PATENTS ACT t970 SECTION 15 DECISION

Transcription

1 PATENTS ACT t970 SECTION 15 IN THE MATTER OF AN APPLICATION FOR PATENT, NUMBER I752/CIJW2OO6 FILED ON 25th SEPTE,MBER M / s. GLYCOSCIENCE LABORATORIES, INC, JAPAN... The Applicants. HEARING HELD ON 23'd JULY.2OO9 Present: Ms. Vaishnavi S K of DePenning & DePenning, Agent for the Applicants. Mr. R. Rajini, Examiner of Patents & Designs DECISION An application for Patent for an invention titled "PHARMACEUTICAL AGENT CONTAINING HYALURONAN AS AN ACTIVE INGREDIENT', WAS fi Ed by M / s. DePenning & DePenning on behalf of M / s. GLYCOSCIENCE LABORATORIES, INC, JAPAN and the same was allotted convention Appfication Number. 1752!CHE12OO6 dated 25th September The applicants have also claimed priority from Japanese patent applications identified as dated 26th September 2005, dated 12th October 2005 and dated 01't December 2005.

2 The complete specification of the instant application at the time of filing had claims as follows: 1' A therapeutic or prophyractic agent for an inframmation and a neural dysfunction, comprising hyaruronan as an active ingredient. 2' The therapeutic or prophylactic agent according to Claim 1, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a singre unit being _D_ glucuronic acid- p -1,3-D_N_acetylglucosamine_ 13 _1,4_. 3. The therapeutic or inflammation and the prophylactic agent according to craim 1, wherein the neural dysfunction is due to an autoimmune disease. 4' The therapeutic or prophylactic agent according to Claim 1, wherein the inflammation and the neurar dysfunction is due to a neurar disease. 5' The therapeutic or prophylactic agent according to Claim 1, wherein the inflammation and the neurar dysfunction is due to spinar cord injury. 6. The therapeutic or prophylactic agentaccording to Claim 1, wherein the inflammation and the neural dysfunctionis due to asthma. 7. The therapeutic or prophylactic agent according to claim 1, wherein the inflammation and the neural dysfunction is due to a murtiple sclerosis. 8' A method for treating or preventing an inflammation comprising a step of administering an effective amount of hyaluronan to a subject in need of a treatment.

3 g. The method for treating or preventing an autoimmune disease according to Claim 8, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -D-glucuronic acid-b -1,3-D-N-acetylglucosamine-B -1, The method for treating or preventing an autoimmune disease according to Claim B, wherein the inflammation and the neural dysfunction is due to an autoimmune disease. 11. The method for treating or preventing an autoimmune disease according to Claim 8, wherein the inflammation and the neural dysfunction is due to a neural disease. 12. The method for treating or preventing an autoimmune disease according to Claim B, wherein the inflammation and the neural dysfunction is due to a spinal cord injury. 13. The method for treating or preventing an autoimmune disease according to Claim 8, wherein the inflammation and the neural dysfunction is due to asthma. 14. The method for treating or preventing an autoimmune disease according to Claim 8, wherein the inflammation and the neural dysfunction is due to a multiple sclerosis. 15. A cytokine-associated gene expression inhibitor comprising hyaluronan as an active ingredient. 16. The cytokine-associated gene expression inhibitor according to Claim 15, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -D-glucuronic acid-b -1,3-D-N-acetylglucosamine-B -1,4-'

4 17. The cytokine-associated gene expression inhibitor according to Claim15, wherein said cytokine-associated gene is a gene associated with an inflammatory cytokine. 18' The cytokine-associated gene expression inhibitor according to Claim15 which is an injection formulation and an oral formulation. 19' A chemokine-associated gene expression inhibitor comprising hyaluronan as an active ingredient. 20' The chemokine-associated gene expression inhibitor according to Claim 1g, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -D-glucuronic acid-b -1,3-D-N-acetylglucosamine_B _1,4_. 21. The chemokine-associated gene expression inhibitor according to Claim 1g, which is an injection formulation and an oral formulation. 22' A cell viability enhancer comprising hyaluronan as an active ingredient. 23' The cell viability enhancer according to Claim 22, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -D-glucuronic acid-b -1,3-D-N-acetylglucosamine-B -1, fhe cell viability enhancer according to Claim 23 which is an oral formulation. 25. A synaptic transmission promoter, comprising hyaluronan as an active ingredient. 26' The synaptic transmission promoter according to Claim 25, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -Dglucuronic acid-b -1,3-D-N-acetylglucosamine-B -1,4-.

