-67
`PATENT
`Atty. Docket No.: AEGIS1210
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`Applicants: Meezan et al. Art Unit: 1616
`Application No.: 11/127,786 Examiner: J.H. Alstrum Acevedo
`Filed: May 11, 2005 Conf. No.: 5393
`Title: ABSORPTION ENHANCERS FOR DRUG ADMINISTRATION
`MAIL STOP AMENDMENT
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`TRANSMITTAL SHEET
`Sir:
`Transmitted herewith for the above-identified application please find:
`1. Amendment (28 pgs.);
`2. Three-Month Petition for Extension of Time (1 pg., in dup.);
`3. Replacement Drawings (3 sheets);
`4. Information Disclosure Statement (2 pgs.);
`5. Form PTO -1449 (1 pg.);
`6. Two References;
`7. Terminal Disclaimer (3 pgs.); ,
`8. Declaration under 37 C.F.R. §1.132 (4 pgs.);
`9. Check number 586657 in the amount of $755.00; and
`10. Return Receipt Postcard.
`CERTIFICATE OF MAILING BY "EXPRESS MAIL"
`"EXPRESS MAIL" LABEL NUMBER EM 023 788 864 US DATE OF DEPOSIT August 13, 2007
`I HEREBY CERTIFY THAT THIS PAPER OR FEE IS BEING DEPOSITED WITH THE UNITED STATES POSTAL SERVICE "EXPRESS MAIL POST
`OFFICE TO ADDRESSEE" SERVICE UNDER 37 CFR 1.10 ON THE DATE INDICATED ABOVE AND IS ADDRESSED TO: MAIL STOP
`AMENDMENT, COMMISSIONER FOR PATENTS, P.O. BOX 1450 , ALEXANDRIA, VA 22313-1450.
`Tim Lasher
`(TYPED OR PRINTED NAME OF PERSON MAILING PAPER) (SIGNATURE OF PERS ILING PAPER OR FEE)
`GT\6538152.1
`356894-12
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`In re Application of:
`Meezan et al.
`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 2
`PATENT
`Atty Docket No.: AEGIS1210
`Check number 586657 in the total amount of $755.00 is enclosed as payment for the
`three-month Extension of Time fee ($225.00), Terminal Disclaimer fee ($65.00) and Information
`Disclosure Statement fee ($180.00). No other fee is deemed necessary with the filing of this
`paper. However if any fees are due, the Commissioner is hereby authorized to charge any fees,
`or make any credits, to Deposit Account No. 07-1896 referencing the above-identified attorney
`docket number. A copy of this Transmittal Sheet is enclosed.
`Date: August 13, 2007
`DLA PIPER US LLP
`4365 Executive Drive, Suite 1100
`San Diego, California 92121-2133
`USPTO Customer No. 28213
`Respectfully submitted,
`Lisa . Haile, J.D., Ph.D.
`Registration No. 38,347
`Telephone: (858) 677-1456
`Facsimile: (858) 677-1465
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`AUG 1 3 2007 PATENT
`Atty. Docket No.: AEGIS1210
`iR
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`Applicants: Meezan et al. Art Unit: 1616
`Application No.: 11/127,786 Examiner: J.H. Alstrum Acevedo
`Filed: May 11, 2005 , Conf. No.: 5393
`Title: ABSORPTION ENHANCERS FOR DRUG ADMINISTRATION
`MAIL STOP AMENDMENT
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`AMENDMENT
`Sir:
`Responsive to the Office Action mailed February 12, 2007, please amend the above-
`identified application as follows:
`Amendments to the Specification are reflected beginning on page 2 of this paper.
`Amendments to the Claims are reflected in the listing of claims which begins on page 7
`of this paper.
`Remarks/Arguments begin on page 14 of this paper.
`CERTIFICATE OF MAILING BY "EXPRESS MAIL"
`-1- 1
`\
`0811 0
` 0 1
`"EXPRESS MAIL" LABEL NUMBER EM 023 788 864 US DATE OF DEPOSIT August 13, 2007
`I HEREBY CERTIFY THAT THIS PAPER OR FEE IS BEING DEPOSITED WITH THE UNITED STATES POSTAL SERVICE "EXPRESS MAIL POST
`OFFICE TO ADDRESSEE" SERVICE UNDER 37 CFR 1.10 ON THE DATE INDICATED ABOVE AND IS ADDRESSED TO: MAIL STOP
`AMENDMENT, COMMISSIONER FOR PATENTS, P.O. BOX 1450 , ALEXANDRIA, VA 22313-1450.
