`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address· COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`09/750,022
`
`1212912000
`
`I ndu J. Isaacs
`
`016777/0454
`
`6419
`
`10/04/2004
`
`7590
`Stephen A Bent
`FOLEY & LARDNER
`Washington Harbour
`3000 K Street, N.W., Suite 500
`Washington, DC 20007-5109
`
`EXAMINER
`
`KAM, CHIH MIN
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`ART UNIT
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`PAPER NUMBER
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`1653
`
`DATE MAILED: 1010412004
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`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`PT0-90C (Rev. 10103)
`
`CFAD Exhibit 1015
`
`1
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`
`
`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`09/750,022
`
`Examiner
`
`ISAACS, INDU J.
`
`Art Unit
`
`-------= The.MAIL/NG DA TE of this communication appears on the cover sheet with the correspondence address -(cid:173)
`
`Chih-Min Kam
`
`1653
`
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE;}. 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 term adjustment See 37 CFR 1.704(b).
`
`Status
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`1 )[8J Responsive to communication(s) filed on 07 September 2004.
`2a)0 This action is FINAL.
`2b)[8J 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
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`4 )[8J Claim(s) 1-54 and 58-78 is/are pending in the application.
`4a) Of the above claim(s) __ is/are withdrawn from consideration.
`5)l'SJ Claim(s) 31-42 is/are allowed.
`6)[8J Claim(s) 1-8. 10-22.43-46.49-55.58.59.63-71 and 73-78 is/are rejected.
`7)[8J Claim(s) 9.23-30.47.48 and 72 is/are objected to.
`8)0 Claim(s) __ are subject to restriction and/or election requirement.
`
`Application Papers
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`9)0 The specification is objected to by the Examiner.
`10)0 The drawing(s) filed on __ is/are: a)O 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).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`11 )0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PT0-152.
`
`Priority under 35 U.S.C. § 119
`
`12)[8;] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)[8J All b)O Some* c)O None of:
`1.[8J 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.
`
`Attachment(s)
`1) [8J Notice of References Cited (PT0-892)
`4) [SJ Interview Summary (PT0-413)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PT0-948)
`Paper No(s)/Mail Date. 0704.
`5) 0 Notice of Informal Patent Application (PT0-152)
`3) 0 Information Disclosure Statement(s) (PT0-1449 or PTO/SB/08)
`6) 0 Other: __ .
`Paper No(s)/Mail Date __ .
`U~.S~.P,Pa~te~nt~an~dTTr~a;d~ema;;;;;;:;:rk~O~ffic~e~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~-~~~..........1
`PTOL-326 (Rev. 1-04)
`Office Action Summary
`
`Part of Paper No./Mail Date 2004-0925
`
`2
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`
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page2
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`1.
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`The finality of the previous Office Action dated June 8, 2004 is withdrawn due to a new
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`DETAILED ACTION
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`ground rejection.
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`2.
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`Claims 1-54 and 58-78 are pending.
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`Status of the Claims
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`Applicants' amendment filed September 07, 2004 is acknowledged. Applicants'
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`response has been fully considered. Claims 25-29, 42, 49 and 59 have been amended, claims 56
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`and 57 have been cancelled, and new claims 77 and 78 have been added. Therefore, claims 1-54
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`and 58-78 are examined.
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`Objection Withdrawn
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`3.
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`The previous objection of claims 56, 57 and 59 is withdrawn in view of applicants'
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`cancellation of the claim, applicants' amendment to the claim, and applicants' response at pages
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`13-14 in the amendment filed September 07, 2004.
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`Rejection Withdrawn
`
`Claim Rejections -35USC§112
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`4.
`
`The previous rejection of claims 2-4, 23-30, 34, 35, 37, 38, 41, 42, 44, 45, 47-54, 56, 57,
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`63, 65-67 are rejected under 35 U.S.C. 112, second paragraph under 35 U.S.C. 112, second
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`paragraph, as being indefinite, is withdrawn in view of applicants' cancellation of the claim,
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`applicants' amendment to the claim, and applicants' response at pages 14-17 in the amendment
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`filed September 07, 2004.
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`Claim Rejections -35USC§112
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`The following is a quotation of the second paragraph of 35 U.S.C. 112:
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`3
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`
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page 3
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`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.
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`5.