5 27.The synaptic transmission promoter according to Claim 25 which is an intraduralformulation, a subcutaneous formulation, an intravenous formulation or an oralformulation. 28. A synaptic protector comprising hyaluronan as an active ingredient. 29. The synaptic protector according to Claim 28, wherein said hyaluronan is a tetrasaccharide containing 2 units, with a single unit being -D-glucuronic acid-b - 1,3-D-N-acetylglucosamine-B -1, The synaptic protector according to Claim 28 which is an intradural formulation, a subcutaneous formulation, an intravenous formulation, intranasal or an oral formulation. The request for examination was filed by the agent on 25'n September 2006 and the same was examined under the provision of section 12 of the patents Act, The First Examination Report was issued to the agent on 07th July 2008 which inter-alia included objections lack of novelty, inventive step, and under section 3(d), (i) and (e). The agents submitted their reply to the First Examination Report on 19th June 2009 wherein they amended the claims as, 1. A medicament for intraspinal administration for the treatment of an inflammation due to a multiple sclerosis or a neural dysfunction due to a multiple sclerosis comprising a tetrasaccharide containing 2 units, with a single unit being D-glucuronic acid-b-1,3-d-n-acetylglucosamine-b-1,4-' for the manufacture of a medicament.

6 The medicament as claimed in patient. The medicament as claimed in administration once a day. The medicament as claimed in any preceding claims, wherein it is an injection formulation containing a ph modifier, an osmotic agent and distilled water for injection. The medicament as claimed in claim 4, wherein the ph modifier is selected from the group consisting of hydrochloric acid, sodium hydroxide, lactic acid, sodium lactate, sodium monohydrogen phosphate and sodium dihydrogen phosphate" The medicament as claimed in claims 4 or 5, wherein the osmotic agent is sodium chloride or glucose. The medicament as claimed in any of claims 4 to 6, wherein the injection formulation is supplemented also with mannitol, dextrin, cyclodextrin or gelatin. 8. The medicament as claimed in any of claims 1 to 3, wherein the medicament is an emulsion for injection containing an emulsifier and water. 9. The medicament as claimed in claim 8, wherein the emulsifier is selected from the group consisting of lecithin, polysorbate 80, and polyethylene hydrogenated castor oil. claim 1, wherein it contains the tetrasaccharide in a dosage of from0.05 to 50 mg/kg body weight of the claims 1 or 2, wherein it is for The agents also requested for an opportunity of being heard before any decision adverse to the applicant is taken. As requested by the agents, a hearing was offered and held on 23'd July During the hearing, the agent for the applicants submitted that "in CA (D1), nerve damage due to spinal cord'injury'disclosed D1, and a neural dysfunction due to 'disease' such as multiple sclerosis, which is disclosed

7 in the present specification, are different in their pathophysiologies. D1 discloses well-known examples of neural dysfunction including multiple sclerosis; however, their pathogenic mechanisms are completely different. The description of D1 is incorrect with no scientific basis. The differences between multiple sclerosis and traumatic spinal cord injury are as follows: Multiple sclerosis Traumatic spinal co Category Autoimmune disease Traumatic iniu IFN-beta effective ineffective T-cell invasion + Animal models EAE model Injury Regarding the category of disease, multiple sclerosis is classified as an autoimmune disease and traumatic spinal cord injury is classified as trauma. The immune-mediated pathology as seen in multiple sclerosis is not typical for traumatic spinal cord injury. Regarding the effective treatment, INF-beta is commonly used for the treatment of multiple sclerosis, whereas INF-beta is ineffective for traumatic spinal cord injury. Regarding T-cell invasion, the most common form of multiple sclerosis is what is known as relapsing-remitting, and myelinated axons are destroyed as consequence of T-cell invasion in relapsing phase. On the other hand, traumatic spinal cord injury shows neither T cell invasion nor demyelination. Regarding animal models, experimental allergic encephalomyelitis (EAE) is widely used as a model of multiple sclerosis, which is induced by stimulating T- cell mediated immunity to myelin proteins via immunization with myelin antigens. On the other hand, crushing the spinal cord using tweezers produces traumatic injury. Only the therapeutic efficacy of intradural administration of HA for traumatic spinal cord injury is supported with the working examples of D1, and

