.,
`
`UNITED STATES PATENT AND ThADEMARK OFFICE
`
`UNITED STATES DEPARTMENT Qt' COMMERCE
`United State• Patent and Trademark Office
`Addn:o: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Vl!Binia 22313·1450
`www.uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`09/750,022
`
`1212912000
`
`I ndu J. Isaacs
`
`016777/0454
`
`6419
`
`09/1612003
`
`7590
`Stephen A. Bent
`FOLEY & LARDNER
`Washington Harbour
`3000 K Street, N.W., Suite 500
`Washington, DC 20007-5109
`
`EXAMINER
`
`KAM, CHIH MIN
`
`ART UNIT
`
`1653
`
`DA TE MAILED: 09/16/2003
`
`PAPER NUMBER
`
`lj
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`PT0-90C (Rev. 07-01)
`
`CFAD Exhibit 1011
`
`1
`
`

`

`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`09/750,022
`
`Examiner
`
`ISAACS, INDU J.
`
`Art Unit
`
`1653
`Chih-Min Kam
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE J MONTH(S) FROM
`THE MAILING DATE OF THIS COMMUNICATION.
`• Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If the period for reply specified above is less than thirty (30) days, a reply within the statutory minimum of thirty (30) days will be considered timely.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`- Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent tenn adjustment. See 37 CFR 1. 704(b ).
`Status
`·1 )[8] Responsive to communication(s) filed on 09 Julv 2003.
`
`-
`-
`
`2a)0 This action is FINAL.
`
`2b)[8] This action is non-final.
`
`3)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parle Quayle, 1935 C.D. 11, 453 O.G. 213.
`Disposition of Claims
`
`4)[8] Claim(s) 1-55 is/are pending in the application.
`
`4a) Of the above claim(s) __ is/are withdrawn from consideration.
`
`5)[8] Claim(s) 36.39 and 40 is/are allowed.
`
`6)[8] Claim(s) 1-35.37.38 and 41-55 is/are rejected.
`
`7)0 Claim(s) __ is/are objected to.
`
`8)0 Claim(s) __ are subject to restriction and/or election requirement.
`Application Papers
`
`9)0 The specification is objected to by the Examiner.
`
`10)0 The drawing(s) filed on __ is/are: a)D accepted or b)O objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`11 )0 The proposed drawing correction filed on __ is: a)O approved b )0 disapproved by the Examiner.
`
`If approved, corrected drawings are required in reply to this Office action.
`12)0 The oath or declaration is objected to by the Examiner.
`
`Priority under 35 U.S.C. §§ 119 and 120
`13)[8] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)[8] All b)O Some* c)O None of:
`
`1.[8] Certified copies of the priority documents have been received.
`
`2.0 Certified copies of the priority documents have been received in Application No. __ .
`
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`*See the attached detailed Office action for a list of the certified copies not received.
`14)0 Acknowledgment is made of a claim for domestic priority under 35 U.S.C. § 119(e) (to a provisional application).
`a) 0 The translation of the foreign language provisional application has been received.
`15)0 Acknowledgment is made of a claim for domestic priority under 35 U.S.C. §§ 120and/or121.
`Attachment(s)
`
`1) [8] Notice of References Cited (PT0-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PT0-948)
`3) 0 Information Disclosure Staten:ient(s) (PT0-1449) Paper No(s) __ .
`
`4) [8J Interview Summary (PT0-413) Paper No(s). 13.
`5) 0 Notice of Informal Patent Application (PT0-152)
`6) 0 Other:
`
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 04-01)
`
`Office Action Summary
`
`Part of Paper No. 13
`
`2
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 2
`
`DETAILED ACTION
`
`Status of the Claims
`
`1.
`
`Claims 1-55 are pending.
`
`Applicants' amendment filed July 9, 2003 (Paper No. 12) is acknowledged. Applicants'
`
`response has been fully considered. Claims 1, 14, 15 and 32 have been amended, and new claim
`
`55 has been added. Therefore, claims 1-55 are examined.
`
`Rejection Withdrawn
`
`Claim Rejections - 35 USC§ 103
`
`2.
`
`The previous rejection of claims 1-10, 22, and 49-54 under 35 U.S.C. 103(a) as being
`
`unpatentable over Knudsen et al. (WO 99/43361) in view of Makino et al. (U.S. Patent
`
`4,985,244), is withdrawn in view of applicants' response at pages 3-5 in Paper No. 12.
`
`3.
`
`The previous rejection of claims 11, 12 and 31under35 U.S.C. 103(a) as being
`
`unpatentable over Knudsen et al. in view of Makino et al. as applied to claims 1-10 above,
