PTO Form 1478 (Rev 9/2006)
`
`OMB No. 0651-0009 (Exp 09/30/2008)
`
`Trademark/Service Mark Application, Principal Register
`
`Serial Number: 77118853
`Filing Date: 02/28/2007
`
`The table below presents the data as entered.
`
`Input Field
`
`Entered
`
`SERIAL NUMBER
`
`MARK INFORMATION
`
`*MARK
`
`SPECIAL FORM
`
`USPTO-GENERATED IMAGE
`
`LITERAL ELEMENT
`
`COLOR MARK
`
`DESCRIPTION OF THE MARK
`(and Color Location, if applicable)
`
`PIXEL COUNT ACCEPTABLE
`
`PIXEL COUNT
`
`APPLICANT INFORMATION
`
`*OWNER OF MARK
`
`*STREET
`
`*CITY
`
`*STATE
`(Required for U.S. applicants)
`
`*COUNTRY
`
`*ZIP/POSTAL CODE
`(Required for U.S. applicants only)
`
`LEGAL ENTITY INFORMATION
`
`*TYPE
`
`*STATE/COUNTRY OF INCORPORATION
`
`GOODS AND/OR SERVICES SECTION
`
`77118853
`
`\\TICRS2\EXPORT12\771\188 \77118853\xml1\APP0002.JP
`G
`
`YES
`
`NO
`
`MYOZYME
`
`NO
`
`The mark consists of the word MYOZYME and the depiction
`of a person.
`
`YES
`
`940 x 265
`
`Genzyme Corporation
`
`500 Kendall Square
`
`Cambridge
`
`Massachusetts
`
`United States
`
`01701
`
`CORPORATION
`
`Massachusetts
`
`INTERNATIONAL CLASS
`
`005
`
`DESCRIPTION
`
`FILING BASIS
`
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)FIRST USE ANYWHERE DATE
`
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)FIRST USE IN COMMERCE DATE
`
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)SPECIMEN
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)FILE NAME(S)
`
`Pharmaceuticlas for use in the treatment of lysosomal storeage
`diseases
`
`SECTION 1(a)
`
`At least as early as 06/30/2006
`
`At least as early as 06/30/2006
`
`\\TICRS2\EXPORT12\771\188 \77118853\xml1\APP0003.JP
`G
`
`

`
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)SPECIMEN DESCRIPTION
`
`ATTORNEY INFORMATION
`
`NAME
`
`ATTORNEY DOCKET NUMBER
`
`FIRM NAME
`
`STREET
`
`CITY
`
`STATE
`
`COUNTRY
`
`ZIP/POSTAL CODE
`
`PHONE
`
`FAX
`
`EMAIL ADDRESS
`
`package insert included with product
`
`Lawrence R. Robins
`
`08727.0038-00000
`
`Finnegan, Henderson, Farabow, Garrett & Dunner L.L.P.
`
`901 New York Avenue, N.W.
`
`Washington
`
`District of Columbia
`
`United States
`
`20001
`
`202-408-4000
`
`202-408-4400
`
`docketing@finnegan.com
`
`AUTHORIZED TO COMMUNICATE VIA EMAIL
`
`Yes
`
`CORRESPONDENCE INFORMATION
`
`NAME
`
`FIRM NAME
`
`STREET
`
`CITY
`
`STATE
`
`COUNTRY
`
`ZIP/POSTAL CODE
`
`PHONE
`
`FAX
`
`EMAIL ADDRESS
`
`AUTHORIZED TO COMMUNICATE VIA EMAIL
`
`FEE INFORMATION
`
`NUMBER OF CLASSES
`
`FEE PER CLASS
`
`TOTAL FEE DUE
`
`SIGNATURE INFORMATION
`
`SIGNATURE
`
`SIGNATORY'S NAME
`
`SIGNATORY'S POSITION
`
`DATE SIGNED
`
`FILING INFORMATION SECTION
`
`Lawrence R. Robins
`
`Finnegan, Henderson, Farabow, Garrett & Dunner L.L.P.
`
`901 New York Avenue, N.W.
