Claims for Patent: 10,154,856

Summary for Patent: 10,154,856

Title:	Therapeutic substance transfer catheter and method
Abstract:	A cervical transfer catheter (10) for transferring a therapeutic substance to an endocervix or other internal mucosal surfaces of a recipient, the catheter (10) comprising: a catheter body (12) having first and second lumens (14) and (16), the second lumen (16) being adapted, in use, to allow passage and retention of a structure containing the therapeutic substance that will be released slowly and continuously. The catheter (10) also comprises an inflatable balloon (20) provided at a distal end of the first lumen (14), the inflatable balloon (20) being designed to be as small as possible in its inflated condition while still being retained in the uterus by virtue of its shape.
Inventor(s):	Sillender; Mark (Bicton, AU)
Assignee:
Application Number:	14/760,326
Patent Claims:	1. A cervical transfer catheter for transferring a therapeutic substance to an endocervix or other internal mucosal surfaces of a recipient, the catheter comprising: a removable stent containing the therapeutic substance; a catheter body having first and second lumens, the second lumen being adapted, in use, to allow passage and retention of the removable stent, wherein the second lumen is designed to retain the removable stent after the catheter body has been inserted in a recipient's uterus in order to release the therapeutic substance to the endocervix or other internal mucosal surfaces of the recipient; and, an inflatable balloon provided at a distal end of the first lumen, the inflatable balloon being designed to be as small as possible in its inflated condition whilst still being retained in the uterus and endocervix by virtue of its shape so as to retain a portion of the catheter body within the recipient's uterus for a minimum period of several hours, wherein the balloon has a first surface that in use contacts a uterine surface of the recipient, and a second, non-contact surface opposite the first surface, and the second, non-contact surface has a generally concave shape, and wherein the balloon comprises first and second arms, which in the inflated condition extend upwards transversely within the recipient's uterus. 2. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein the stent is a flexible stent. 3. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 2, wherein the stent comprises a hollow outer body made of a permeable polymer or membrane, which is then filled with a liquid, gel or solid material containing the therapeutic sub stance. 4. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 3, wherein the hollow outer body contains a plurality of segments of a material containing the therapeutic substance, each segment being customisable to the particular needs of the recipient. 5. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 2, wherein a portion or the whole of the catheter body is also constructed of a polymer or contains a permeable membrane that allows the passage of the therapeutic substance from the stent into the endocervix or other internal mucosal surfaces of the recipient. 6. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 2, wherein the removable stent containing the therapeutic substance is changed or replaced by exchange of the removable stent. 7. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 4, wherein the removable stent containing the therapeutic substance is replaceable and customisable to allow for dosage variation or multiple combinations of drugs, by using different segments to construct a bespoke structure, or replenishment when medications prove to be satisfactory for the patient and have run out over time. 8. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein the stent has a solid body. 9. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 8, wherein the stent is made of a polymer, or covered by a permeable membrane, that allows for the controlled release of the therapeutic substance. 10. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein the shape of the balloon is adapted in its inflated condition to conform to just a lowest part of the recipient's uterus. 11. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 10, wherein the balloon is shaped to conform to the lowest part of the uterus both transversely and in an anterior-posterior direction. 12. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein the balloon is augmented by inferior protuberances providing extra resistance to expulsion of the catheter. 13. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 12, wherein the protuberances deflate and become flaccid when the balloon is deflated allowing atraumatic removal. 14. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 12, wherein the protuberances enhance a seal of the balloon, when in the inflated condition, to a lower part of the uterus, further blocking expulsion of the catheter. 15. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein a portion of the catheter body located on a vaginal aspect of the cervix is secured by a locking plastic device or an inflatable balloon device that holds the catheter in place and preventing displacement of the catheter. 16. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 15, wherein the locking plastic device or the inflatable balloon device slides up and down the catheter body prior to being secured or inflated so the locking plastic device or the inflatable balloon device lies snugly adjacent to an external aspect of the cervix. 17. A cervical transfer catheter for transferring a therapeutic substance as defined in claim 1, wherein the length of the catheter is such that it limits that portion of its length protruding into a vagina to enhance comfort but still remains accessible in order to allow inflation of the balloon using the first lumen, or passage of a structure containing the therapeutic substance through the second lumen. 18. An improved method of transferring a therapeutic substance to an endocervix or other internal mucosal surfaces of a recipient, the method comprising: providing a catheter body having first and second lumens, the first lumen having an inflatable balloon provided at a distal end of the first lumen; inserting the catheter body into the uterus through the cervix; inflating the balloon with fluid so that the catheter body is retained in the uterus and endocervix; inserting a removable, plastic stent, or inserting a removable, hollow plastic stent containing the therapeutic substance into the second lumen, the stent being lockable in position by a locking mechanism; and, retaining the catheter body in the uterus and endocervix for an extended period of time with the removable stent remaining in the second lumen of the catheter body wherein, in use, the therapeutic substance is released in a controlled manner into the endocervix or other internal mucosal surfaces and thence into the rest of the recipient's body. 19. An improved method of transferring a therapeutic substance as defined in claim 18, wherein the method is used to deliver therapeutic substances to pelvic organs or adjacent structures in other medical applications, including the bladder and urethra, anus and rectum, pelvic floor musculature, pelvic nerves and pelvic blood vessels. 20. An improved method of transferring a therapeutic substance as defined in claim 18, wherein the method is used to deliver therapeutic substances in potential specific applications in the field of obstetrics & gynaecology selected from the group selected from the following: therapeutics to reduce urinary stress incontinence of the bladder, urgency symptoms and urge incontinence affecting the bladder, recurrent urinary tract infections, painful bladder syndrome or interstitial cystitis; therapeutics to provide treatment of inflammatory bowel disease, including corticosteroids, 5-aminosalicyclic acid and it's analogues and derivatives; antispasmodics to reduce the pain associated with some anal conditions, including calcium channel blockers, Dihydropyridine calcium channel blockers, including but not limited to nifedipine, amlodipine, nicardipine, nimodipine; Phenylalkylamine calcium channel blockers including verapamil; Benzothiazepine calcium channel blockers including diltiazem; and non-selective agents including mibefradil, bepridil, fluspirilene, and fendiline; nitric oxide, nitroglycerine, isosorbide mononitrate, nitroprusside and other nitric acid donors; muscular antispasmodics to reduce vaginismus, including drugs that reduce acetylcholine levels