`Tim Lasher
`(TYPED OR PRINTED NAME OF PERSON MAILING PAPER) (SIGNATURE OF PERSO ING PAPER OR FEE)
`GT\6522580.2
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`In re Application of:
`Meezan et al.
`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 2
`Amendments to the Specification
`PATENT
`Atty Docket No.: AEGIS1210
`Please replace paragraph [0025] of the specification with the following amended
`paragraph:
`[0025] In one aspect, the invention provides a method of controlling caloric intake by
`administering a composition having a therapeutic effective amount of exendin-4, or related GLP-
`1 peptide, with an effective amount of INTRAVAIL ® Intravail alkyl saccharide.
`Please replace paragraph [0026] of the specification with the following amended
`paragraph:
`[0026] In another aspect, the invention provides a method of controlling blood glucose levels in a
`subject by administering to a subject a composition comprising a therapeutic effective amount of
`exendin-4, or related GLP-1 peptide, with an effective amount of INTRAVAIL ® Intravail alkyl
`saccharide.
`Please replace paragraph [0030] of the specification with the following amended
`paragraph:
`[0030] Figure 3 is a graph showing the effect of intranasal (closed triangles) and intraperitoneal
`(IP) injection (closed circles) administration of exendin-4/0.25%TDM and IP injection of saline
`alone, minus TDM (open circles) in reducing blood glucose levels following IP injection er-al
`administration of glucose (i.e., in a so-called "glucose tolerance test").
`Please replace paragraph [0045] of the specification with the following amended
`paragraph:
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`Page 3
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`[0045] The surfactants of the invention have a hydrophobic alkyl group linked to a hydrophilic
`hydrophobic saccharide. The linkage between the hydrophobic alkyl group and the hydrophilic
`saccharide can include, among other possibilities, a glycosidic, thioglycosidic (Horton), amide
`(Carbohydrates as Organic Raw Materials, F. W. Lichtenthaler ed., VCH Publishers, New York,
`1991), ureide (Austrian Pat. 386,414 (1988); Chem. Abstr. 110:137536p (1989); see Gruber, H.
`and Greber, G., "Reactive Sucrose Derivatives" in Carbohydrates as Organic Raw Materials, pp.
`95-116) or ester linkage (Sugar Esters: Preparation and Application, J. C. Colbert ed., (Noyes
`Data Corp., New Jersey), (1974)). Further, preferred glycosides can include maltose, sucrose,
`and glucose linked by glycosidic linkage to an alkyl chain of about 9-16 carbon atoms, e.g.,
`nonyl-, decyl-, dodecyl- and tetradecyl sucroside, glucoside, and maltoside. Again, these
`compositions are amphipathic and nontoxic, because they degrade to an alcohol and an
`oligosaccharide.
`Please replace paragraph [0051] of the specification with the following amended paragraph:
`[0051] Accordingly, a subject treated with surfactant compositions of the invention having at
`least one alkyl glycoside, e.g. tetradecylmaltoside (TDM; or INTRAVAIL ® Intravail A), at a
`concentration of about 0.125% by weight of alkyl glycoside two times per day, or three times per
`day, or more .depending on the treatment regimen consumes about 200 to 300 micrograms per
`day total of TDM. So, the effective dose of the TDM is at least 1000X fold lower than (i.e.,
`1/1000) of the NOAEL, and falls far below 1% of the NOAEL, which is the acceptable daily
`intake; or in this case about 1/50,000 of the acceptable daily intake.. Stated another way, alkyl
`glycosides of the present invention have a high NOAEL, such that the amount or concentration
`of alkyl glycosides used in the present invention do not cause an adverse effect and can be safely
`consumed without any adverse effect.
