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 2231371450
`www.uspto.gov
`
`16/249,275
`
`01/16/2019
`
`Michael Soeberdt
`
`47TER10003VA
`
`9044
`
`DINSMORE & SHOHL LLP
`
`900 WILSHIRE DRIVE
`SUITE 300
`4404 444444044
`
`GARYU~ LIANKO G
`
`1658
`
`4444444444444
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`03/18/2020
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
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`following e—mail address(es):
`
`MichiganPatTM@dinsmore.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`017/09 A0170” Summary
`
`Application No.
`16/249,275
`Examiner
`Lianko G Garyu
`
`Applicant(s)
`Soeberdt et al.
`Art Unit
`1658
`
`AIA (FITF) Status
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTHS 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.
`|f 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). Responsive to communication(s) filed on 19 December 2019.
`El A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a). This action is FINAL.
`
`2b) D This action is non-final.
`
`3)[:] An election was made by the applicant in response to a restriction requirement set forth during the interview
`on
`; the restriction requirement and election have been incorporated into this action.
`
`4):] 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 Expade Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)
`
`Claim(s) fl is/are pending in the application.
`
`5a) Of the above Claim(s)
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`is/are withdrawn from consideration.
`
`
`
`[:1 Claim(ss)
`
`is/are allowed.
`
`8)
`Claim(s 114Is/are rejected
`
`D Claim(ss_) is/are objected to.
`
`) ) ) )
`
`S)
`are subject to restriction and/or election requirement
`[:1 Claim(s
`* If any claims have been determined aflowable. you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`
`http://www.uspto.gov/patents/init events/pph/index.jsp or send an inquiry to PPeredback@uspto.gov.
`
`Application Papers
`
`10)|:l The specification is objected to by the Examiner.
`
`is/are: a)[] accepted or b)l:] objected to by the Examiner.
`11)[:] The drawing(s) filed on
`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).
`
`Priority under 35 U.S.C. § 119
`
`12)D Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a)I:l All
`
`b)|:] Some**
`
`c)l:i None of the:
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`1C] Certified copies of the priority documents have been received.
`
`2C] Certified copies of the priority documents have been received in Application No.
`
`3D 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)
`
`Notice of References Cited (PTO-892)
`
`2) C] Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date_
`U.S. Patent and Trademark Office
`
`3) E] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
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`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20200312
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 2
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`DETAILED ACTION
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`Notice of Pre-AIA or AIA Status
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`The present application,
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`filed on or after March 16, 2013, is being examined
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`under the first inventor to file provisions of the AIA.
`
`Status of Claim
`
`Claims 1-14 are pending and under examination.
`
`Claim Rejections - 35 USC § 112
`
`Response to Arguments
`
`The rejection of claim 8, 9 and 11- 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112
`
`(pre-AIA), second paragraph has been withdrawn as necessitated by amendment.
`
`Claim Rejections - 35 USC § 103
`
`In the event the determination of the status of the application as subject to AIA
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`35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect,
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`any correction of the statutory basis for the rejection will not be considered a new
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`ground of rejection if the prior art relied upon, and the rationale supporting the
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`rejection, would be the same under either status.
`
`The following is a quotation of 35 U.S.C. 103 which forms the basis for all
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`obviousness rejections set forth in this Office action:
`
`A patent for a claimed invention may not be obtained, notwithstanding that the claimed
`invention is not identically disclosed as set forth in section 102, ifthe differences between the
`claimed invention and the prior art are such that the claimed invention as a whole would have
`been obvious before the effective filing date of the claimed invention to a person having
`ordinary skill
`in the art to which the claimed invention pertains. Patentability shall not be
`negated bythe manner in which the invention was made.
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 3
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`This application currently names joint inventors. In considering patentability of
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`the claims the examiner presumes that the subject matter of the various claims was
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`commonly owned as of the effective filing date of the claimed invention(s) absent any
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`evidence to the contrary. Applicant
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`is advised of the obligation under 37 CFR 1.56 to
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`point out the inventor and effective filing dates of each claim that was not commonly
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`owned as of the effective filing date of the later invention in order for the examiner to
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`consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2)
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`prior art against the later invention.
`
`The factual inquiries set forth in Graham v. John Deere C0., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied for establishing a background for determining
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`obviousness under 35 U.S.C. 103 are summarized as follows:
`
`1. Determining the scope and contents of the prior art.
