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`Atty. Dkt. No. 016777/0454
`
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE-=tP
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`App 1cant:
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`JUL 11 2003
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`~
`
`Indu J. ISAACS
`
`1.
`
`Title:
`
`GLP-2 Formulations
`
`Appl. No.:
`
`09/750,022
`
`Filing Date: December 29, 2000
`
`Examiner:
`
`C.Kam
`
`Art Unit:
`
`1653
`
`1ECH CEN1ER '\ 600/2900
`
`AMENDMENT AND REPLY UNDER 37 C.F.R. §1.111
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`In reply to the Non-Final Office Action mailed on February 5, 2003, the due date for
`
`response having been extended three months to August 5, 2003, Applicant submits the
`
`following Amendment and Reply under 37 C.F.R. § 1.111.
`
`Applicants concurrently file herewith a Petition for Extension of Time under 37
`
`C.F.R. § l .136(a), with provision for the required fee, to extend the period for response for
`
`three months, up to and including August 5, 2003. If additional fees are necessary to prevent
`
`abandonment of this application, the Commissioner is hereby authorized to charge Deposit
`
`Account No. 19-0741.
`
`07/10/2003 CNGUYEN 00000149 09750022
`02 FC:1201
`84.00 OP
`18.00 OP
`03 FC:1202
`
`CFAD Exhibit 1010
`
`1
`
`

`

`- °I
`
`Atty. Dkt. No. 016777/0454
`
`IN THE CLAIMS:
`
`lndu J. ISAACS
`Serial No. 09/750,022
`
`In accordance with 37 C.F.R. § 1.121, please substitute for claims 1, 14, 15, and 32
`
`the following rewritten version of the same claims, as amended. The changes are shown
`
`explicitly in the attached "Version with Markings to Show Changes Made".
`
`1.
`
`(a)
`
`(Amended) A glucagon-like peptide-2 (GLP-2) formulation comprising:
`
`a medically us~ful amount of a naturally occurring GLP-2 peptide or an analog
`
`thereof;
`
`(b)
`
`a phosphate buffer in an amount sufficient to adjust the pH of the formulation
`
`to a physiologically tolerable level;
`
`L-histidine; and
`
`a bulking agent selected from the group consisting of mannitol and sucrose.
`
`(c)
`
`d
`
`14.
`
`(Amended) The GLP-2 formulation of claim 13, wherein the GLP-2 peptide
`
`has the sequence of a GLP-2 species from an animal selected from the group consisting of a
`
`primate, rat, mouse, porcine species, oxine species, bovine species, degu, hamster, guinea pig,
`
`fish, chicken, and human.
`
`-----
`
`-:;)--
`
`15.
`
`(Amended) The GLP-2 formulation of claim 14, wherein the GLP-2 peptide is
`
`0
`ro
`0 3 ____ 3_2_. __ T_h_e_G_L_P_-2_fo_rm_u_1_at_io_n_of_c_1_a_im_3_1_, w_h_er_e_in_th_e_G_L_P_-_2_1_·s_h-(G-ly_2_)_G_L_P_-2_. ______ _
`
`h(Gly2)GLP-2.
`
`Please add the following new claim.
`
`55.
`
`(a)
`
`(NEW) A GLP-2 formulation comprising:
`
`a medically useful amount of a naturally occurring GLP-2 peptide or an analog
`
`thereof;
`
`(b)
`
`a phosphate buffer in an amount sufficient to adjust the pH of the formulation
`
`to a physiologically tolerable level;
`
`(c)
`
`(d)
`
`L-histidine in an amount sufficient to stabilize the formulation; and
`
`a bulking agent selected from the group consisting ofmannitol and sucrose.
`
`002.982744.1
`
`-2-
`
`2
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`