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`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 4
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`Please replace paragraph [0117] of the specification with the following amended
`paragraph:
`[0117] Stability of the alkyl glycoside depends, in part, on the number of carbon atoms, or
`branching length of the alkyl chain, with tetradecylmaltoside (TDM) having the greatest effect;
`but other highly branched long alkyl chains including DDM also have stabilizing effects. In
`contrast to Hovgaard-1, which described the preference for a high alkyl glycoside to drug ratio,
`the instant invention shows that this ratio is much lower. For example, alkyl glycosides in the
`range of about 0.01% to about 6% by weight result in good stabilization of the drug; whereas
`Hovgaard-1 shows stabilization is only achieved at much higher ratios of alkyl glycosides to
`drug (10:1 and 16:1). Even more interesting, alkyl glycosides of the invention in the range of
`about 0.01% to about 6% have increased bioavailability (see FIG. 1). This is in sharp contrast to
`Hovgaard-2, which showed relatively low bioavailability (0.5-1%) at the high alkyl glycoside
`ratios (10:1 and 16:1).
`Please replace paragraph [0135] with the following amended paragraph:
`[0135] Intranasal administration of drugs or agents are possible in animal models e.g. mice and
`rats, although the nasal opening in is very small. In the experiments and results described herein,
`an anesthesia-induced hyperglycemia model was used (described in Examples above).
`Hyperglycemic animals were induced by an intraperitoneal (IP) injection containing xylazine-
`ketamine and blood glucose levels were monitored over a period of time. Immediately after the
`xylazine-ketamine injection, there was an increase in the blood glucose levels as shown in FIG. 2
`(closed dark circles), and blood glucose levels were about 450 mg/d1. The increase in blood
`glucose levels was attributed to the inhibition of pancreatic insulin secretion. Blood glucose
`levels peak to about 482 mg/dl by 30 minutes after the xylazine-ketamine injection (FIG. 2).
`Then, at approximately 33 minutes after the xylazine-ketamine injection, 6 p.L of insulin
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`(Humalog) (HUMALOG ®) in 0.25% tetradecylmaltoside (TDM; or INTRAVAIL ® Intravail A)
`was administered intranasally using a long thin micropipette tip, and blood glucose levels were
`monitored at about 15 minute intervals. After administration of the 0.25% TDM/insulin
`composition, there was a rapid decrease in blood glucose levels, reaching a low of about 80
`mg/dl at about the 60 minute time point, or about 30 minutes after the insulin administration
`(FIG. 2). At about the 75 minute time point, blood glucose levels gradually returned to the
`baseline level in a normoglycemic mouse, or about 80-100 mg/dl.
`Please replace Table 1 at p.44 with the following amended table:
`TABLE I
`Effect of Eye Drops Containing Insulin Plus Various Concentrations of Dodecyl Maltoside
`on Blood Glucose Values (in m dl in Rat
`Dodecyl Maltoside Concentration
`0.125% 0.25% 0.375% 0.50%
`Time (min) Blood Glucose Concentrations (mg/di)
`-20 305±60 271±38 305±51 375±9
`-10 333±58 295±32 308±27 366± 12
`0 338±67 323 ± 62 309±32 379±4
`30 349±64 250±48 212± 18 297± 18
`60 318±38 168±22 134±4 188±25
`90 325 ± 57 188 ± 55 125 ± 12 -1-44 141 ± 13
`120 342 ± 78 206 ± 63 119 ± 19 123 ± 5
`Please replace the header of Example 5 at page 47, with the following amended title:
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`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 6
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`Atty Docket No.: AEGIS1210
`OCULAR ADMINISTRATION OF ALKYL SACCHARIDES PLUS GLUCAGON
`INSULIN PRODUCES HYPERGLYCEMIC EFFECTS IN VIVO
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`Application No.: 11/127,786
`Filed: May 11, 2005
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`Amendments to the Claims
`Please amend claims 1, 4-6, 12, 14-18, 20-31, 33-38, 40-42, and 44-46 as provided
`below.
`The listing of claims will replace all prior versions, and listings of claims in the
`application.
`Listing of Claims:
`1. (Currently Amended) A surfactant composition comprising o€ at least one alkyl
`glycoside and/or at least one saccharide alkyl ester, and when admixed with a drug, wherein the
`surfactant maintains stabilizes the biological activity and increases the bioavailability, of the
`drug[[.]]
`wherein the drug is selected from the group consisting of insulin, glucagon and
`exendin-4, and wherein the alkyl glycoside is selected from the group consisting of sucrose
`dodecanoate, dodecyl maltoside, and tridecyl maltoside.