comprising trihexyphenidyl hydrochloride, benztropine mesylate, diazepine and the other benzodiazepines, levodopa, reserpine, carbamazepine and their derivatives and analogues; therapeutics to control neuralgic-related pain, including antidepressant medication comprising amitriptyline, imipramine, nortriptyline, duloxetine; and antiseizure medication comprising carbamazepine, gabapentin, lamotrigine, phenytoin, pregabalin, sodium valproate; therapeutics to enhance female sexual response, including sildenafil and other phosphodiesterase type 5 inhibitors, their derivatives and their analogues; analgesics for painful pelvic conditions, including endometriosis, adenomyosis, inflammatory bowel disease, irritable bowel syndrome, chronic pelvic pain, diverticultis, adhesions, painful bladder syndromes, interstitial cystitis, and infections of any structure within the pelvis; oestrogens including oestradiol, oestriol, oestrone and other synthetic oestrogenic derivatives, natural oestrogens including conjugated equine oestrogens, and their derivatives and analogues, to treat vaginal atrophy, dyspareunia, vulval pain and pelvic pain; systemic hormone replacement therapy including oestradiol, oestriol, oestrone and other synthetic oestrogenic derivatives, natural oestrogen, conjugated equine oestrogens, progesterone and other synthetic progestin derivatives, androgens including testosterone, dihydrotestosterone, androstenedione and their derivatives and analogues; and, hormones used to initiate, induce or augment labour, including oxytocin and prostaglandin I.sub.2, prostaglandin E.sub.2 and prostaglandin F.sub.2 alpha and their analogues and derivatives. 21. An improved method of transferring a therapeutic substance as defined in claim 18, wherein the method is used to deliver therapeutic substances in other potential specific applications across the field of medicine selected from the group selected from the following: gastrointestinal medications: antispasmodics including antimuscarinics (atropine sulphate, dicycloverine hydrochloride, propantheline bromide, hyoscine butylbromide), alverine citrate, mebeverine hydrochloride; motility stimulants including metoclopramide, domperidone, anti-secretory drugs including cimetidine, famotidine, nizatidine, ranitidine; proton pump inhibitors including esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole; antimotility drugs including co-phenotrope, loperamide hydrochloride; anti-inflammatory bowel disease medications including balsalazide sodium, mesalazine, olsalazine sodium, sulfasalazine; corticosteroids including beclometasone dipropionate, budesonide, hydrocortisone, prednisolone; immune response modifiers including azathioprine, ciclosporin, mercaptopurine, methotrexate, laxatives including methylnaltrexone bromide, prucalopride; glyceryl trinitrate for anal fissures, Ursodeoxycholic ursodeoxycholic acid for prevention of gallstones; medications used in the field of cardiology: cardiac inotropes including digoxin, enoximone, and milrinone; diuretics including thiazides (bendroflumethiazide, chlortalidone, cyclopenthiazide, indapamide, metolazone, xipamide), loops (bumetanide, furosemide, torasemide), potassium sparing agents (amiloride hydrochloride, triamterene), and aldosterone antagonists (spironolactone, eplerenone); anti-arrhythmic drugs including dronedarone, digoxin, verapamil, amiodarone hydrochoride, disopyramide, flecainide acetate, procainamide, propafenone hydrocholride, and beta-blockers (propranolol hydrochloride, acebutolol, atenolol, bisoprolol fumarate, carvedilol, celiprolol hydrochloride, esmolol hydrochloride, labetolol hydrochloride, metoprolol tartrate, nadolol, nebivolol, oxprenolol hydrochloride, pindolol, sotalol hydrochloride, timolol maleate), ivabradine, ranolazine; other medications including anti-hypertensive drugs including hydralazine hydrochloride, prazosin, doxazosin, indoramin, terazosin, sildenafil, methyldopa, clonidine hydrochloride, and moxonidine; drugs used in heart failure or hypertension including captopril, cilazapril, enalapril maleate, fosinopril sodium, imidapril hydrochloride, lisinopril, moexipril hydrochloride, perindopril erbumine, perindopril arginine, quinapril, rampiril, trandolapril, candesartan