`
`2. Ascertaining the differences between the prior art and the claims at issue.
`
`3. Resolving the level of ordinary skill
`
`in the pertinent art.
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`4. Considering objective evidence present in the application indicating
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`obviousness or nonobviousness.
`
`The rejection basis is maintained.
`
`Claims 1-12 and 14 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Ferreira et al. (US 5,389,615; 1995) and Brzoska et al. (“a-
`
`Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry,
`
`Antiinflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for
`
`the Treatment of Immune-Mediated Inflammatory Diseases", Endocrine Reviews, 2007;
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 4
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`pp. 581-602) in view of Zomaro (US 5,718,882; 1998), Gentilucci et al. (“Chemical
`
`Modifications Designed to Improve Peptide Stability:
`
`Incorporation of Non-Natural
`
`Amino Acids, Pseudo-Peptide Bonds, and Cyclization”, Current Pharmaceutical Design,
`
`2010, pp. 3185-3203; cited in the IDS), Chatterjee et al. (N-Methylation of Peptides: A
`
`New Perspective in Medicinal Chemistry”, Accounts of Chemical Research, 2008, pp.
`
`1331-1342), and The National Center for Biotechnology Information (“6-Amino-2—
`
`(dimethylamino)hexanoic acid" (2007); “N-Methyl—L—valine" (2005) and “N-Methyl—L—
`
`threonine" (2006)).
`
`Ferreira et al. teach the tripeptides Lys-Pro-Thr, Lys-D-Pro-Thr, Lys-Pro-Val and
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`Lys-D-Pro-Val (see col.
`
`lines 46-48), medicaments comprising the tripeptides and
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`methods of treating pain with the tripeptides thereof (see e.g., the abstract; col. 1, lines
`
`30-51; col. 3, line 53-col. 5, line 3). Brzoska et al. teach the tripeptides are anti-
`
`inflammatory peptides (see e.g., Table 6, §8. oc-MSH in experimentally induced acute
`
`pancreatitis sand §IV. Anti-inflammatory Effects of oc-MSH-Related Tripeptides Ih Vitro
`
`and I)?
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`I/Ii/o) and further suggest administering the tripeptides to treat immune-
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`mediated inflammatory diseases, e.g., pancreatitis, eczema (inflammatory disease of
`
`the skin), allergic asthma, rheumatoid arthritis (inflammatory disease of the joints), and
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`inflammatory bowel disease because of the activity of the KPV tripeptide is very similar
`
`to oc-MSH (see p. 596, right co|.-1St para.-p. 597, right col. continuing paragraph).
`
`The difference between the tripeptides of Ferreira et al. and Brzoska et al. and
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`the peptides of claims 1-12 and 14 is the methylation of the N- and C-termini amino
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`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 5
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`acids (i.e., N“,N0°,dimethyl-lysine and/or the C-terminal Na-methyl-Thr-OH, Na-methyl-
`
`Val-OH of Na-methyl-Thr-NHz).
`
`Zomaro teaches that an increase in resistance to protease degradation in
`
`peptides can be accomplished with the substitution of the terminal amino acids with
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`amino acids having unnatural chirality, such as methylated amino acids (see col. 7,
`
`lines
`
`40-49).
`
`Gentilucci et al. teach using N-methyl amino acids advantageously results in
`
`anabgues with improved pharmacological properties and stability (see §3.2.2. N-
`
`Alkylated Amino Acids; e.g., 5th paragraph). Gentilucci et al. further teach N-alkyl
`
`amino acids are commercially available (see §3.2.2. N-Alkylated Amino Acids; e.g., 2nd
`
`paragraph).
`
`Chatterjee et al. teach multiple methylation of peptides can improve the
`
`metabolic stability and intestinal permeability of peptides (see e.g., the abstract).
`
`The National Center for Biotechnology Information teaches that methylated Thr,
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`Lys and Val were known to the public as of the deposition date of 2007 (see PubChem
`
`CID: 14298176, 7010355 and 444080).