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`Claims 17 and 58-63 are rejected under 35 U.S.C. 112, second paragraph, as being
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`indefinite for failing to particularly point out and distinctly claim the subject matter which
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`applicant regards as the invention.
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`6.
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`Claims 17 and 58, 60-63 are indefinite because of the use of the term "one or more
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`substitutions, additions, deletions, or modifications". The cited term renders the claim indefinite,
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`it is not clear where the substitutions, additions, deletions, or modifications occur ill the sequence
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`and how many amino acids are substituted, added, deleted or modified, and what resulting
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`sequence is.
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`Claim 59 is indefinite as to the claim recites amino acid substitutions at various positions
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`7.
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`without indicating "SEQ ID NO:" of the reference sequence, it is not clear what amino acid
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`sequence these positions are referring to.
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`In response, applicants indicate the amino acid sequence of GLP-2 was well known in the
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`art prior to the earlier priority date of the application, and further cite many patents and
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`references to indicate various vertebrate forms of GLP-2 include, for example, rat GLP-2 and
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`its homologues including ox GLP-2, porcine GLP-2, degu GLP-2, bovine GLP-2, guinea pig
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`GLP-2, hamster GLP-2, human GLP-2, rainbow trout GLP-2, and chicken GLP-2, the sequences
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`of which have been reported by many authors, and the practice of those skilled in the art was to
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`indicate amino acid substitutions in the GLP-2 sequence by reciting, for example, "Lys20GLP-2"
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`where the amino acid substitution, followed by the position number in superscript, precedes the
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`peptide indicator GLP-2. The disclosure of the instant application conforms to this practice and
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`4
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page4
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`describes GLP-2 as a 33 amino acid peptide (See e.g., page 6, lines 16-18 of the specification;
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`pages 17-19 of the response).
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`The response has been considered, however, the argument is not found persuasive
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`because there are sequence variations among different naturally occurring vertebrate GLP-2
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`peptides (see Fig. 2 of Buhl et al., J. Biol. Chem. 263, 8621-8624 (1988)) and synthetic GLP-2
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`peptides (e.g., Lys20 Arg30GLP-2(1-33), Arg30Lys34GLP-2(1-35) in WO 99/43361, the reference
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`has shown the parent sequence at page7), thus, it is not clear which amino acid sequence is used
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`for the substitution, and what resulting sequence the GLP-2 analog has, if only the position of
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`substitution and amino acid residue substituted are given without a reference sequence.
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`Furthermore, it is noted that both U.S. Patents 5,789,379 and 5,834,428 have "SEQ ID NO:"
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`cited in the claims when there is a variation indicated in the sequence.
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`Claim Rejections -35USC§103
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`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness
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`rejections set forth in this Office action:
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`(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.
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`8.
`
`Claims 1-8, 10, 22, 49-55, 58, 63-71, 73 and 78 are rejected under 35 U.S.C. 103(a) as
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`being unpatentable over Knudsen et al. (WO 99/43361) in view ofKomfelt et al. (U.S. Patent
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`5,652,216, July 29, 1997).
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`Knudsen et al. teach a pharmaceutical composition comprising a GLP-2 derivative or
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`analog, an isotonic agent such as mannitol, a buffer of histidine or sodium phosphate, a
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`pharmaceutical acceptable carrier, a preservative and a surfactant, where the solubility and
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`5
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page 5
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`stability of GLP-2 is improved and the pharmaceutical formulation has pH 6.9 if phosphate
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`buffer is used (page 4, line 19-29; page 3, lines 24-25; claims 2-4 and 10). The reference also
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`indicates the concentration of the GLP-2 derivative is more than 0.5 mg and less than 100 mg/ml
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`(page 4, lines 9-12; page 13, lines 16-19; claims 5-8), the formulation can be obtained in
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`lyophilized form (page 13, line 10; claim 22), GLP-2 derivative has an amino acid sequence of
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`HGDGSFSDEMNTILDNLAARDFINWLIQTKITD (having the same sequence as h(Gly2)GLP-
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`2) or its variants at several positions (page 7, lines 1-12; claims 58, 63-71, 73), and the
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`pharmaceutical composition can be administered by injection or means of infusion pump to treat
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`small bowl syndrome or intestinal inflammation (page 12, lines 13-16; page 13, 16-24, claims
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`49-54 and 78). However, Knudsen et al. do not disclose using histidine as a stabilizing agent.
