UNITED STATES PATENT AND TRADEMARK OFFICE
`
`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
`
`ART UNIT
`
`PAPER NUMBER
`
`1653
`
`DATE MAILED: 1010412004
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`PT0-90C (Rev. 10103)
`
`CFAD Exhibit 1015
`
`1
`
`

`

`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
`
`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
`
`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`4a) Of the above claim(s) __ is/are withdrawn from consideration.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
`
`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
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page2
`
`1.
`
`The finality of the previous Office Action dated June 8, 2004 is withdrawn due to a new
`
`DETAILED ACTION
`
`ground rejection.
`
`2.
`
`Claims 1-54 and 58-78 are pending.
`
`Status of the Claims
`
`Applicants' amendment filed September 07, 2004 is acknowledged. Applicants'
`
`response has been fully considered. Claims 25-29, 42, 49 and 59 have been amended, claims 56
`
`and 57 have been cancelled, and new claims 77 and 78 have been added. Therefore, claims 1-54
`
`and 58-78 are examined.
`
`Objection Withdrawn
`
`3.
`
`The previous objection of claims 56, 57 and 59 is withdrawn in view of applicants'
`
`cancellation of the claim, applicants' amendment to the claim, and applicants' response at pages
`
`13-14 in the amendment filed September 07, 2004.
`
`Rejection Withdrawn
`
`Claim Rejections -35USC§112
`
`4.
`
`The previous rejection of claims 2-4, 23-30, 34, 35, 37, 38, 41, 42, 44, 45, 47-54, 56, 57,
`
`63, 65-67 are rejected under 35 U.S.C. 112, second paragraph under 35 U.S.C. 112, second
`
`paragraph, as being indefinite, is withdrawn in view of applicants' cancellation of the claim,
`
`applicants' amendment to the claim, and applicants' response at pages 14-17 in the amendment
`
`filed September 07, 2004.
`
`Claim Rejections -35USC§112
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`3
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 3
`
`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.
`
`5.
`
`Claims 17 and 58-63 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.
`
`6.
`
`Claims 17 and 58, 60-63 are indefinite because of the use of the term "one or more
`
`substitutions, additions, deletions, or modifications". The cited term renders the claim indefinite,
`
`it is not clear where the substitutions, additions, deletions, or modifications occur ill the sequence
`
`and how many amino acids are substituted, added, deleted or modified, and what resulting
`
`sequence is.
`
`Claim 59 is indefinite as to the claim recites amino acid substitutions at various positions
`
`7.
`,
`without indicating "SEQ ID NO:" of the reference sequence, it is not clear what amino acid
`
`sequence these positions are referring to.
`
`In response, applicants indicate the amino acid sequence of GLP-2 was well known in the
`
`art prior to the earlier priority date of the application, and further cite many patents and
`
`references to indicate various vertebrate forms of GLP-2 include, for example, rat GLP-2 and
`
`its homologues including ox GLP-2, porcine GLP-2, degu GLP-2, bovine GLP-2, guinea pig
`
`GLP-2, hamster GLP-2, human GLP-2, rainbow trout GLP-2, and chicken GLP-2, the sequences
`
`of which have been reported by many authors, and the practice of those skilled in the art was to
`
`indicate amino acid substitutions in the GLP-2 sequence by reciting, for example, "Lys20GLP-2"
`
`where the amino acid substitution, followed by the position number in superscript, precedes the
`
`peptide indicator GLP-2. The disclosure of the instant application conforms to this practice and
`
`4
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page4
`
`describes GLP-2 as a 33 amino acid peptide (See e.g., page 6, lines 16-18 of the specification;
`
`pages 17-19 of the response).
`
`The response has been considered, however, the argument is not found persuasive
`
`because there are sequence variations among different naturally occurring vertebrate GLP-2
`
`peptides (see Fig. 2 of Buhl et al., J. Biol. Chem. 263, 8621-8624 (1988)) and synthetic GLP-2
`
`peptides (e.g., Lys20 Arg30GLP-2(1-33), Arg30Lys34GLP-2(1-35) in WO 99/43361, the reference
`
`has shown the parent sequence at page7), thus, it is not clear which amino acid sequence is used
`
`for the substitution, and what resulting sequence the GLP-2 analog has, if only the position of
`
`substitution and amino acid residue substituted are given without a reference sequence.
`
`Furthermore, it is noted that both U.S. Patents 5,789,379 and 5,834,428 have "SEQ ID NO:"
`
`cited in the claims when there is a variation indicated in the sequence.
`
`Claim Rejections -35USC§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.
`
`8.
`
`Claims 1-8, 10, 22, 49-55, 58, 63-71, 73 and 78 are rejected under 35 U.S.C. 103(a) as
`
`being unpatentable over Knudsen et al. (WO 99/43361) in view ofKomfelt et al. (U.S. Patent
`
`5,652,216, July 29, 1997).
`
`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
`
`5
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 5
`
`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 2-4 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 10; claim 22), GLP-2 derivative has an amino acid sequence of
`
`HGDGSFSDEMNTILDNLAARDFINWLIQTKITD (having the same sequence as h(Gly2)GLP-
`
`2) or its variants at several positions (page 7, lines 1-12; claims 58, 63-71, 73), and the
`
`pharmaceutical composition can be 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 and 78). However, Knudsen et al. do not disclose using histidine as a stabilizing agent.
`
`Komfelt et al. disclose using stabilizing amount of a pharmaceutically acceptable ampholyte
`
`such as glycine, histidine (5, 10 or 20 mM corresponding about 1.7, 3.4 or 6.8%) or GlyGly in a
`
`pharmaceutical preparation comprising glucagon (column 2, lines 21-45; Table 1; claims 1 and
`
`55). At the time the invention was made, it would have been obvious that a person of ordinary
`
`skill in the art is motivated to prepare a phamrnceutical composition of GLP-2 as indicated by
`
`Knudsen et al. with the addition of histidine as a stabilizing agent as taught by Komfelt et al.
`
`because stabilizing amount of histidine has been shown to stabilize glucagon in the formulation
`
`(Table 1; Fig. 1; >90% glucagons detected after 4 weeks at 60 °C), and GLP-2 is a glucagons like
`
`peptide. 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.
`
`6
`
`