8 D1 neither discloses nor suggests the therapeutic efficacy of HA4 for autoimmune disease such as multiple sclerosis. D1 does not disclose the mechanism of action of HA4 in the treatment of traumatic spinal cord injury. However, this efficacy may be due to promotion of the heat shock protein expression and inhibition of apoptosis. None of the references disclose the therapeutic efficacy of intraspinal administration of HA4 for multiple sclerosis. Only DG discloses the therapeutic efficacy of HA for multiple sclerosis. However, the pharmaceutical composition of D6 comprises a high-molecular-weight Zn-HA complex, which is a different kind of compound from HA without Zn. HA4 is more effective than high-molecularweight HA. Further, the therapeutic efficacy of HA4 for multiple sclerosis is unforeseen and is remarkable. None of the references disclose the therapeutic efficacy of intraspinal administration of HA4 for multiple sclerosis. The claimed medicament is as such novel and inventive". Therefore, they requested to reconsider the objection favorably and allow the application to proceed to grant. follows, After hearing all the arguments, it was explained to the agent as Claims do not involve inventive step under section 2(1)( ja ) of the patents Act Principal claim is directed to "A medicament for intraspinal administration for the treatment of an inflammation due to a multiple sclerosis or a neural dysfunction due to a multiple sclerosis comprising a tetrasaccharide containing 2 units, with a single unit being D-glucuronic acid-b-1,3-d-n_ acetylglucosamine-b-1,4-, for the manufacture of a medicament". Though the claim is directed to medicament the one and the only active ingredient is HA4 (tetarasaccharide containing 2 units, with a single unit being D-glucuronic acid-b- 1, 3-D-N-acetylglucosamine-B-1, 4-,).tnjection formulation of the medicament

9 is a conventional formulation. Excipients used in the formulation are inactive substances used as a carrier for the active ingredients of a medication' Activity of the medicament is only due to the presence of the active ingredient i'e'' HA4' Therefore claims relate to mere application / use' compound HA4 is well known from prior art. For example ca (family memberof wo ) and JP , were cited in the First Examination Report itself. The same has been accepted by the instant application. ln page 3 of the instant specification, it is given that "HA4 was reported to have therapeutic and inhibitory effect in an organ preservation' hepatic disorder and gastric ulcer (see, wo 2oo )' HA4 is also known to have a stress protein expression enhancing effect and a cell death inhibiting effect... In addition, HA4 is known to be effective therapeutically in a spinal cord injured model (see, " ' HA4 i.e., tetrasaccharide is well known from ca ' In page 5 it is given thatlhe glycoside bond between GtcA and GlcNAc is preferably a F 1-3 bond, and the glycosidic bond between GlcNAc and GlcA is preferabty F 1-4 bond'. In page 1 it is given that GlcA is glucuronic acid and GlcNAc is N- acety g ucosamine. npagel0firstparagraphitisgiventhatlow molecular-weight saccharide composed of at least GlcA and/or G[cNAc or a pharmaceutically acceptable salt thereof may be 100 micro g to 1000 mg per adult per administration. ln page 7 last paragraph it is given that 'the administration method of the therapeutic agent of the present invention is not particularly limited as long as the therapeutic agent of the present invention can exert an effect on nerve damage. Examples of administration routes include injection (intradural, intravenous, intramuscular, subcutaneous' intraculataneous, intraperitoneal, or the likel, transnasal' oral' percutaneous, and inhalation. The administration method such as direct administration by injection to a certain site or drip administration is appropriately selected depending on a disease or a site to be applied' ln the case of intradural administration or the like, an implantable pump for drug infusion may be

10 implanted in the body to per{orm continuous administration'. In page B it is given that'the liquid formulation may be produced by dissolving a low molecular-weight saccharide composed of at least GlcA and/or GlcNAc or a pharmaceutically acceptable salt thereof, for example, an appropriate aqueous solvent or a solvent commonly used for drugs. Example of such solvents include distilled water, buffers, physiological saline and water containing a water-miscible organic solvent or the like'. ln the case that the therapeutic agent of the present invention is provided as an injectable agent, its form may be a solution, frozen product, or freeze-dried product. The therapeutic agent is filled and sealed in an appropriate container such as an ampule, vial or syringe for injection, for distribution or preservation, and it may be administered as an iniection. For formulating the therapeutic agent of the present invention, a known method may be used. When the treatment agent is formulated, other active ingredients (such as anti-inflammatory drugs, analgesics, vitamin preparations, antibacterial agents, growth factors and adhesion factors), or ingredients generally used in medicines such as conventional stabilizing agents, emulsifiers, osmotic regutators, ph regulators, buffers, tonicity agents, preservatives, soothing agents, colorants, diluents, binders, lubricants and disintegrators may be used, as long as those ingredients exert no unfavorable influence on the above described saccharide or a pharmaceutically acceptable salt thereof and exert no influence on the effects of the present invention'. In page 1 paragraph 2, it is given that JP discloses an aqueous solution containing hyaluronic acid (HA) or a pharmaceutically acceptable salt thereof for spinal cord perfusion, and it describes that the solution for perfusion may be used in the spinal cord perfusion therapy for spinal cord injury...'. In page 9 paragraph 2 it is given that "the'condition where a treatment for nerve damage is desired' is not particularly limited, but examples thereof include spinal cord injury or nerve trauma such as head trauma, cerebral (infantile) paralysis, spinal vascular damage, cervical spondylosis, senile dementia, Alzheimer's disease, Parkinson's disease, and spinocerebellar degeneration (hereditary spastic paraparesis). Of these' the treatment agent is preferably applied to spinal cord injury include traumatic spinal l0