`
`further in view of Hora et al. (U. S. Patent 5,997,856), is withdrawn in view of applicants'
`
`response at page 5 in Paper No. 12.
`
`4.
`
`The previous rejection of claims 13-15 and 17-20 under 35 U.S.C. 103(a) as being
`
`unpatentable over Knudsen et al. in view of Makino et al. as applied to claim 1 above, further in
`
`view of Drucker et al. (WO 97 /39031 ), is withdrawn in view of applicants' response at page 6 in
`
`Paper No. 12.
`
`5.
`
`The previous rejection of claims 16 and 21under35 U.S.C. 103(a) as being unpatentable
`
`over Knudsen et al. in view of Makino et al. as applied to claim 1 above, further in view of Thim
`
`3
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 3
`
`et al. (U.S. Patent 5,912,229), is withdrawn in view of applicants' response at page 6 in Paper
`
`No. 12.
`
`6.
`
`The previous rejection of claims 43-46 under 35 U.S.C. 103(a) as being unpatentable
`
`over Knudsen et al. in view of Makino et al. as applied to claim 1 above, further in view of
`
`Drucker (U.S. Patent 5,952,301), is withdrawn in view of applicants' response at pages 6-7 in
`
`Paper No. 12.
`
`Claim Objections
`
`7.
`
`Claim 1 is objected to because the amended claim in the amendment filed July 9, 2003
`
`(Paper No. 12) is not based on the previously amended claim 1 filed November 27, 2002 (Paper
`
`No. 8).
`
`Claim Rejections - 35 USC§ 112
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the
`subject matter which the applicant regards as his invention.
`
`8.
`
`Claims 2-4, 17, 23-30, 34, 35, 37, 38, 41, 42, 44, 45 and 47-54 are rejected under 35
`
`U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and
`
`distinctly claim the subject matter which applicant regards as the invention.
`
`9.
`
`Claims 2-4, 34, 35, 37, 38, 44, 45, 50 and 51 are indefinite because of the use of the term
`
`"greater than about 6.0" or "greater than about 5.5''. The term "greater than about 6.0" or
`
`"greater than about 5.5'' renders the claim indefinite, it is unclear whether the pH of the
`
`formulation is greater than pH 6.0 (or 5.5), or less than pH 6.0 (5.5) as to "about". Claims 3, 4,
`
`35, 38, 45 and 51 are included in this rejection for being dependent on rejected claims and not
`
`correcting the deficiency of the claims from which they depend.
`
`4
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page4
`
`10.
`
`Claims 23-25, for example, are indefinite because of the use of the term "less than about
`
`5%", "for up to at least 6 months" or "less than about 3 to about 4%". The term "less than about
`
`5%'', "for up to at least 6 months" or "less than about 3 to about 4%" renders the claim
`
`indefinite, it is unclear whether the water content in the lyophilized formulation is less than 5%
`
`as to "less than", or greater than 5% as to "about'', whether the GLP-2 formulation is stable less
`
`than 6 months as to "up to" or greater than 6 months as to "about", and the percentage of
`
`degradation of GLP-2 is in the range of 3 to 4% as to "about. .. to about'', or less than 3% as to
`
`"less than''. See also claims 26-30, 41, 42 and 47.
`
`11.
`
`Claim 42 is indefinite because of the use of the term "no more than about 2%". The term
`
`"no more than about 2%" renders the claim indefinite, it is unclear whether the water content is
`
`less than 2% as to "no more than" or greater than 2% as to "about".
`
`12.
`
`Claim 48 is indefinite because of the use of the term "up to about 24 hours". The term
`
`"up to about 24 hours" renders the claim indefinite, it is unclear the GLP-2 formulation is stable
`
`less than 24 hours as to "up to", or more than 24 hours as to "about".
`
`13.
`
`Claim 17 is indefinite because of the use of the term "one or more amino acid
`
`substitutions, additions, deletions or modifications" or "biological activity". The term "one or
`
`more amino acid substitutions, additions, deletions or modifications" or "biological activity"
`
`renders the claim indefinite, it is unclear which amino acids are modified, and what amino acids
`
`are used for modifications, and what the biological activity l's.
`
`14.
`
`Claims 49-54 are indefinite because of the use of the term "a disorder, disease or
`
`condition" or "gastrointestinal disease". The term "a disorder, disease or condition" or
`
`"gastrointestinal disease" renders the claim indefinite, it is unclear what disease is being treated.
`
`5
`
`

