-FORM 3 [09-10-2019(online)].pdf 2019-10-09
2 924-KOL-2010-OTHERS-1.1.pdf 2011-10-07
3 924-kol-2010-gpa.pdf 2011-10-07
3 924-KOL-2010-FORM 3 [10-09-2019(online)].pdf 2019-09-10
4 924-kol-2010-form-3.pdf 2011-10-07
4 924-KOL-2010-FORM 3 [10-04-2019(online)].pdf 2019-04-10
5 924-kol-2010-form-2.pdf 2011-10-07
5 924-KOL-2010-FORM 3 [06-10-2018(online)].pdf 2018-10-06
6 924-kol-2010-form-1.pdf 2011-10-07
6 924-KOL-2010-CLAIMS [25-07-2018(online)].pdf 2018-07-25
7 924-KOL-2010-FORM 1-1.1.pdf 2011-10-07
7 924-KOL-2010-FER_SER_REPLY [25-07-2018(online)].pdf 2018-07-25
8 924-KOL-2010-OTHERS [25-07-2018(online)].pdf 2018-07-25
8 924-kol-2010-description (provisional).pdf 2011-10-07
9 924-kol-2010-correspondence.pdf 2011-10-07
9 924-KOL-2010-FORM 3 [12-04-2018(online)].pdf 2018-04-12
10 924-KOL-2010-CORRESPONDENCE-1.2.pdf 2011-10-07
10 924-KOL-2010-FER.pdf 2018-01-25
11 924-KOL-2010-CORRESPONDENCE-1.1.pdf 2011-10-07
11 Form 13 [15-09-2016(online)].pdf 2016-09-15
12 924-KOL-2010-FORM 5.pdf 2011-10-17
12 Other Document [15-09-2016(online)].pdf 2016-09-15
13 924-KOL-2010-(13-12-2013)-CORRESPONDENCE.pdf 2013-12-13
13 924-KOL-2010-FORM 2-1.1.pdf 2011-10-17
14 924-KOL-2010-(13-12-2013)-FORM-3.pdf 2013-12-13
14 924-KOL-2010-DRAWINGS.pdf 2011-10-17
15 924-KOL-2010-(08-05-2012)-CORRESPONDENCE.pdf 2012-05-08
15 924-KOL-2010-DESCRIPTION (COMPLETE).pdf 2011-10-17
16 924-KOL-2010-(08-05-2012)-OTHERS PCT FORM.pdf 2012-05-08
16 924-KOL-2010-CORRESPONDENCE-1.3.pdf 2011-10-17
17 924-KOL-2010-AMANDED CLAIMS.pdf 2011-10-17
17 924-KOL-2010-(19-10-2011)-CORRESPONDENCE.pdf 2011-10-19
18 924-KOL-2010-(19-10-2011)-FORM 3.pdf 2011-10-19
18 924-KOL-2010-ABSTRACT.pdf 2011-10-17
19 924-KOL-2010-(19-10-2011)-FORM 3.pdf 2011-10-19
19 924-KOL-2010-ABSTRACT.pdf 2011-10-17
20 924-KOL-2010-(19-10-2011)-CORRESPONDENCE.pdf 2011-10-19
20 924-KOL-2010-AMANDED CLAIMS.pdf 2011-10-17
21 924-KOL-2010-(08-05-2012)-OTHERS PCT FORM.pdf 2012-05-08
21 924-KOL-2010-CORRESPONDENCE-1.3.pdf 2011-10-17
22 924-KOL-2010-(08-05-2012)-CORRESPONDENCE.pdf 2012-05-08
22 924-KOL-2010-DESCRIPTION (COMPLETE).pdf 2011-10-17
23 924-KOL-2010-DRAWINGS.pdf 2011-10-17
23 924-KOL-2010-(13-12-2013)-FORM-3.pdf 2013-12-13
24 924-KOL-2010-(13-12-2013)-CORRESPONDENCE.pdf 2013-12-13
24 924-KOL-2010-FORM 2-1.1.pdf 2011-10-17
25 924-KOL-2010-FORM 5.pdf 2011-10-17
25 Other Document [15-09-2016(online)].pdf 2016-09-15
26 924-KOL-2010-CORRESPONDENCE-1.1.pdf 2011-10-07
26 Form 13 [15-09-2016(online)].pdf 2016-09-15
27 924-KOL-2010-CORRESPONDENCE-1.2.pdf 2011-10-07
27 924-KOL-2010-FER.pdf 2018-01-25
28 924-kol-2010-correspondence.pdf 2011-10-07
28 924-KOL-2010-FORM 3 [12-04-2018(online)].pdf 2018-04-12
29 924-kol-2010-description (provisional).pdf 2011-10-07
29 924-KOL-2010-OTHERS [25-07-2018(online)].pdf 2018-07-25
30 924-KOL-2010-FORM 1-1.1.pdf 2011-10-07
30 924-KOL-2010-FER_SER_REPLY [25-07-2018(online)].pdf 2018-07-25
31 924-kol-2010-form-1.pdf 2011-10-07
31 924-KOL-2010-CLAIMS [25-07-2018(online)].pdf 2018-07-25
32 924-kol-2010-form-2.pdf 2011-10-07
32 924-KOL-2010-FORM 3 [06-10-2018(online)].pdf 2018-10-06
33 924-kol-2010-form-3.pdf 2011-10-07
33 924-KOL-2010-FORM 3 [10-04-2019(online)].pdf 2019-04-10
34 924-kol-2010-gpa.pdf 2011-10-07
34 924-KOL-2010-FORM 3 [10-09-2019(online)].pdf 2019-09-10
35 924-KOL-2010-OTHERS-1.1.pdf 2011-10-07
35 924-KOL-2010-FORM 3 [09-10-2019(online)].pdf 2019-10-09
36 924-KOL-2010-HearingNoticeLetter-(DateOfHearing-14-01-2020).pdf 2019-12-16
36 924-kol-2010-specification.pdf 2011-10-07

Search Strategy

1 PatSeer_25-01-2018.pdf