cilexetil, erposartan, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, valsartan, and aliskiren, vasodilators include glyceryl trinitrate, isosorbide dinitrate, isosorbide mononitrate, amlodipine, diltiazem hydrochloride, felodipine, isradipine, lacidipine, lercanidipine hydrochloride, nicardipine hydrochloride, nifedipine, nimodipine, verapamil hydrochloride, nicorandil, cilostazol, inositol nicotinate, moxisylyte, naftidrofuryl oxalate, and pentoxifylline; further medications including anticoagulants comprising heparin, dalteparin sodium, enoxaparin sodium, tinzaparin sodium, danaparoid sodium, bivalirudin, lepirudin, fondaparinux sodium, warfarin sodium, acenocoumarol, phenindione, dabigatran etexilate, apixaban, and rivaroxaban; antiplatelet drugs including aspirin, clopidogrel, dipyridamole, prasugrel, and ticagrelor; lipid regulating drugs including atorvastatin, fluvastatin, pravastatin sodium, rosuvastatin, simvastatin, ezetimibe, bezafibrate, ciprofibrate, fenofibrate, gemfibrozil, acipimox, and nicotinic acid; respiratory medications comprising: drugs affecting the airways including bambuterol hydrochloride, formoterol fumarate, indacaterol, salbutamol, salmeterol, terbutaline sulphate, ephedrine hydrochloride, ipratropium bromide, tiotropium, theophylline, aminophylline, beclomethasone dipropionate, budesonide, ciclesonide, fluticasone propionate, mometasone furoate, sodium cromoglicate, nedocromil sodium, montelukast, and zafirlukast, roflumilast; antihistamines including acrivastine, bilastine, cetirizine hydrochloride, desloratadine, fexofenadine hydrochloride, levocetirizine hydrochloride, loratadine, mizolastine, rupatadine, alimemazine tartrate, chlorphenamine maleate, clemastine, cyproheptadine hydrochloride, hydroxyzine hydrochloride, ketotifen, and promethazine hydrochloride; drugs having a central nervous system effect comprising: anti-anxiety medication including nitrazepam, flurazepam, loprazolam, lormetazepam, temazepam, zaleplon, zolpidem tartrate, zopiclone, chloral hydrate, clomethiazole, sodium oxybate, diazepam, alprazolam, chlordiazepoxide hydrochloride, lorazepam, and oxazepam; anti-psychotic medication including benperidol, chlorpromazine hydrochloride, flupentixol, haloperidol, levomepromazine, pericyazine, perphenazine, pimozide, prochlorperazine, promazine hydrochloride, sulpiride, trifluoperazine, zuclopenthixol, zuclopenthixol actetate, amisulpride, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, flupentixol decanoate, fluphenazine decanoate, olanzapine embonate, pipotiazine palmitate, and zuclopenthixol decanoate; further medications including antimanic drugs including asenapine, carbamazepine, valproic acid, lithium carbonate, and lithium citrate; antidepressant drugs including amitriptyline hydrochloride, clomipramine hydrochloride, dosulepin hydrochloride, doxepin, imipramine hydrochloride, lofepramine, nortriptyline, trimipramine, mianserin hydrochloride, trazodone hydrochloride, phenelzine, isocarboxazid, tranylcypromine, moclobemide, citalopram, escitalopram, fluoxetine, fluvoxamine maleate, paroxetine, sertraline, agomelatine, duloxetine, mirtazapine, reboxetine, tryptophan, venlafaxine; antinausea medication includes cinnarizine, cyclizine, promethazine hydrochloride, promethazine teoclate, droperidol, domperidone, metoclopramide hydrochloride, granisetron, ondansetron, palonosetron, aprepitant, fosaprepitant, nabilone, hyoscine hydrobromide, and betahistine dihydrochloride; analgesic medications including aspirin, paracetamol, nefopam hydrochloride, buprenorphine, codeine phosphate, diamorphine hydrochloride, dihydrocodeine tartrate, dipipanone hydrochloride, fentanyl, hydromorphone hydrochloride, meptazinol, methadone hydrochloride, morphine salts, oxycodone hydrochloride, papaveretum, pentazocine, pethidine hydrochloride, tapentadol, and tramadol hydrochloride; antimaigraine medication includes pizotifen, and clonidine hydrochloride; antiepileptic medications including carbamazepine, eslicarbazepine acetate, oxcarbazepine, ethosuximide, gabapentin, pregabalin, lacosamide, lamotrigine, levetiracetam, phenobarbital, pimidone, phenytoin, retigabine, rufinamide, tiagabine, topiramate, sodium valproate, vigabactrin, zonisamide, clobazam, and clonazepam; antiparkinsonian medication including apomorphine