`
`Washington
`
`District of Columbia
`
`United States
`
`20001
`
`202-408-4000
`
`202-408-4400
`
`docketing@finnegan.com
`
`Yes
`
`1
`
`325
`
`325
`
`/Lawrence R. Robins/
`
`Lawrence R. Robins
`
`Attorney for Applicant
`
`02/28/2007
`
`SUBMIT DATE
`
`Wed Feb 28 17:37:05 EST 2007
`
`

`
`TEAS STAMP
`
`USPTO/BAS-XX.XXX.X.X-2007
`0228173705121135-77118853
`-36091ce41d75af78e9d1b20f
`ccf17a12d-CC-778-20070228
`173205945077
`
`

`
`PTO Form 1478 (Rev 9/2006)
`
`OMB No. 0651-0009 (Exp 09/30/2008)
`
`Trademark/Service Mark Application, Principal Register
`
`Serial Number: 77118853
`Filing Date: 02/28/2007
`
`To the Commissioner for Trademarks:
`
`MARK:(cid:160)MYOZYME(cid:160)(stylized and/or with design, see mark)
`
`The literal element of the mark consists of MYOZYME. The applicant is not claiming color as a feature of the mark. The mark consists of the
`word MYOZYME and the depiction of a person.
`The applicant, Genzyme Corporation, a corporation of Massachusetts, having an address of 500 Kendall Square, Cambridge, Massachusetts,
`United States, 01701, requests registration of the trademark/service mark identified above in the United States Patent and Trademark Office on
`the Principal Register established by the Act of July 5, 1946 (15 U.S.C. Section 1051 et seq.), as amended.
`
`(cid:160)(cid:160)(cid:160)(cid:160)(cid:160)(cid:160) International Class 005: (cid:160)Pharmaceuticlas for use in the treatment of lysosomal storeage diseases
`
`Use in Commerce: The applicant is using the mark in commerce, or the applicant's related company or licensee is using the mark in commerce, or
`the applicant's predecessor in interest used the mark in commerce, on or in connection with the identified goods and/or services. 15 U.S.C.
`Section 1051(a), as amended.
`
`In International Class 005, the mark was first used at least as early as 06/30/2006, and first used in commerce at least as early as 06/30/2006, and
`is now in use in such commerce. The applicant is submitting or will submit one specimen for each class showing the mark as used in commerce
`on or in connection with any item in the class of listed goods and/or services, consisting of a(n) package insert included with product.
`Specimen File1
`
`The applicant hereby appoints Lawrence R. Robins of Finnegan, Henderson, Farabow, Garrett & Dunner L.L.P., 901 New York Avenue, N.W.,
`Washington, District of Columbia, United States, 20001 to submit this application on behalf of the applicant. The attorney docket/reference
`number is 08727.0038-00000.
`
`Correspondence Information: Lawrence R. Robins
`901 New York Avenue, N.W.
`Washington, District of Columbia 20001
`202-408-4000(phone)
`202-408-4400(fax)
`docketing@finnegan.com (authorized)
`
`A fee payment in the amount of $325 will be submitted with the application, representing payment for 1 class(es).
`
`Declaration
`
`The undersigned, being hereby warned that willful false statements and the like so made are punishable by fine or imprisonment, or both, under
`18 U.S.C. Section 1001, and that such willful false statements, and the like, may jeopardize the validity of the application or any resulting
`registration, declares that he/she is properly authorized to execute this application on behalf of the applicant; he/she believes the applicant to be
`the owner of the trademark/service mark sought to be registered, or, if the application is being filed under 15 U.S.C. Section 1051(b), he/she
`believes applicant to be entitled to use such mark in commerce; to the best of his/her knowledge and belief no other person, firm, corporation, or
`association has the right to use the mark in commerce, either in the identical form thereof or in such near resemblance thereto as to be likely,
`when used on or in connection with the goods/services of such other person, to cause confusion, or to cause mistake, or to deceive; and that all
`statements made of his/her own knowledge are true; and that all statements made on information and belief are believed to be true.
`
`Signature: /Lawrence R. Robins/(cid:160)(cid:160)(cid:160)Date Signed: 02/28/2007
`Signatory's Name: Lawrence R. Robins
`Signatory's Position: Attorney for Applicant
`
`

`
`RAM Sale Number: 778
`RAM Accounting Date: 03/01/2007
`
`Serial Number: 77118853
`Internet Transmission Date: Wed Feb 28 17:37:05 EST 2007
`TEAS Stamp: USPTO/BAS-XX.XXX.X.X-2007022817370512113
`5-77118853-36091ce41d75af78e9d1b20fccf17
`a12d-CC-778-20070228173205945077
`
`

`
`

`
`FOR lNTR/WENOUS
`INFUSION ONLY
`
`RISK OF HYPERSENSITIVITY REACTIONS
`LIFBTHREATENING ANAPHYLACTIC REACTIONS, INCLUDING ANAPHYLACTIC SHOCK, HAVE
`BEEN OBSERVED IN PATIENTS DURING MYOZYME INFUSION.