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`Komfelt et al. disclose using stabilizing amount of a pharmaceutically acceptable ampholyte
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`such as glycine, histidine (5, 10 or 20 mM corresponding about 1.7, 3.4 or 6.8%) or GlyGly in a
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`pharmaceutical preparation comprising glucagon (column 2, lines 21-45; Table 1; claims 1 and
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`55). At the time the invention was made, it would have been obvious that a person of ordinary
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`skill in the art is motivated to prepare a phamrnceutical composition of GLP-2 as indicated by
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`Knudsen et al. with the addition of histidine as a stabilizing agent as taught by Komfelt et al.
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`because stabilizing amount of histidine has been shown to stabilize glucagon in the formulation
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`(Table 1; Fig. 1; >90% glucagons detected after 4 weeks at 60 °C), and GLP-2 is a glucagons like
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`peptide. Thus, the combined references result in the claimed invention and was, as a whole,
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`prima facie obvious at the time the claimed invention was made.
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`6
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`Application/Control Number: 09/750,_022
`Art Unit: 1653
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`Page6
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`9.
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`Claims 11, 12, 74 and 75 are rejected under 35 U.S.C. 103(a) as being unpatentable over
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`Knudsen et al. in view of Komfelt et al. as applied to claims 1-8 and 10 above, further in view of
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`Hora et al. (U. S. Patent 5,997,856).
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`The combined references of Knudsen et al. and Komfelt et al. teach a pharmaceutical
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`composition comprising a GLP-2 derivative or analog, an isotonic agent such as mannitol, a
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`buffer of sodium phosphate, a stabilizing agent of histidine, a pharmaceutical acceptable carrier,
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`a preservative and a surfactant as shown in the section above (see paragraph 8). However,
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`Knudsen et al. and Komfelt et al. do not disclose the concentration of mannitol in the
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`pharmaceutical composition. Hora et al. disclose 1-5% mannitol is used as a bulking agent in a
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`protein preparation (column 25, lines 7-14). At the time the invention was made, it would have
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`been obvious that a person of ordinary skill in the art is motivated to prepare a phannaceutical
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`formulation of GLP-2 analogs as indicated by Knudsen et al. and Komfelt et al. with a known
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`concentration of mannitol taught by Hora et al. (claims 11, 12, 74 and 75) to treat a
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`gastrointestinal disease because the addition of a known concentration of mannitol can further
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`improve the stability of the pharmaceutical composition. Thus, the combined references result in
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`the claimed invention and was, as a whole, prima facie obvious at the time the claimed invention
`
`was made.
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`10.
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`Claims 13-15, 17-20 and 76 are rejected under 35 U.S.C. 103(a) as being unpatentable
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`over Knudsen et al. in view of Komfelt et al. as applied to claims 1-8 and 10 above, further in
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`view of Drucker et al. (WO 97/39031).
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`The combined references of Knudsen et al. and Komfelt et al. teach a phannaceutical
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`composition comprising a GLP-2 derivative or analog, an isotonic agent such as mannitol, a
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`7
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page 7
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`buffer of sodium phosphate, a stabilizing agent of histidine, a pharmaceutical acceptable carrier,
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`a preservative and a surfactant as shown in the section above (see paragraph 8). However,
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`Knudsen et al. and Kornfelt et al. do not disclose the source of GLP-2 and DPP-IV-resistant
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`GLP-2 analogs. Drucker et al. disclose the sequence of human GLP-2, h[Gly2]GLP-2 analog,
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`and DPP-IV-resistant GLP-2 analogs, where the Ala at position 2 has been modified (page 7,
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`lines 8-20; page 9, lines 11-22, Table 1 ). At the time the invention was made, it would have
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`been obvious that a person of ordinary skill in the art is motivated to prepare the pharmaceutical
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`composition as indicated by Knudsen et al. and Komfelt et al. using the GLP-2 analogs taught by
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`Drucker et al. (claims 13-15, 17-20 and 76) to treat a gastrointestinal disease because the use of
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`DPP-IV resistant GLP-2 analogs in the pharmaceutical composition would result in a more stable
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`pharmaceutical composition in vivo, where the GLP-2 analogs are degraded more slowly in vivo
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`condition. Thus, the combined references result in the claimed invention and was, as a whole,
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`prima facie obvious at the time the claimed invention was made.
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`11.