`

`·,
`
`Atty. Dkt. No. 016777/0454
`
`lndu J. ISAACS
`Serial No. 091750,022
`
`I.
`
`Status of the Claims
`
`REMARKS
`
`By this amendment, claims 1, 14, 15, and 32 are amended and claim 55 is added.
`
`Upon entry of this Amendment, claims 1-55 will be pending.
`
`Exemplary support for the amendments to claims 1, 14, 15, and 32 is found
`
`throughout the specification. See page 1, line 20. Exemplary support for claim 55 is found
`
`on page 2, lines 24-32. Claim 55 is added to more clearly define claim scope.
`
`Because the foregoing amendments to not add new matter, entry thereof by the
`
`Examiner is respectfully requested.
`
`It is acknowledged that the Examiner notes that claims 36-42 are free of the prior art
`
`and that claims 23-30, 32-35, 47, and 48 would be allowable if written in independent form
`
`including all of the limitation of the base claim and any intervening claims.
`
`II.
`
`Claim Rejections - 35 U.S.C. § 103
`
`A.
`
`Rejection Of Claims 1-10, 22, And 49-54 As Being
`Allegedly Obvious Over Knudsen et al. In View Of
`Makino et al.
`
`Claims 1-10, 22, and 49-54 are rejected by the Examiner under 35 U.S.C. § 103 as
`
`being allegedly obvious over Knudsen et al. (WO 99/43361) ("Knudsen") in view of Makino
`
`et al. (U.S. Patent No. 4,985,244) ("Makino")~ The Examiner asserts that although Knudsen
`
`fails to disclose using histidine as a stabilizing agent in a pharmaceutical composition, the
`
`claimed invention would have been obvious to a person of ordinary skill in the art at the time
`
`the invention was made because Makino disclose using 5% (w/v%) of histidine as a
`
`stabilizing agent in a vaccine composition. Applicant respectfully traverses and requests
`
`reconsideration and withdrawal of the rejection.
`
`A proper rejection for obviousness under§ 103 requires consideration of two factors:
`
`( 1) whether the prior art would have suggested to those of ordinary skill in the art that they
`
`should make the claimed composition, or device, or carry out the claimed process, and
`
`002.9827 44.1
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`-3-
`
`3
`
`

`

`Atty. Dkt. No. 01677710454
`
`Indu J. ISAACS
`Serial No. 091750,022
`
`(2) whether the prior art would also have revealed that in making or carrying out the claimed
`
`invention, those of ordinary skill would have a reasonable expectation of success. Both the
`
`suggestion and the reasonable expectation of success must be found in the prior art. and not in
`
`the applicant's disclosure. In re Vaeck, 947 F.2d 488, 493, 20 USPQ2d 1438 (Fed. Cir.
`
`1991 ). In the present case, the examiner has failed to establish a prima facie case of
`
`obviousness for the following reasons.
`
`1.
`
`There is no Motivation to Combine
`the Teachings of Makino and Knudsen
`
`There is no teaching or suggestion in the cited prior art to combine the teachings of
`
`Makino with the teachings of Knudsen to obtain the claimed invention because the two
`
`references are directed to different types of compositions which are not interchangeable, and
`
`which have different properties and characteristics.
`
`Specifically, Knudsen teaches a pharmaceutical composition comprising a GLP-2
`
`derivative of improved solubility and/or stability. GLP-2 and derivatives thereof are peptides.
`
`In contrast, Makino teaches a stabilized live attenuated vaccine. A peptide is defined as "two
`
`or more amino acids joined by a peptide bond" (see attached definition from
`
`http://www.genome.gov/glossary.cfm?key=peptide). In contrast, a vaccine is defined as "a
`
`suspension of attenuated or killed microorganisms (bacteria, viruses or rickettsiae),
`
`administered for the prevention, amelioration, or treatment of infectious diseases" (see
`
`attached definition from http://cancerweb.ncl.ac.uk/cgi-bin/omd?vaccine).
`
`While a peptide is a compound formed by joining amino acids, a vaccine comprises
`
`complex attenuated or killed organisms. Since a peptide is entirely different from a vaccine, a
`
`person of ordinary skill in the art would not expect the stability of a vaccine in a solution to
`
`have any bearing on the stability of a peptide in the same solution. Therefore, the cited
`
`references lack the requisite teaching or suggestion to motivate a person of ordinary skill in
`
`the art to combine the references. Moreover, the Examiner has failed to provide any
`
`reasoning to support the assertion that a person of ordinary skill in the art would have been
`
`motivated to combine the teachings of the cited art to obtain the claimed invention.
`
`002.982744.1
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`-4-
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`4
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`