`

`Application/Control Number: 09/750,_022
`Art Unit: 1653
`
`Page6
`
`9.
`
`Claims 11, 12, 74 and 75 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Knudsen et al. in view of Komfelt et al. as applied to claims 1-8 and 10 above, further in view of
`
`Hora et al. (U. S. Patent 5,997,856).
`
`The combined references of Knudsen et al. and Komfelt 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 Komfelt 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 that a person of ordinary skill in the art is motivated to prepare a phannaceutical
`
`formulation of GLP-2 analogs as indicated by Knudsen et al. and Komfelt et al. with a known
`
`concentration of mannitol taught by Hora et al. (claims 11, 12, 74 and 75) 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.
`
`10.
`
`Claims 13-15, 17-20 and 76 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over Knudsen et al. in view of Komfelt et al. as applied to claims 1-8 and 10 above, further in
`
`view of Drucker et al. (WO 97/39031).
`
`The combined references of Knudsen et al. and Komfelt et al. teach a phannaceutical
`
`composition comprising a GLP-2 derivative or analog, an isotonic agent such as mannitol, a
`
`7
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 7
`
`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 the source of GLP-2 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 that a person of ordinary skill in the art is motivated to prepare the pharmaceutical
`
`composition as indicated by Knudsen et al. and Komfelt et al. using the GLP-2 analogs taught by
`
`Drucker et al. (claims 13-15, 17-20 and 76) to treat a gastrointestinal disease because the use of
`
`DPP-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.
`
`11.
`
`Claims 16 and 21 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Knudsen et al. in view ofKomfelt et al. as applied to claims 1-8 and 10 above, further in view of
`
`Thim et al. (U.S. Patent 5,912,229).
`
`The combined references of Knudsen et al. and Komfelt 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 Komfelt et al. do not disclose the use of GLP-2 receptor to identify peptides
`
`that bind GLP-2receptor or as GLP-2 receptor antagonist. Thim et al. disclose a GLP-2 receptor
`
`8
`
`

`

`Application/Control Number: 091750,022
`Art Unit: 1653
`
`Page 8
`
`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 that a person of ordinary skill in the art is motivated to
`
`prepare the pharmaceutical composition as indicated by Knudsen et al. and Kornfelt et al.
`
`(claims 16 and 21) using the GLP-2 analogs taught by Thim et al. to treat a GLP-2 receptor-
`
`associated disease because the pharmaceutical composition containing the GLP-2 receptor
`
`antagonist is stabilized and useful in the treatment of 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.
`
`12.
`
`Claims 43-46 and 77 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Knudsen et al. in view of Kornfelt et al. as applied to claims 1-8 and 10 above, further in view of
`
`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
`
`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 that a person of ordinary
`
`skill in the art is motivated to prepare a kit as taught by Drucker (claims 43-46 and 77) using the
`
`pharmaceutical composition as indicated by Knudsen et al. and Kornfelt et al. to treat a
`
`gastrointestinal disease because the kit containing the stabilized pharmaceutical composition is
`
`9
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 9
`
`useful in the treatment of a gastrointestinal disease. 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.
`
`13.
`
`Claims 9, 23-30, 47, 48 and 72 are objected to as being dependent upon a rejected base
`
`claim, but would be allowable ifrewritten in independent form including all of the limitations of
`
`the base claim and any intervening claims.
`
`Co11clusion
`
`14.
`
`Claims 1-8, 10-22, 43-46, 49-55, 58, 59, 63-71and73-78 are rejected, and claims 9, 23-
`
`30, 47, 48 and 72 are objected to. It appears that claims 31-42 are free of prior art and allowable.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Chih-Min Kam whose telephone number is (571) 272-0948. 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, Jon Weber can be reached at 571-272-0925. The fax phone number for the
`
`organization where this application or proceeding is assigned is 703-872-9306.
`
`Information regarding the status of an application may be obtained from the Patent
`
`Application hlformation Retrieval (PAIR) system. Status information for published applications
`
`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
`
`applications is available through Private PAIR only. For more information about the PAIR
`
`system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
`
`system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
`
`10
`
`

`

`Application/Control Number: 09/750,022
`Art Unit: 1653
`
`Page 10
`
`Chih-Min Kam, Ph.D. Glt /:..
`Patent Examiner
`
`CMK
`September 25, 2004
`
`11
`
`