`2. (Withdrawn) The composition of claim 1, wherein the drug is a peptide or a
`protein.
`3. (Original) The composition of claim 1, wherein the surfactant has a high no
`observable adverse effect level.
`4. (Currently Amended) The composition of claim 1, wherein the surfactant has a
`high no observable adverse effect level at least 10 times higher than the an acceptable daily
`intake amount of the surfactant.
`5. (Currently Amended) The composition of claim 1, wherein the surfactant has a
`high no observable adverse effect level at least 100 times higher than the an acceptable daily
`intake amount of the surfactant.
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`6. (Currently Amended) The composition of claim 1, wherein the a surfactant has a
`high no observable adverse effect level at least 1000 times higher than an acceptable the daily
`intake amount of the surfactant.
`7. (Original) The composition of claim 1, wherein the surfactant is a physiological
`non-irritant.
`8. (Original) The composition of claim 1, wherein the surfactant has from about 10
`to 16 carbon atoms.
`9. (Original) The composition of claim 1, wherein the surfactant and the drug are
`administered to subjects.
`10. (Original) The composition of claim 1, wherein the surfactant and the drug are
`administered to humans.
`11. (Original) The composition of claim 1, wherein the surfactant has anti-bacterial
`activity.
`12. (Currently Amended) The composition of claim 1, wherein the surfactant and the
`drug do not enter the hepatic portal blood system of a subject.
`13. (Original) The composition of claim 1, wherein the surfactant is stable for at least
`six months from about 4°C to 25°C.
`14. (Currently Amended) The composition of claim 1, wherein the surfactant is at a
`concentration is from of about 0.01% to 20% (w/v).
`15. (Currently Amended) The composition of claim 1, wherein the surfactant
`concentration is at a concentration of from about 0.01% to 5% (w/v).
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`16. (Currently Amended) The composition of claim 1, wherein the surfactant is at a
`concentration of is from about 0.01% to 2% (w/v).
`17. (Currently Amended) A therapeutic composition comprising e€ at least one
`biologically active compound(s) and at least one surfactant, wherein the surfactant is further
`comprised of at least one alkyl glycoside and/or saccharide alkyl ester and wherein said
`composition maintains stabilizes the biological activity of the a drug, for at least about 6 months
`from about 4°C to 25°C, wherein the drug is exendin-4.
`18. (Currently Amended) The composition of claim 17, wherein the pH of the
`composition has a pH is less than 8.0.
`19. (Original) The composition of claim 17, wherein the composition is stable for at
`least six months from about 4°C to 25°C.
`20. (Currently Amended) The composition of claim 17, wherein the composition has
`a concentration of is from about 0.01% to 20% (w/v).
`21. (Currently Amended) The composition of claim 17, wherein the composition has
`a concentration of is from about 0.01% to 5% (w/v).
`22. (Currently Amended) The composition of claim 17, wherein the composition has
`a concentration of is from about 0.01% to 2% (w/v).
`23. (Currently Amended) [[A]] The stable therapeutic composition according to
`claim 17, wherein the composition is formulated for mucosal administration to a subject.
`24. (Currently Amended) [[A]] The stable therapeutic composition according to claim
`17, wherein the administration to a the subject yields enhanced mucosal delivery of said
`biologically active compound(s) comprising:
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`a) a peak concentration (Cmax) of the said biologically active compound(s) in
`a CNS tissue or fluid or in a blood plasma of the said subject that is about 15% or greater
`as compared to a peak concentration of the biologically active compounds in CNS or
`blood plasma following intramuscular injection of an equivalent concentration of the
`biologically active compound(s) to the subject;
`b) an area under concentration curve (AUC) of the biologically active
`compound(s) in the central nervous system (CNS) tissue or fluid or in the blood plasma
`of the subject that is 20% or greater compared to an AUC of biologically active
`compound(s) in CNS or blood plasma following intramuscular injection of an equivalent
`concentration of the biologically active compound(s) to the said subject; or
`c) a time to maximal concentration (tmax ) of the biologically active
`compound(s) in a central nervous system (CNS) tissue or fluid or in the blood plasma of
`the subject between about 0.1 to 1.0 hours.