`

`,
`
`Application/Control Nwnber: 09/750,022
`Art Unit: 1653
`
`Page 5
`
`Claims 50-54 are included in this rejection for being dependent on rejected claims and not
`
`correcting the deficiency of the claims from which they depend.
`
`15.
`
`Claims 49-54 are indefinite because the claims lack essential steps in the method of
`
`treating a hwnan or an animal having a disease using the GLP-2 formulation. The omitted step is
`
`the outcome for the treatment. Claims 50-54 are included in this rejection for being dependent
`
`on a rejected claim and not correcting the deficiency of the claim from which they depend.
`
`Claim Rejections - 35 USC§ 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness
`
`rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in
`section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are
`such that the subject matter as a whole would have been obvious at the time the invention was made to a person
`having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the
`manner in which the invention was made.
`
`16.
`
`Claims 1-10, 22, and 49-55 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over Knudsen et al. (WO 99/43361) in view of Yamazaki et al. (U.S. Patent 6,120,761, 102(e)
`
`date, December 16, 1998).
`
`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
`
`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
`
`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
`
`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
`
`buffer is used (page 4, line 19-29; page 3, lines 24-25; claims 1-4 and 10). The reference also
`
`indicates the concentration of the GLP-2 derivative is more than 0.5 mg and less than 100 mg/ml
`
`(page 4, lines 9-12; page 13, lines 16-19; claims 5-8), the formulation can be obtained in
`
`lyophilized form (page 13, line 1 O; claim 22), and the pharmaceutical composition can be
`
`6
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 6
`
`administered by injection or means of infusion pump to treat small bowl syndrome or intestinal
`
`inflammation (page 12, lines 13-16; page 13, 16-24, claims 49-54). However, Knudsen et al. do
`
`not disclose using histidine as a stabilizing agent. Yamazaki et al. disclose using 1-10 mg/ml of
`
`histidine (corresponding to 0.1-1 %, w/v%) as a stabilizing agent in an erythropoietin solution
`
`preparation (column 1, lines 53-60; column 2, lines 47-58; column 3, lines 6-9; Fig. 3; Tables 4
`
`and 5; claims 9 and 55). At the time the invention was made, it would have been obvious to a
`
`person of ordinary skill in the art to prepare a pharmaceutical composition of GLP-2 as indicated
`
`by Knudsen et al. with the addition of histidine as a stabilizing agent as taught by Yamazaki et
`
`al. to treat a gastrointestinal disease because using histidine as a stabilizing agent is safe without
`
`the risk of viral contamination and is also economically advantageous than using the
`
`conventional stabilizer (column 4, lines 38-51). Thus, the combined references result in the
`
`claimed invention and was, as a whole, prima facie obvious at the time the claimed invention
`
`was made.
`
`17.
`
`Claims 11, 12, 31and33 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Knudsen et al. in view of Yamazaki et al. as applied to claims 1-10 above, further in view of
`
`Hora et al. (U.S. Patent 5,997,856).
`
`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
`
`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
`
`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
`
`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
`
`buffer is used (page 4, line 19-29; page 3, lines 24-25; claims 1-4 and 10), the concentration of
`
`the GLP-2 derivative is more than 0.5 mg and less than 100 mg/ml (page 4, lines 9-12; page 13,
`
`7
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 7