`
`At the time of the effective filing date, it would have been obvious to one of
`
`ordinary skill
`
`in the art to methylate the N-terminal Lys and/or the C-terminal Thr—OH,
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`Thr—NH2 and Val-OH of the tripeptides of Ferreira et al. and Brzoska et al. to arrive at
`
`the presently claimed invention. The artisan of ordinary skill would have been
`
`motivated to do so with a reasonable expectation of protecting the peptide from
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`protease degradation and thereby increasing the metabolic stability and intestinal
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`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 6
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`permeability of the peptide as taught by Zomaro, Gentilucci et al. and Chatterjee et al.
`
`Using the known technique of modifying the terminal ends of peptide with methylated
`
`amino acids for protection against degradation would have been obvious to one
`
`ordinary skill.
`
`Therefore, at the time of the effective filing date, the presently claimed invention
`
`was pr/ma fact-3 obvious to one of ordinary skill
`
`in the art.
`
`Response to Arguments
`
`In the remarks filed December 19, 2019, Applicants assert that the claimed
`
`invention is patentable over the cited references because there is no expectation based
`
`on the cited prior art, abne or in combination,
`
`that methylation results in improved
`
`chemical stability. See the remarks, pages 5-7.
`
`In particular, Applicants assert that the
`
`presently claimed compounds are characterized by increased chemical stability and
`
`improved bioavailability which were both unexpected and surprising in view of the cited
`
`prior art. Applicants argue that the stability properties mentioned in the cited
`
`references is with regard to stability against enzymatic degradation and stability against
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`enzymatic degradation is not predictive of stability of against chemical (non-enzymatic)
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`degradation.
`
`Applicants’ arguments have been fully considered but are not found persuasive.
`
`First, although the advantage of chemical stability imparted by methylation of amino
`
`acid residues in peptides was not recognized by the authors in the cited references, it
`
`was known in the prior art that the methylated form of an amino acid is chemically
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 7
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`stable (see Urnov 1; e.g., the abstract). Therein, in response to applicants' argument
`
`that methylation improved chemical stability to the claimed tripeptides,
`
`the fact that
`
`applicant has recognized another advantage which would flow naturally from following
`
`the suggestion of the prior art cannot be the basis for patentability when the
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`differences would othenNise be obvious. See EX part6 Oblaya, 227 USPQ 58, 60 (Bd.
`
`Pat. App. & Inter. 1985). The discovery of a previously unappreciated propelty of a
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`prior art composition, or of a scientific explanation for the prior art’s functioning, does
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`not render the old com position patentably new to the discoverer.
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`Secondly, with regard to improved bioavailability,
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`the artisan of ordinary skill
`
`would reasonably expect that methylation would increase the bioavailability of the
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`tripeptides of Ferreira et al. with modified with methylated amino acids based on the
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`teachings of Zomaro, Gentilucci et al. and Chatterjee et al. and the general knowledge
`
`in the art such as Urnov. There would have been a reasonable expectation because
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`methylation of amino acids improves stability, both chemically and enzymatically, as
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`evidenced by Zomaro, Gentilucci et al., Chatterjee et al. and Urnov. Because
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`methylation improves stability of the peptide, one of ordinary skill
`
`in the art would
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`reasonably expect a decrease in degradation, chemical and/or enzymatically, would
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`enhance the bioavailability of the tripeptides of Ferreira et al., thus, the increased
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`bioavailability Applicants assert was unexpected and surprising would not be considered
`
`unexpected and surprising given the knowledge in the prior art.
`
`the Power of a Small Amendment", The Journal ofA/umzwn, Volume 132,
`1 Urnov, “Methylation and the Genome:
`Issue 8, August 2002, Pages 24508‘24568
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`The rejection basis is maintained.
`
`Page 8
`
`Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over
`
`Ferreira et al. (US 5,389,615; 1995) and Brzoska et al. C‘oc-Melanocyte-Stimulating
`
`Hormone and Related Tripeptides: Biochemistry, Antiinflammatory and Protective
`
`Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune-
`
`Mediated Inflammatory Diseases", Endocrine Reviews, 2007; pp. 581-602) in view of
`
`Zomaro (US 5,718,882; 1998), Gentilucci et al. (“Chemical Modifications Designed to
`
`Improve Peptide Stability:
`
`Incorporation of Non-Natural Amino Acids, Pseudo-Peptide
`
`Bonds, and Cyclization", Current Pharmaceutical Design, 2010, pp. 3185-3203; cited in
`
`the IDS), Chatterjee et al. (“N-Methylation of Peptides: A New Perspective in Medicinal
`
`Chemistry”, Accounts of Chemical Research, 2008, pp. 1331-1342), and The National
`
`Center for Biotechnology Information (“6-Amino-2—(dimethylamino)hexanoic acid”
`
`(2007); “N-Methyl—L—valine" (2005) and “N-Methyl—L—threonine" (2006)) as applied to
`
`claims 1 and 10 above, and further in view of Grip et al. (“Use of atorvastatin as an
`
`anti-inflammatory treatment in Chron’s Disease", British Journal of Pharmacology, 2008,
`
`pp. 1085-1092).