`25. (Currently Amended) The therapeutic composition of claim 17, wherein the
`composition following mucosal administration to the a subject yields a peak
`concentration (Cm ) of the biologically active compound(s) in the CNS tissue or fluid or
`in a blood plasma of the subject that is 20% or greater as compared to a peak
`concentration of the biologically active compound(s) in the CNS tissue or fluid or blood
`plasma following intramuscular injection of an equivalent concentration of the
`biologically active compound(s) to the subject.
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`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 11
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`Atty Docket No.: AEGIS1210
`26. (Currently Amended) The therapeutic composition of claim 17, wherein the
`composition following mucosal administration to a the subject yields a peak concentration (Cmax)
`of the biologically active compound(s) in the CNS tissue or fluid or in the blood plasma of the
`subject that is 50% or greater as compared to a peak concentration of the biologically active
`compound(s) in the CNS or blood plasma following intramuscular injection of an equivalent
`concentration or dose of the said biologically active compound(s) to the subject.
`27. (Currently Amended) The therapeutic composition of claim 17, wherein said
`composition following mucosal administration to a said subject yields an area under
`concentration curve (AUC) of the said biologically active compound(s) in the said CNS tissue or
`fluid or in the blood plasma of the subject that is 20% or greater compared to an AUC of the said
`biologically active compound(s) in the said CNS or blood plasma following intramuscular
`injection of an equivalent concentration or dose of the said biologically active compound(s) to
`the said subject.
`28. (Currently Amended) The therapeutic composition of claim 17, wherein the
`composition following mucosal administration to a the subject yields an area under concentration
`curve (AUC) of the said biologically active compound(s) in the CNS tissue or fluid or in the
`blood plasma of the subject that is 50% or greater compared to an AUC of the biologically active
`compound(s) in the said CNS or blood plasma following intramuscular injection of an equivalent
`concentration of the biologically active compound(s) to the subject.
`29. (Currently Amended) The therapeutic pharmaceutical composition of claim 17,
`wherein the composition following mucosal administration to a the subject yields a time to
`maximal plasma concentration (t.a.) of the biologically active compound(s) in the CNS tissue or
`fluid or in the blood plasma of the subject between about 0.1 to 1.0 hours.
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`Filed: May 11, 2005
`Page 12
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`30. (Currently Amended) The pharmaceutical composition of claim 17, wherein the
`composition following mucosal administration to a the subject yields a time to maximal plasma
`concentration (t.) of the biologically active compound(s) in the CNS tissue or fluid or in the
`blood plasma of the subject between about 0.2 to 0.5 hours.
`31. (Currently Amended) A method of administering a drug composition comprising
`e€ a surfactant having at least one alkyl glycoside and/or saccharide alkyl ester mixed with at
`least one drug and delivered to a subject, wherein the alkyl has from about 10 to 24 carbon
`atoms, and the surfactant increases the stability and bioavailability of the drug.
`32. (Original) The method of claim 31, wherein the surfactant has a high no
`observable adverse effect level.
`33. (Currently Amended) The method of claim 31, wherein the surfactant has a high
`no observable adverse effect level 10 times higher than an acceptable the daily intake amount of
`the surfactant.
`34. (Currently Amended) The method of claim 31, wherein the surfactant has a high
`no observable adverse effect level 100 times higher than an acceptable the daily intake amount of
`the surfactant.
`35. (Currently Amended) The method of claim 31, wherein the surfactant has a high
`no observable adverse effect level 1000 times higher than an acceptable the daily intake amount
`of the surfactant.
`36. (Currently Amended) The method of claim 31, wherein the surfactant reduces
`variance in the bioavailability variance from patient to patient.
`37. (Currently Amended) The method of claim 31, wherein the composition does not
`enter the hepatic portal blood system of a subject.
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`Filed: May 11, 2005
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`38. (Currently Amended) The method of claim 31, wherein the pI4-ef the
`composition has a pH is less than 8.0.
`39. (Original) The method of claim 31, wherein the composition is stable for at least
`six months from about 4°C to 25°C.
`40. (Currently Amended) The method of claim 31, wherein the composition has a
`concentration of is from about 0.01% to 20% (w/v).
`41. (Currently Amended) The method of claim 31, wherein the composition has a
`concentration of is from about 0.01% to 5% (w/v).
`42. (Currently Amended) The method of claim 31, wherein the composition has a
`concentration of is from about 0.01% to 2% (w/v).