`
`lines 16-19; claims 5-8), the formulation can be obtained in lyophilized form (page 13, line 10),
`
`and Yamazaki et al. disclose using 1-10 mg/ml of histidine (corresponding to 0.1-1 %, w/v%) as
`
`a stabilizing agent in an erythropoietin solution preparation (column 1, lines 53-60; column 2,
`
`lines 47-58; column 3, lines 6-9; Fig. 3; Tables 4 and 5; claim 9). However, Knudsen et al. and
`
`Yamazaki et al. do not disclose the concentration of mannitol in the pharmaceutical composition.
`
`Hora et al. disclose 1-5% mannitol is used as a bulking agent in a protein preparation (column
`
`25, lines 7-14). At the time the invention was made, it would have been obvious to a person of
`
`ordinary skill in the art using the pharmaceutical formulation of GLP-2 analogs as indicated by
`
`Knudsen et al. and Yamazaki et al. with a known concentration of mannitol taught by Hora et al.
`
`(claims 11, 12, 31 and 33) to treat a gastrointestinal disease because the addition of a known
`
`concentration of mannitol can further improve the stability of the pharmaceutical composition.
`
`Thus, the combined references result in the claimed invention and was, as a whole, prima facie
`
`obvious at the time the claimed invention was made.
`
`18.
`
`Claims 13-15, 17-20 and 32 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over Knudsen et al. in view of Yamazaki et al. and Hora et al. as applied to claim 1 above,
`
`further in view of Drucker et al. (WO 97/39031).
`
`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
`
`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
`
`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
`
`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
`
`buffer is used (page 4, line 19-29; page 3, lines 24-25; claim 1); Yamazaki et al. disclose using
`
`histidine as a stabilizing agent in a an erythropoietin solution preparation composition (column 1,
`
`8
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 8
`
`lines 53-60; column 2, lines 47-58; column 3, lines 6-9; Fig. 3; Tables 4 and 5) and Hora et al.
`
`disclose 1-5% mannitol is used as a bulking agent in a protein preparation (column 25, lines 7-
`
`14). However, Knudsen et al., Yamazaki et al. and Hora et al. do not disclose the source and the
`
`sequences ofGLP-2, the h[Gly2]GLP-2 analog, and DPP-IV-resistant GLP-2 analogs. Drucker
`
`et al. disclose the sequence of human GLP-2, h[Gly2]GLP-2 analog, and DPP-IV-resistant GLP-
`
`2 analogs, where the Ala at position 2 has been modified (page 7, lines 8-20; page 9, lines 11-22,
`
`Table 1 ). At the time the invention was made, it would have been obvious to a person of
`
`ordinary skill in the art using the GLP-2 analogs taught by Drucker et al. to prepare the
`
`pharmaceutical composition as indicated by Knudsen et al., Yamazaki et al. and Hora et al.
`
`(claims 13-15, 17-20 and 32) to treat a gastrointestinal disease because the use ofDPP-IV
`
`resistant GLP-2 analogs in the pharmaceutical composition would result in a more stable
`
`pharmaceutical composition in vivo, where the GLP-2 analogs are degraded more slowly in vivo
`
`condition. Thus, the combined references result in the claimed invention and was, as a whole,
`
`prima facie obvious at the time the claimed invention was made.
`
`19.
`
`Claims 16 and 21 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Knudsen et al. in view of Yamazaki et al. as applied to claim 1 above, further in view of Thim et
`
`al. (U.S. Patent 5,912,229).
`
`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
`
`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
`
`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
`
`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
`
`buffer is used (page 4, line 19-29; page 3, lines 24-25; claim 1), and Yamazaki et al. disclose .
`
`9
`
`