11 cord injury, vertebral degenerative disease (spondylosis or the like), vetevral inflammatory disease (spondylitis, chronic rheumatoid arthritis or the like), tumor (spinal corci tumor, vertebral tumor or the like), vascular disease (spinal cord bleeding, cerebral embolism, spinal paralysis caused by extramedullary vascular damage or the like), myelitis (arachnoiditis, viral myelitis bacterial myelitis, or the like), multiple sclerosis, and amyotrophic lateral sclerosis. In particular, the therapeutic agent is effective for traumatic spinal cord injury". EP discloses the claimed hyaluronic acids as being Hsp expression promoting agents responsible for the inhibition of cell death, cell injury, tissue protection ll- 10 production promoter and ll-8 production inhibitor. JP discloses hyaluronic acids as being stress protein expression enhancer, cell lesion suppressor and cell death suppressor. WO and US disclose hyaluronic acid as being inhibitors of T-cells. WO disclose pharmaceutical composition comprising a Zinc-hyaluronate complex for the treatment of multiple sclerosis" From the above discussion it is clear that the compound HA4, its therapeutic activity, quantity for administration, administration routes, injection formulation, use in spinal cord perfusion therapy, use in spinal cord injury, use for nerve damage and use for multiple sclerosis are known. From the above disclosure, it is obvious to the person skilled in the art to use the same known compound for the same known use for multiple sclerosis or neural dysfunction by varying the quantity and administering by different route such as intraspinal administration. Therefore, claims do not constitute an invention under section 2(1)( j ) of the Patents Act In connection with the above argument, claims relate to new use for a known compound therefore fall within the scope of section 3(d) of the Patents Act {Section 3 (d): the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known l1

12 substance or of the mere use of a known process, machine or apparatus unlessuch known process results in a new product or employs at least one new reactant. Explanation: For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy;). From the above disclosure it is clear that the compound HA4, its therapeutic activity, quantity for administration, administration routes, injection formulation, use in spinal cord perfusion therapy, use in spinal cord injury, use for nerve damage and use for multiple sclerosis are known from the prior art" Medicament for intraspinal administration for the treatment of an inflammation due to a multiple sclerosis or a neural dysfunction due to a multiple sclerosis of instant application is a new use for known compound, which fall within the scope of section 3(d) of the Patents Act 1970, therefore cannot be allowed. ln the seven examples given in the specification, not even a single injection formulation has been disclosed as claimed in the instant application. The examples must contain the actual medicament formulation with exact ratio/weight o/o of the excipients for which the test has been carried out. The invention and its operation or use and the method by which it is to be performed are not fully and particularly described in the complete specification. The complete specification should disclose the best method of performing the invention, which is known to the applicant and for which he is entitled to claim protection. Also claims do not sufficiently define the invention for which protection is claimed. Claims relate to mere application/use. The presently claimed medicament does not disclose any injection formulation explicitly with the ratio/weight % of the excipients. Therefore the complete specification do not t2

13 1970. requirementsunder section 10 (4) (a), (b) and (c) of the Patents Act ln connection with the above arguments, claims are not fairly based on the matter discrosed in the specification. And therefore do not meet the requirements under section 10 (5) of the Patents Act 1970' Therefore, l refuse to proceed with this application for Patent, No' 1752 CHE 2O06 u nder section15 of the Patents Act, Dated this 06th day of August 2009' (8. AHILAN) Assistant Controtler of Patents & Designs Copy to: DePenning and DePenning' 31 South Bank Road, Chennai ' IJ