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`Claims 16 and 21 are rejected under 35 U.S.C. 103(a) as being unpatentable over
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`Knudsen et al. in view ofKomfelt et al. as applied to claims 1-8 and 10 above, further in view of
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`Thim et al. (U.S. Patent 5,912,229).
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`The combined references of Knudsen et al. and Komfelt et al. teach a pharmaceutical
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`composition comprising a GLP-2 derivative or analog, an isotonic agent such as mannitol, a
`
`buffer of sodium phosphate, a stabilizing agent of histidine, a pharmaceutical acceptable carrier,
`
`a preservative and a surfactant as shown in the section above (see paragraph 8). However,
`
`Knudsen et al. and Komfelt et al. do not disclose the use of GLP-2 receptor to identify peptides
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`that bind GLP-2receptor or as GLP-2 receptor antagonist. Thim et al. disclose a GLP-2 receptor
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`8
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`Application/Control Number: 091750,022
`Art Unit: 1653
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`Page 8
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`is identified and cloned, and a cell line stably expressing the receptor is used in a screening assay
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`to identify the antagonist of GLP-2 receptor (column 10, lines 43-59). At the time the invention
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`was made, it would have been obvious that a person of ordinary skill in the art is motivated to
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`prepare the pharmaceutical composition as indicated by Knudsen et al. and Kornfelt et al.
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`(claims 16 and 21) using the GLP-2 analogs taught by Thim et al. to treat a GLP-2 receptor-
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`associated disease because the pharmaceutical composition containing the GLP-2 receptor
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`antagonist is stabilized and useful in the treatment of GLP-2 receptor-associated diseases. Thus,
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`the combined references result in the claimed invention and was, as a whole, prima facie obvious
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`at the time the claimed invention was made.
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`12.
`
`Claims 43-46 and 77 are rejected under 35 U.S.C. 103(a) as being unpatentable over
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`Knudsen et al. in view of Kornfelt et al. as applied to claims 1-8 and 10 above, further in view of
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`Drucker (U.S. Patent 5,952,301).
`
`The combined references of Knudsen et al. and Kornfelt et al. teach a pharmaceutical
`
`composition comprising a GLP-2 derivative or analog, an isotonic agent such as mannitol, a
`
`buffer of sodium phosphate, a stabilizing agent of histidine, a pharmaceutical acceptable carrier,
`
`a preservative and a surfactant as shown in the section above (see paragraph 8). However,
`
`Knudsen et al. and Kornfelt et al. do not disclose a kit comprising a lyophilized GLP-2
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`formulation. Drucker disclose a kit comprising GLP-2 or GLP-2 analogs (column 2, lines 56-
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`61). At the time the invention was made, it would have been obvious that a person of ordinary
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`skill in the art is motivated to prepare a kit as taught by Drucker (claims 43-46 and 77) using the
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`pharmaceutical composition as indicated by Knudsen et al. and Kornfelt et al. to treat a
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`gastrointestinal disease because the kit containing the stabilized pharmaceutical composition is
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`9
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page 9
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`useful in the treatment of a gastrointestinal disease. Thus, the combined references result in the
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`claimed invention and was, as a whole, prima facie obvious at the time the claimed invention
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`was made.
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`13.
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`Claims 9, 23-30, 47, 48 and 72 are objected to as being dependent upon a rejected base
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`claim, but would be allowable ifrewritten in independent form including all of the limitations of
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`the base claim and any intervening claims.
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`Co11clusion
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`14.
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`Claims 1-8, 10-22, 43-46, 49-55, 58, 59, 63-71and73-78 are rejected, and claims 9, 23-
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`30, 47, 48 and 72 are objected to. It appears that claims 31-42 are free of prior art and allowable.
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to Chih-Min Kam whose telephone number is (571) 272-0948. The
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`examiner can normally .be reached on 8.00-4:30, Mon-Fri.
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
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`supervisor, Jon Weber can be reached at 571-272-0925. The fax phone number for the
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`organization where this application or proceeding is assigned is 703-872-9306.
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`Information regarding the status of an application may be obtained from the Patent
`
`Application hlformation Retrieval (PAIR) system. Status information for published applications
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`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
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`applications is available through Private PAIR only. For more information about the PAIR
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`system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
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`system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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`10
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`Application/Control Number: 09/750,022
`Art Unit: 1653
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`Page 10
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`Chih-Min Kam, Ph.D. Glt /:..
`Patent Examiner
`
`CMK
`September 25, 2004
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`11