`BECAUSE OF THE POTENTIAI. FOR SEVERE INFUSION REACTIONS, APPROPRIATE MEDICAL
`SUPPORT MEASURES SHOULD BE READILY AVAILABLE WHEN MYOZYME IS ADMINISTERED.
`
`DES RIPTRON
`
`MYOZYMFW (alglucosidase alia) consists of the
`human enzyme acid or-glucosidase (GAA),
`encoded by the most predominant of nine observed
`haplotypes of this gene. MYOZYME is produced by
`recombinant DNA technology in a Chinese hamster
`ovary cell line. Alglucosidase alfa degrades glycogen
`by catalyzing the hydrolysis of r1~1,4— and ot~1,6~
`glycosidic linkages of lysosomal glycogen.
`Alglucosidase alfa is a glycoprotein with a calculated
`mass of 99,377 daltons for the polypeptide chain,
`and a total mass of approximately 109,000 daltons,
`including carbohydrates. Alglucosidase alfa has a
`specific activity of 3 to 5 U/mg (one unit is defined
`as that amount of activity that results in the hydrolysis
`of 1 pmole of synthetic substrate per minute under
`the specified assay conditions). MYOZYME is intended
`for intravenous infusion. It is supplied as a sterile,
`nonpyrogenic, white to off—white, lyophilized cake
`or powder for reconstitution with 10.3 mL Sterile
`Water for injection, USP. Each 50 mg vial contains
`525 mg aiglucosidase alfa, 210 mg mannitol,
`0.5 mg polysorbate 80, 9.9 mg sodium phosphate
`dibasic heptahydrate, 31.2 mg sodium phosphate
`monobasic monohydrate. Following reconstitution as
`directed, each vial contains 10.5 mL reconstituted
`solution and a total extractable volume of 10 mt at
`5.0 mg/mL alglucosidase alfa. MYOZYME does not
`contain preservatives; each vial is for single use only.
`
`CLlNiC/J‘tl. PH./\RtVi:'5\CO§ QC-Y
`Mechanism of Action
`
`Pompe disease (glycogen storage disease type II,
`GSD ll, glycogcnosis type II, acid maltase deficiency)
`is an inherited disorder of glycogen metabolism
`caused by the absence or marked deficiency of the
`lysosomal enzyme GAA.
`in the infantileonset form, Pompe disease results in
`intralysosomal accumulation of glycogen in various
`tissues, particularly cardiac and skeletal muscles,
`and hepatic tissues, leading to the development of
`cardiomyopathy, progressive muscle weakness, and
`impairment of respiratory function.
`in the juvenile- and adult-onset forms, intralysosomal
`accumulation of glycogen is limited primarily to
`skeletal muscle, resulting in progressive muscle
`weakness. Death in all forms is usually related to
`respiratory failure.
`MYOZYME provides an exogenous source of
`GAA. Binding to mannose~6-phosphate receptors
`on the cell surface has been shown to occur via
`carbohydrate groups on the GAA molecule, after
`which it is internalized and transported into
`lysosomes, where it undergoes proteolytic cleavage
`
`that results in increased enzymatic activity. it then
`exerts enzymatic activity in cleaving glycogen.
`Pharmacokinetics
`
`The pharmacokinetics of alglucosidase alfa were
`evaluated in 13 patients of age ranging from
`1 month to 7 months with infantile-onset Pompe
`disease who received 20 mg/kg (as an approximate
`4Ahour infusion) or 40 mg/kg (as an approximate
`65-hour infusion) of MYOZYME every 2 weeks.
`The measurement of alglucosidase alfa plasma
`concentration was based on an activity assay using
`an artificial substrate. Systemic exposure was
`approximately dose proportional between the
`20 and 40 mg/kg doses (see Table 1).
`
`§ After Single Intravenous lnfuion of MYOZYME
`Pharmacokinetic
`Parameter
`
`62.L31
`8111141
`
`E Cmax (mcg/mL)
`AUCr lrncg«hr/mt
`CL (mL/hr/kg)
`Vss (m L/kg)
`
`The pharmacokinetics of alglucosidase alfa were
`also evaluated in a separate trial in 14 patients of
`age ranging from 6 months to 3.5 years with Pompe
`disease who received 20 mg/kg of MYOZYME as an
`approximate 4-hour infusion every 2 weeks. The
`pharmacokinetic parameters were similar to those
`observed for the 20 mg/kg dose group in the trial of
`patients of age ranging from 1 month to 7 months.