hydrochloride, bromocriptine, cabergoline, pergolide, pramipexole, ropinirole, rotigotine, levodopa, co-beneldopa, co-careldopa, rasagiline, selegiline hydrochloride, entacapone, tolcapone, amantadine hydrochloride, orphenadrine hydrochloride, procyclidine hydrochloride, and trihexyphenidyl hydrochloride; drugs used in the treatment of substance dependence including acamprosate calcium, disulfiriam, naltrexone, bupropion hydrochloride, nicotine, varenicline, buprenorphine, methadone hydrochloride, and naltrexone hydrochloride; dementia medication including donepezil, galantamine, memantine hydrochloride, and rivastigmine; medications used in the management of endocrine conditions including: insulins including intermediate-acting and long-acting preparations; antidiabetic drugs including glibenclamide, gliclazide, glimepiride, glipizide, tolbutamide, metformin, acarbose, exenatide, linagliptin, liraglutide, nateglinide, pioglitazone, repaglinide, saxagliptin, sitagliptin, and vildagliptin, thyroxines including levothyroxine sodium, liothyronine sodium, and armour thyroid; antithyroid drugs include carbimazole and propylthiouracil, steroids including fludrocortisone acetate, betamethasone, deflazacort, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone; female sex hormones including oestrogens (conjugated equine oestrogens, oestradiol, oestradiol valerate, ethinyloestradiol, oestriol, mestranol and their analogues and derivatives), tibolone, raloxifene hydrochloride, progestogens (progesterone, dydrogesterone, medroxyprogesterone acetate, megestrol acetate, levonorgestrel, dienogest, norethisterone, norethisterone acetate, norgestrel, desogestrel, norgestimate, gestodene, drospirenone, etynodiol diacetate and their analogues and derivatives), and testosterone esters (enantate, propionate, deconoate, undecanoate, phenylpropionate, isocaproate), dehydroepiandrosterone and mesterolone; also selective progestogen-receptor modulators including ulipristal acetate and other members of the same family; also chorionic gonadotrophin, choriogonadotropin alfa, corifollitropin alfa, follitropin alfa and beta, human menopausal gonadotrophins, lutropin alfa, gonadorelin; other hormones including somatropin, human growth hormone, desmopressin, vasopressin, tolvaptan; hormone antagonists including anastrozole, exemestane, fulvestrant, letrozole, tamoxifen, and toremifene; drugs affecting bone metabolism including calcitonin, parathyroid hormone, teriparatide, bisphosphonates (alendronic acid, disodium etidronate, disodium pamidronate, ibandronic acid, risedronate sodium, sodium condronate, zoledronic acid, denosumab, and strontium ranelate; other endocrine drugs including bromocriptine, cabergoline, quinagolide, cetrorelix, danazol, ganirelix, buserelin, goserelin, histrelin, leuprorelin acetate, nafarelin, and triptorelin; medications used for treating infections including the following antibiotics: penicillins (benzylpenicillin sodium, phenoxymethylpenicillin, flucoxacillin, temocillin, amoxicillin, ampicillin, co-amoxiclav, co-fluampicil, piperacillin, tazobactam, ticarcillin with clavulanic acid, and pivmecillinam hydrochloride; cephalosporins, carbapenems and other beta-lactams (cefaclor, cefadroxil, cephalexin, cefixime, cefotaxime, cefpodoxime, cefradine, ceftazidime, ceftriaxone, cefuroxime, doripenem, ertapenem, imipenem with cilastatin, meropenem, and aztreonam); tetracycline, demecolcycline hydrochloride, doxycycline, lymecycline, minocycline, oxytetracycline, and tigecycline; aminoglycosides (gentamicin, amikacin, tobramycin), macrolides (azithromycin, clarithromycin, erythromycin, and telithromycin), other antibiotics include clindamycin, chloramphenicol, sodium fusidate, vancomycin, teicoplanin, daptomycin, linezolid, colistimethate sodium, co-trimoxazole, sulfadiazine, trimethoprim, metronidazole, tinidazole, ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, nitrofurantoin, and methenamine hippurate; medications for treating other infections including: antifungals comprising fluconazole and itraconazole; antivirals including abacavir, didanosine, emtricitabine, lamivudine, tenofovir disoproxil, zidovudine, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, nelfinavir, saquinavir, tipranavir, efavirenz, etravirine, nevirapine, enfuvirtide, maraviroc, raltegravir, acyclovir, famciclovir, inosine