`

`Atty. Dkt. No. 016777/0454
`
`• Indu J. ISAACS
`
`Serial No. 091750,022
`
`2.
`
`One of Ordinary Skill in the Art Would Not Have had a
`Reasonable Expectation of Success in Obtaining the Claimed
`Invention by Combining the Teachings of Makino and Knudsen
`
`A person of ordinary skill in the art would not have had a reasonable expectation of
`
`success in adding a stabilizing agent known to stabilize vaccine solutions to a pharmaceutical
`
`composition comprising a GLP-2 peptide derivative. As discussed above, a peptide is
`
`entirely different from a vaccine. Thus, a person of ordinary skill in the art would not expect
`
`that a stabilizer known to stabilize vaccines would also stabilize a pharmaceutical
`
`composition comprising a GLP-2 peptide derivative.
`
`In particular, Applicant directs the Examiner's attention to page 5 of the March 8,
`
`2002, Office Action for the present application where the Examiner stated that Knudsen and
`
`Makino do not teach the claimed invention because "it is not known whether histidine can
`
`stabilize GLP-2 or its analogs in the GLP-2 formulation."
`
`For the above reasons, the Examiner has failed to establish aprimafacie case of
`
`obviousness for the rejection of the claims over Knudsen in view of Makino. Withdrawal of
`
`this ground for rejection is respectfully requested.
`
`B.
`
`Rejection Of Claims 11, 12, And 31 As Being Allegedly
`Obvious Over Knudsen In View Of Makino, And Further
`In View Of Hora et al.
`
`Claims 11, 12, and 31 are rejected by the Examiner as being allegedly unpatentable
`
`over Knudsen in view of Makino, as applied to claims 1-10 above, and further in view of
`
`Hora et al. (U.S. Patent No. 5,997,856) ("Hora"). Applicant respectfully traverses this ground
`
`for rejection.
`
`As discussed above, the Examiner has failed to establish a prima facie case of
`
`obviousness for the rejection of the claims over Knudsen in view of Makino. Hora does not
`
`remedy the deficiencies of Knudsen and Makino. Therefore, claims 11, 12, and 31 are not
`
`obvious over Knudsen in view of Makino and further in view of Hora. Applicant respectfully
`
`traverses and requests reconsideration and withdrawal of the rejection.
`
`002.9827 44.1
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`-5-
`
`5
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`

`

`..
`
`Atty. Dkt. No. 016777/0454
`
`Indu J. ISAACS
`Serial No. 09/750,022
`
`C.
`
`Rejection Of Claims 13-15 And 17-20 As Being Allegedly
`Obvious Over Knudsen In View Of Makino, And Further
`In View Of Drucker et al.
`
`Claims 13-15 and 17-20 are rejected by the Examiner as being allegedly unpatentable
`
`over Knudsen in view of Makino, as applied to claim 1 above, and further in view of Drucker
`
`et al. (WO 97 /39032) ("Drucker A"). Applicant respectfully traverses this ground for
`
`rejection.
`
`As discussed above, the Examiner has failed to establish a prima facie case of
`
`obviousness for the rejection of the claims over Knudsen in view of Makino. Drucker does
`
`not remedy the deficiencies of Knudsen and Makino. Therefore, claims 13-15 and 17-20 are
`
`not obvious over Knudsen in view of Makino and further in view of Drucker. Applicant
`
`respectfully traverses and requests reconsideration and withdrawal of the rejection.
`
`D.
`
`Rejection of claims 16 and 21 As Being Allegedly Obvious
`Over Knudsen In View Of Makino, And Further In View
`Of Thim et al.
`
`Claims 16 and 21 are rejected by the Examiner as being allegedly unpatentable over
`
`Knudsen in view of Makino, as applied to claim 1 above, and further in view of Thim et al.
`
`(U.S. Patent No. 5,912,229) ("Thim"). Applicant respectfully traverses this ground for
`
`rejection.
`
`As discussed above, the Examiner has failed to establish a prima facie case of
`
`obviousness for the rejection of the claims over Knudsen in view of Makino. Thim does not
`
`remedy the deficiencies of Knudsen and Makino. Therefore, claims 16 and 21 are not
`
`obvious over Knudsen in view of Makino and further in view of Thim. Applicant
`
`respectfully traverses and requests reconsideration and withdrawal of the rejection.
`
`E.
`
`Rejection Of Claims 43-46 As Being Allegedly Obvious
`Over Knudsen In View Of Makino, And Further In View
`Of Drucker et al.
`
`Claims 43-46 are rejected by the Examiner as being allegedly unpatentable over
`
`Knudsen in view of Makino as applied to claim 1 above, and further in view of Drucker et al.
`
`002.9827 44.1
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`-6-
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`6
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`