`Nineteen of 21 patients who received treatment with
`MYOZYME and had pharmacokinetics and antibody
`titer data available at Week 12 developed antibodies
`to alglucosidase alfa. Five patients with antibody
`titers 2 12,800 at Week 12 had an average increase
`in clearance of 50% (range 5% to 90%) from Week
`1 to Week 12. The other 14 patients with antibody
`titers < 12,800 at Week 12 had similar average
`clearance values at Week 1 and Week 12.
`
`CtiNICAL STUDIES
`
`The safety and efficacy of MYOZYME were assessed
`in 2 separate clinical trials in 39 Pompe disease
`patients, who ranged in age from 1 month to
`3.5 years at the time of first infusion.
`Study 1 was an international, multicenter, open~
`label, clinical trial of 18 infantile-onset Pompe
`disease patients. This study was conducted between
`2003 and 2005. Patients were randomized equally
`to either 20 mg/kg or 40 mykg MYOZYME every
`
`two weeks, with length of treatment ranging from
`S2 to 106 weeks. Enrollment was restricted to patients
`ages 7 months or less at first infusion with clinical
`signs of Pompe disease, with cardiac hypertrophy,
`and who did not require ventilatory support at
`study entry.
`Efficacy was assessed by comparing the proportions
`of MYOZYMEvtreatcd patients who died or needed
`invasive ventilator support with the mortality
`experience of an historical cohort of untreated
`infantile-onset Pompe patients with similar age and
`disease severity, In the historical cohort, 61 untreated
`patients with infantileonset Pompe disease
`diagnosed by age 6 months, born between 1982
`and 2002, were identified by a retrospective review
`of medical charts. By the age of 18 months, only
`one of the 61 historical control patients was alive
`(98% mortality), indicating the poor outcome of
`patients who are left untreated.
`Within the first 12 months of treatment, 3 of
`18 MYOZYME-treated patients required invasive
`ventilatory support (17%, with 95% confidence
`interval 4% to 41%); there were no deaths.
`With continued treatment beyond 12 months,
`4 additional patients required invasive ventilatory
`support, after receiving between 13 and 18 months
`of MYOZYME treatment; 2 of these 4 patients died
`after receiving 14 and 25 months of treatment, and
`after receiving 1 1 days and 7.5 months of invasive
`ventilatory support, respectively. No other deaths
`have been reported through a median fol|ow~up of
`20 months, and all 16 surviving patients continue to
`be followed. Survival without invasive ventilatory
`support was substantially greater in the MYOZYME-
`treatcd patients in this study than would be expected
`compared to the poor survival of the historical
`control patients. No differences in outcome were
`observed between patients who received 20 mg/kg
`versus 40 mg/kg.
`Other outcome measures in this study included
`unblinded assessments of motor function by the
`Alberta infant Motor Scale (AIMS). The AIMS is a
`measure of infant motor performance that assesses
`motor maturation of the infant through age 18
`months and is validated for comparison to normal.
`healthy infants. AlMS—assessed gains in motor
`function occurred in 13 patients. In the majority of
`patients, motor function was substantially delayed
`compared to normal infants of comparable age. The
`continued effect of MYOZYME treatment over time
`on motor function is unknown. Two of 9 patients
`who had demonstrated gains in motor function after
`12 months of MYOZYME treatment and continued
`to be followed regressed despite ongoing treatment.
`Changes from baseline to Month 12 in left ventricular
`mass index (LVMI), an evaluation of bioactivity, were
`measured by echocardiography. For the 15 patients
`with both baseline and Month 12 echocardiograms,
`all had decreases from baseline in LVMI (mean
`decrease 118 g/ml, range 45 to 193 g/m2).
`The magnitude of the decrease in LVMI did not
`correlate with the clinical outcome measure of
`ventilatonfree survival.
`
`Study 2 is an ongoing, international, multicenter,
`non—rand0mized, open«label clinical trial that
`enrolled 21 patients who were ages 3 months to
`3.5 years at first treatment. All patients received
`20 mg/kg MYOZYME every other week for up to
`104 weeks. Five of 21 patients were receiving invasive
`ventilatory support at the time of first infusion.
`The primary outcome measure was the proportion
`of patients alive at the conclusion of treatment.
`At the 52-week interim analysis, 16 of 21 patients
`were alive. Sixteen patients were free of invasive
`ventilatory support at the time of first infusion:
`of these, 4 died, 2 required invasive ventilaiory
`support, and 10 were free of invasive ventilatory