`43. (Original) The method of claim 31 wherein the composition is administered to
`the mucosal membranes or tissue of a subject.
`44. (Currently Amended) The composition method of claim 1, wherein the
`composition is further comprises comprised of an enteric coating.
`45. (Currently Amended) The composition method of claim 1, wherein the alkyl
`glycoside is tetradecylmaltoside (TDM) or dodecylmaltoside (DDM).
`46. (Currently Amended) The method of claim 45, wherein the TDM or DDM has
`anti-bacterial activity.
`47 to 138. (Cancelled).
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`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 14
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`Atty Docket No.: AEGIS1210
`REMARKS
`The remarks are in response to the Office Action dated February 12, 2007. Claims 1, 4-6,
`12, 14-18, 20-31, 33-38, 40-42, and 44-46 have been amended. Claims 47-138 were previously
`cancelled without prejudice. Subsequent to the entry of the present amendment, claims 1 and 3-
`46 will be pending and at issue. These amendments and additions add no new matter as the
`claim language is fully supported by the specification and original claims.
`Information Disclosure Statement
`The Office Action alleges that the manuscripts listed in paragraph [0141] fail to comply
`with the provisions of 37 C.F.R §§1.98(b) because the references were not submitted in a
`separate paper and may not be incorporated into the specification. Applicants respectfully
`submit that four of the articles cited by the Examiner, and provided below, were previously
`submitted in an information disclosure statement filed on October, 31 2005. Accordingly,
`Applicants respectfully request withdrawal of the Examiner's objection with regard to the
`references.
`Hovgaard et al., (1996) "Stabilization of insulin by alkylmaltosides: A
`spectroscopic evaluation," Int. J. Pharmaceutics 132:107-113.
`Hovgaard et al., (1996) "Stabilization of insulin by alkylmaltosides. B. Oral
`absorption in vivo in rats," Int. J. Pharmaceutics 132:115-121.
`Tetsuaki et al. (1997) "Lysis of Bacillus subtilis cells by glycerol and sucrose
`esters of fatty acids," Applied and Environmental Microbiology, 53(3):505-508.
`Watanabe et al., (2000) "Antibacterial carbohydrate monoesters suppressing cell growth
`of Streptococcus mutan in the presence of sucrose," Curr Microbiol 41(3): 210-213.
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`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 15
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`The Office Action also alleges that two additional manuscripts included in paragraph
`[0141] fail to comply with the provisions of 37 C.F.R §§1.98(b) because the references were not
`submitted in a separate paper and may not be incorporated into the specification. Attached
`herewith is a submission of an IDS on a form PTO/SB/08 1449 for consideration by the
`Examiner. Applicants respectfully request withdrawal of the objection.
`Rejections under 35 U.S.C. 112, First Paragraph
`Claims 17-46 are rejected under 35 U.S.C. §112, for allegedly failing to meet the written
`description requirement. Applicants respectfully traverse the rejection as it applies to the
`pending claims.
`It is well-established that "[a] objective standard for determining compliance with the
`written description requirement is, "does the description clearly allow persons of ordinary skill in
`the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012,
`10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555,
`1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement,
`an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing
`date sought, he or she was in possession of the invention, and that the invention, in that context,
`is whatever is now claimed".. See MPEP §2163.04.
`Applicants respectfully submit that support for claims 17-46 can be found in, for
`example, paragraph [0048] of the specification as filed. Further, in view of the art known at the
`time of filing, Applicants submit that the specification, as filed, conveys with reasonable clarity
`that the Applicants were in possession of the claimed invention as of the filing date.
`For example, the present specification highlights U.S. Patent No. 5,726,154 (hereafter
`"the `154 patent"), which is incorporated by reference in its entirety, which describes
`characteristics of similar therapeutic compositions to those claimed in the present invention. The
``154 patent describes aqueous mixtures of an effective amount of a surfactant (SDS) and an
`effective amount of organic acid in order to provide storage of calcitonin for up to 6 months at
`between 4°C - 25°C (see, e.g., Tables 1 and 2, columns 5 and 6 respectively of the `154 patent).
`MA6522580.2
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`In re Application of:
`Meezan et al.