`

`...
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`•'
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`Atty. Dkt. No. 016777/0454
`
`Indu .J. ISAACS
`Serial No. 09/750,022
`
`(U.S. Patent No. 5,952,301) ("Drucker B"). Applicant respectfully traverses this ground for
`
`rejection.
`
`As discussed above, the Examiner has failed to establish a prima facie case of
`
`obviousness for the rejection of the claims over Knudsen in view of Makino. Drucker B does
`
`not remedy the deficiencies of Knudsen and Makino. Therefore, claims 43-46 are not
`
`obvious over Knudsen in view of Makino and further in view of Drucker B. Applicant
`
`respectfully traverses and request reconsideration and withdrawal of the rejection.
`
`CONCLUSION
`
`As the above-presented amendments and remarks address and overcome all of the
`
`rejections presented by the Examiner, withdrawal of the rejections and allowance of the
`
`claims are respectfully requested.
`
`If the Examiner has any questions concerning this application, he or she is requested
`
`to contact the undersigned.
`
`Respectfully submitted,
`
`Michele M. Simkin
`Attorney for Applicant
`Registration No. 34, 717
`
`Date _tlJ~, '---~_l, _5-r.--_6J/0_3. _ _ _
`
`}
`
`I
`
`FOLEY & LARDNER
`Washington Harbour
`3000 K Street, N. W., Suite 500
`Washington, D.C. 20007-5109
`Telephone:
`(202) 672-5538
`Facsimile:
`(202) 672-5399
`
`, sli~\ltd additional fees be ne~essary in connedtidn with the filing orthis paper, or if a iJ~tltio\i·for exte~i3'n of ·•
`time, is required for timely· acceptance of sam~, .the ·comtiri~s~one~is hereby 'aptbop.zeq to c*ge l)epm;it ··•
`>Account No;•J 9-07 41 for any sucn fees;· and applicant( s) hereby petition for ariy nedded extension of time.
`
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`002.982744.1
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`-7-
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`7
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`

`

`·'
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`•
`
`Atty. Dkt. No. 016777/0454
`
`VERSION WITH MARKINGS TO SHOW CHANGES MADE
`
`1.
`
`(a)
`
`(Amended) A glucagon-like peptide-2 (GLP-2} formulation comprising:
`
`a medically useful amount of a naturally occurring GLP-2 peptide or an analog
`
`thereof;
`
`(b)
`
`a phosphate buffer in an amount sufficient to adjust the pH of the formulation
`
`to a physiologically tolerable level;
`
`L-histidine; and
`
`a bulking agent selected from the group consisting ofmannitol and sucrose.
`
`( c)
`
`(d)
`
`14.
`
`(Amended) The GLP-2 formulation of claim 13, wherein the GLP-2 peptide
`
`has the sequence of a GLP-2 species from [n] an animal selected from the group consisting of
`
`a primate, rat, mouse, porcine species, oxine species, bovine species, degu, hamster, guinea
`
`pig, fish, chicken, and human.
`
`15.
`
`(Amended) The GLP-2 formulation of claim 14, wherein the GLP-2 peptide is
`
`[h[Gly2]GLP-2] h(Gly2}GLP-2.
`
`32.
`
`The GLP-2 formulation of claim 31, wherein the GLP-2 is [h[Gly2]GLP-2]
`
`h(Gly2}GLP-2.
`
`8
`
`