`
`The teachings of Ferreira et al. Brzoska et al. Zomaro, Gentilucci et al.,
`
`Chatterjee et al. and The National Center for Biotechnobgy Information are discussed
`
`above. Ferreira et al. Brzoska et al. Zomaro, Gentilucci et al., Chatterjee et al. and The
`
`National Center for Biotechnology Information do not teach Chron’s disease as claimed.
`
`Grip et al. teach administering the anti-inflammatory agent atorvastatin to treat
`
`Chron’s Disease (see e.g., the abstract).
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 9
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`It would have been obvious to one of ordinary skill
`
`in the art at the time of the
`
`effective filing date to substitute the tripeptides of Ferreira modified with an N-
`
`methylated amino acid at the N- and/or C-termini because the tripeptides are anti-
`
`inflammatory peptides as taught Brzoska et al. The substitution of known equivalents is
`
`pr/ma facie obvious to one ordinary skill
`
`in the art.
`
`Therefore, at the time of the effective filing date, the presently claimed invention
`
`was prima facie obvious to one of ordinary skill
`
`in the art.
`
`Response to Arguments
`
`In the remarks filed December 19, 2019, Applicants argue that dependent claim
`
`13 incorporates all the aspects of the independent claims by virtue of its dependency
`
`and thus, claim 13 is nonobvious and patentable. Applicants do not offer further
`
`arguments regarding the above obviousness rejections beyond what was set forth with
`
`regard to the 35 U.S.C. § 103 rejection, above. To the extent that Applicants are
`
`merely repeating their previous argument, the Examiner contends that those issues
`
`were adequately addressed in the above section, which are incorporated in their
`
`entireties herein by reference
`
`Conclusion
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`No claim is allowed. THIS ACTION IS MADE FINAL. Applicant
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`is reminded of
`
`the extension of time policy as set forth in 37 CFR 1.136(a).
`
`A shortened statutory period for reply to this final action is set to expire THREE
`
`MONTHS from the mailing date of this action.
`
`In the event a first reply is filed within
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`TWO MONTHS of the mailing date of this final action and the advisory action is not
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`

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`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 10
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`mailed until after the end of the THREE-MONTH shortened statutory period, then the
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`shortened statutory perbd will expire on the date the advisory action is mailed, and any
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`extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of
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`the advisory action.
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`In no event, however, will the statutory perbd for reply expire
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`later than SIX MONTHS from the mailing date of this final action.
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`Correspondence
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Lianko G Garyu whose telephone number is (571)270-
`
`7367. The examiner can normally be reached on Monday through Friday 8:30 AM -
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`5:30 PM.
`
`Examiner interviews are available via telephone,
`
`in-person, and video
`
`conferencing using a USPTO supplied web-based collaboration tool. To schedule an
`
`interview, applicant
`
`is encouraged to use the USPTO Automated Interview Request
`
`(AIR) at http://www.uspto.gov/interviewpractice.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, Karlheinz R Skowronek can be reached on 571-272-9047. The fax phone
`
`number for the organization where this application or proceeding is assigned is 571-
`
`273-8300.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information 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
`
`

`

`Application/Control Number: 16/249,275
`Art Unit: 1658
`
`Page 11
`
`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). If you would like assistance from a USPTO
`
`Customer Service Representative or access to the automated information system, call
`
`800-786-9199 (IN USA OR CANADA) or 571-272-1000.
`
`/I_IANKO G GARYU/
`Primary Examiner, Art Unit 1658
`
`Lianko G. Garyu, Ph.D.
`Primary Examiner
`Art Unit 1658
`
`