`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 16
`PATENT
`Atty Docket No.: AEGIS1210
`Applicants submit that the `154 patent establishes what was known in the art at the time the
`application was filed and that the present invention amply demonstrates the Applicants were in
`possession of the invention at the time of filing. (see for example, claim 13 and paragraph [0006]
`of the specification as filed). Applicants further submit that the bioavailability data presented in,
`for example, Figure 1 and paragraphs [0117] and [0118], allow the skilled artisan to extrapolate
`pharmacokinetic parameters such as, for example, C max and AUC. Thus, Applicants respectfully
`submit that the specification clearly conveys with reasonable clarity to those skilled in the art
`that, as of the filing date, the Applicants were in possession of the claimed invention.
`Accordingly, withdrawal of rejection of claims 17-46 under 35 U.S.C. §112, first
`paragraph is respectfully requested.
`Rejections under 35 U.S.C. §112, First Paragraph (enablement)
`Claims 31-46 are rejected under 35 U.S.C. §112, first paragraph, as allegedly containing
`subject matter not described in the specification in such a way as to enable one of skill in the art
`to make or use the invention. Applicants respectfully traverse the rejection as it applies to the
`pending claims.
`Applicants respectfully submit that those of ordinary skill in the art would be able to
`utilize the present specification to determine appropriate therapeutic compositions to administer
`to a subject in need thereof. (see for example, paragraphs [0040]-[0045], among others).
`Applicants further submit that the skilled artisan would sufficiently understand the terms
`"subject" and "biologically active" provided in the specification, as filed, and respectfully direct
`the Examiner's attention to paragraphs [0035] and [0036] of the specification wherein example
`therapeutic peptides are disclosed.
`However, without acquiescing to the reasoning offered by the Office, and in order to
`advance prosecution of the instant application, Applicants have amended claims 1, 37, and 40-42
`to provide greater particularity to terms "subject" and "biologically active" thus, the rejection no
`longer applies to the claims. Support for the amendments may be found in Examples 3, 4, 5, 6
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`In re Application of:
`Meezan et al.
`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 17
`PATENT
`Atty Docket No.: AEGIS1210
`and 7 and, for example, in paragraphs [0026], [0030] and [0070], among others of the
`specification as filed. Paragraph [0070] of the present specification, for example, describes a
`number of agents known in the art to be biologically active against specific pharmacological
`targets. As such, Applicants submit that the skilled artisan would sufficiently understand term
`"biologically active" as described in the specification as filed. Further, paragraph [0010] of the
`specification as filed, for example, provides a description pertaining to a "subject" as follows:
`The present invention also provides a method of treating diabetes including
`administering to a subject in need thereof via the oral, ocular, nasal, nasolacrimal,
`inhalation or pulmonary, or oral cavity (sublingual or Buccal cell), a blood
`glucose reducing amount of a therapeutic composition, for example, an incretin
`mimetic agent or a functional equivalent thereof, and an absorption increasing
`amount of a suitable nontoxic, nonionic alkyl glycoside having a hydrophobic
`alkyl group joined by a linkage to a hydrophilic saccharide, thereby increasing the
`absorption of incretin mimetic agent or insulin and lowering the level of blood
`glucose and treating diabetes in the subject. (paragraph [0010])
`Thus, Applicants respectfully assert the skilled artisan would understand the term "subject" to
`encompass organisms with oral, ocular, nasal, etc., routes of administration and organisms
`subject to disease states such as, for example, diabetes. Applicants submit that the specification
`enables the skilled artisan to practice the claimed invention and respectfully request withdrawal
`of the rejection.
`Rejections under 35 U.S.C. X112, second paragraph
`Claims 2, 4-6, and 14-46 are rejected under 35 U.S.C. §112, second paragraph as
`indefinite for allegedly failing to particularly point out and distinctly claim the subject matter
`which applicant regards as the invention. Applicants respectfully traverse the rejection as it
`applies to the pending claims. Applicants respectfully submit that it appears that the Examiner's
`rejection of claim 24 in the Office Action dated February 12, 2007, should be directed to claim
`36. Accordingly, the following comments pertain, in part, to rejection of claim 36.
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`In re Application of:
`Meezan et al.
`Application No.: 11/127,786
`Filed: May 11, 2005
`Page 18
`PATENT
`Atty Docket No.: AEGIS1210
`Claims 20-22 and 40-42 are rejected as allegedly being confusing and indefinite because
`they claim a therapeutic composition and also refer to a composition concentration