pranobex, valaciclovir, adefovir dipivoxil, entecavir, telbivudine, boceprevir, and telaprevir; antimalarials including artemether with lumefantrine, chloroquine, mefloquine, primaquine, proguanil hydrochloride, atovaquone, pyrimethamine, sulfadoxine, and quinine; anti TB drugs including capreomycin, cycloserine, ethambutol hydrochloride, isoniazid, pyrazinamide, rifabutin, rifampicin, and streptomycin; other medications which are used in obstetrics and gynaecology including carbetocin, carboprost, dinoprostone, ergometrine maleate, gemeprost, oxytocin, mifepristone, atosiban, salbutamol, and terbutaline; antifungals including clotrimazole, miconazole, econazole, fenticonazole; drugs used for restoring the vaginal environment including clindamycin, metronidazole, and lactic acid; contraceptives including combined contraception and progestogen-only contraception; using combinations and/or varying amounts of the female sex hormones noted above; varying combinations of the female sex hormones listed above for hormone replacement therapy; drugs for urinary dysfunction including darifenacin, duloxetine, fesoterodine fumarate, flavoxate hydrochloride, oxybutynin hydrochloride, propantheline bromide, propiverine hydrochloride, solifenacin succinate, tolterodine tartrate, trospium chloride, alfuzosin hydrochloride, doxazosin, indoramin, prazosin, tamsulosin hydrochloride, terazosin, bethanechol chloride, and distigmine bromide; drugs used to aid sexual response including sildenafil, tadalafil, and vardenafil; other medications including interferon alfa, peginterferon alfa, interferon beta, interferon gamma-1b, and immunosuppressants including ciclosporin, tacrolimus, and sirolimus; and, drugs that are used in musculoskeletal & joint disease, including ibuprofen, naproxen, fenoprofen, flurbiprofen, dexketoprofen, ketoprofen, tiaprofenic acid, diclofenac sodium, diclofenac potassium, aceclofenac, etodolac, acemetacin, indomethacin, mefanamic acid, meloxicam, nabumetone, piroxicam, sulindac, tenoxicam, tolfenamic acid, ketorolac, parecoxib, etoricoxib, celecoxib, and other NSAIDs & Cox-2 inhibitors; aspirin; sodium aurothiomalate, penicillamine, chloroquine, hydroxychloroquine sulphate, allopurinol, febuxostat, probenecid, sulfinpyrazone, glucosamine, baclofen, cannabis extract, dantrolene sodium, diazepam, tizanidine, and quinine. 22. A cervical transfer catheter system that transfers a therapeutic substance to a recipient, the cervical transfer catheter system comprising: a removable stent containing the therapeutic substance; a catheter body having first and second lumens, the catheter body is positionable in an endocervix of the recipient, the second lumen is designed to retain the removable stent after the catheter body has been inserted in a recipient's uterus; an inflatable balloon provided at a distal end of the first lumen, wherein when the catheter body is positioned in the endocervix the inflatable balloon is positioned in a uterus of the recipient so as to retain a portion of the catheter body within the recipient's uterus for a minimum period of several hours; wherein the balloon comprises first and second arms, which in the inflated condition extend upwards transversely within the recipient's uterus, so that in a side view the inflatable balloon has a V-shape when inflated with an external surface that is convex and that in use contacts a surface of the uterus, and an internal surface opposite the external surface, and the internal surface is generally concave.

Details for Patent 10,154,856

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	June 23, 1987	10,154,856	2033-02-06
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	October 16, 1986	10,154,856	2033-02-06
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	February 04, 1999	10,154,856	2033-02-06
Emd Serono, Inc.	SAIZEN	somatropin	For Injection	019764	October 08, 1996	10,154,856	2033-02-06
Emd Serono, Inc.	SAIZEN	somatropin	For Injection	019764	August 29, 2000	10,154,856	2033-02-06
Emd Serono, Inc.	SAIZEN	somatropin	For Injection	019764	January 16, 2007	10,154,856	2033-02-06
Ferring Pharmaceuticals Inc.	ZOMACTON	somatropin	For Injection	019774	May 25, 1995	10,154,856	2033-02-06