`

`,
`
`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 9
`
`using histidine as a stabilizing agent in a an erythropoietin solution preparation composition
`
`(column 1, lines 53-60; column 2, lines 47-58; column 3, lines 6-9; Fig. 3; Tables 4 and 5).
`
`However, Knudsen et al. and Yamazaki et al. do not disclose the use of GLP-2 receptor to
`
`identify peptides that bind GLP-2 receptor or as GLP-2 receptor antagonist. Thim et al. disclose
`
`a GLP-2 receptor is identified and cloned, and a cell line stably expressing the receptor is used in
`
`a screening assay to identify the antagonist of GLP-2 receptor (column 10, lines 43-59). At the
`
`time the invention was made, it would have been obvious to a person of ordinary skill in the art
`
`using the GLP-2 analogs taught by Thim et al. to prepare the pharmaceutical ~omposition as
`
`indicated by Knudsen et al. and Yamazaki et al. (claims 16 and 21) to treat a GLP-2 receptor-
`
`associated disease because the GLP-2 receptor antagonist can be used to treat GLP-2 receptor-
`
`associated diseases. Thus, the combined references result in the claimed invention and was, as a
`
`whole, prima facie obvious at the time the claimed invention was made.
`
`20.
`
`Claims 43-46 are rejected under 35 U.S.C. 103(a) as being unpatentable over Knudsen et
`
`al. in view of Yamazaki et al. as applied to claim 1 above, further in view of Drucker (U.S.
`
`Patent 5,952,301).
`
`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
`
`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
`
`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
`
`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
`
`buffer is used (page 4, line 19-29; page 3, lines 24-25; claim 1), and Yamazaki et al. disclose
`
`using histidine as a stabilizing agent in a an erythropoietin solution preparation composition
`
`(column 1, lines 53-60; column 2, lines 47-58; column 3, lines 6-9; Fig. 3; Tables 4 and 5).
`
`10
`
`

`

`,
`
`Application/Control Number: 091750,022
`Art Unit: 1653
`
`Page 10
`
`However, Knudsen et al. and Yamazaki et al. do not disclose a kit comprising a lyoph1lized
`
`GLP-2 formulation. Drucker disclose a kit comprising GLP-2 or GLP-2 analogs (column 2, lines
`
`56-61). At the time the invention was made, it would have been obvious to a person of ordinary
`
`skill in the art using the pharmaceutical composition as indicated by Knudsen et al .. and
`
`Yamazaki et al. to prepare a kit as taught by Drucker (claims 43-46) to treat a gastrointestinal
`
`disease because the kit containing the pharmaceutical composition can be used more
`
`conveniently in the treatment. Thus, the combined references result in the claimed invention and
`
`was, as a whole, prima facie obvious at the time the claimed invention was made.
`
`Conclusion
`
`21.
`
`Claims 1-35, 37, 38 and 41-55 are rejected. It appears that claims 36, 39 and 40 are free
`
`· of prior art.
`
`A telephone call was made to Attorney, Michele Simkin on September 15, 2003
`
`regarding the allowable subject matter (see Interview Summary), however, applicants indicate
`
`they want to review the Office Action before making any decision.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Chih-Min Karn whose telephone number is (703) 308-9437. The
`
`examiner can normally be reached on 8.00-4:30, Mon-Fri.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Christopher Low can be r~ached on (703) 308-2923. The fax phone numbers for the
`
`organization where this application or proceeding is assigned are (703) 308-0294 for regular
`
`communications and (703) 308-4227 for After Final communications.
`
`11
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`

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`,
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`Application/Control Number: 091750,022
`Art Unit: 1653
`
`Page 11
`
`Any inquiry of a general nature or relating to the status of this application or proceeding
`
`should be directed to the receptionist whose telephone number is (703) 308-0196.
`
`Chih-Min Kam, Ph. D. Crl t:-(cid:173)
`Patent Examiner
`
`September 13, 2003
`
`. t/uiJpW/Jw
`
`ClffllSlOPHER S. F. LOW
`IUP'ERYISORY PATENT ElAM1111ER
`TlCHNOt.OGY CENTER tlOO
`
`12
`
`