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
`
`15/023,165
`
`03/18/2016
`
`Alex Loukas
`
`47COOK-FP10202PA
`
`7025
`
`759°
`”006
`DINSMORE & SHOHL LLP
`
`09/03/2019
`
`900 Wilshire Drive
`Suite 300
`my 44444044
`
`MIKNIS' ZACHARY J
`
`1654
`
`W
`
`NOTIFICATION DATE
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`DELIVERY MODE
`
`09/03/2019
`
`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.
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`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
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`following e—mail address(es):
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`MiehiganPatTM@dinsmore.eom
`
`PTOL-90A (Rev. 04/07)
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`

`

`0/7709 A0170” Summary
`
`Application No.
`15/023,165
`Examiner
`ZACHARY J MIKNIS
`
`Applicant(s)
`Loukas et al.
`Art Unit
`1654
`
`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 23 May 2019.
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a)D This action is FINAL.
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`2b)
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`This action is non-final.
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`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.
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`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 Expat/7e Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`5)
`Claim(s)
`
`1—3,5,8—10,14—16,18—28,31—42,45—46 and 48—50 is/are pending in the application.
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`5a) Of the above claim(s) 1—3,5,14—16,18—28,31—33 and 41—42 is/are withdrawn from consideration.
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`E] Claim(s)
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`is/are allowed.
`
`Claim(s) 8—10,34—40,45 and 49—50 is/are rejected.
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`Claim(s) 46 and 48 is/are objected to.
`
`) ) ) )
`
`
`
`are subject to restriction and/or election requirement
`E] Claim(s)
`* If any claims have been determined aflowabie. 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
`
`httpfiwww.”smogovmatentszinit_events[pph[index.'sp or send an inquiry to PPeredhack@g§ptg.ggv.
`
`Application Papers
`
`10)D The specification is objected to by the Examiner.
`
`11). The drawing(s) filed on 18 March 2016 is/are: a). accepted or b)[j 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).
`
`Priority under 35 U.S.C. § 119
`12). Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
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`a). All
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`b)l:] Some**
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`c)l:I None of the:
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`1.8 Certified copies of the priority documents have been received.
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`2.8 Certified copies of the priority documents have been received in Application No.
`
`3.. 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)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mail Date_
`U.S. Patent and Trademark Office
`
`3) C] 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 20190827
`
`

`

`Application/Control Number: 15/023,165
`Art Unit: 1654
`
`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, filed on or after March 16, 2013, is being examined
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`under the first inventor to file provisions of the AIA.
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`Claim Status
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`Claims 4, 6, 7, 11-13, 17, 29, 30, 43, 44, and 47 have been canceled. Claims 1-
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`3, 5, 8-10, 14-16, 18-28, 31-42, 45, 46, and 48-50 are pending. Claims 1-3, 5, 14-16,
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`18-28, 31 -33, 41, and 42 are withdrawn with traverse. Claims 8-10, 34-40, 45, and 48-
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`50 are being examined on the merits.
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`Continued Examination Under 37 CFR 1. 1 14
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`A request for continued examination under 37 CFR 1.114, including the fee set
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`forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this
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`application is eligible for continued examination under 37 CFR 1.114, and the fee set
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`forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action
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`has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 23 May
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`2019 has been entered.
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`Election/Restrictions
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`Applicant's election with traverse of Group II (claims 8-10 and 34-40) in the reply
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`filed on 15 November 2016 is acknowledged. The traversal is on the ground(s) that the
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 3
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`‘822 application as cited to break unity of invention is commonly owned, and thus not
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`prior art. This is not found persuasive because even allowing for the ‘822 application to
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`be disqualified as prior art under 35 U.S.C. 102(b)(2) owing to the common ownership
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`statement as filed, the special technical feature (a modified Ac—TMP-2 protein) is still
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`known as found in the rejection presented below under 35 U.S.C. 103.
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`The requirement is still deemed proper and is therefore made FINAL.
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`Claims 1-3, 5, 14-16, 18-28, 31-33, 41, and 42 are withdrawn from further
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`consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention,
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`there being no allowable generic or linking claim. Applicant timely traversed the
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`restriction (election) requirement in the reply filed on 15 November 2016.
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`I. New Rejections:
`
`Claim Rejections - 35 USC § 1 12
`
`The following is a quotation of 35 U.S.C. 112(b):
`(b) CONCLUSION—The specification shall conclude with one or more claims particularly
`pointing out and distinctly claiming the subject matter which the inventor or a joint inventor
`regards as the invention.
`
`The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph:
`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.
`
`Claim 50 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second
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`paragraph, as being indefinite for failing to particularly point out and distinctly claim the
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`subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards
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`as the invention.
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`Claim 50 recites the limitation that “the plurality of acidic C-terminal amino acids
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`comprises amino acids 141 -228 of full length or wild type AC-TMP-2 protein”. This
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`language is indefinite because it does not correspond to a set position to determine
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 4
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`where the acidic C-terminal amino acids begin. As set forth in a previous rejection, the
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`art recognizes that full-length Ac-TMP-2 has a 16-amino acid long secretion signal. The
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`claim language refers to residues 141 -228 of full length or wild type Ac-TMP-2. It is not
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`clear whether residues 141-228 are numbered from the start of the full-length protein, or
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`whether the numbering is in reference to residues after removal of the secretion signal.
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`The metes and bounds of the claim are unclear.
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`Claim Rejections - 35 USC § 103
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`In the event the determination of the status of the application as subject to AIA 35
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`U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any
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`correction of the statutory basis for the rejection will not be considered a new ground of
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`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
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`the same under either status.
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`This application currently names joint inventors. In considering patentability of the
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`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 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.
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`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:
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 5
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`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, if the 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 by the manner in which the invention was made.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 US. 1, 148
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`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:
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`1. Determining the scope and contents of the prior art.
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`2. Ascertaining the differences between the prior art and the claims at issue.
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`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.
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`1. Claims 8, 49, and 50 are rejected under 35 U.S.C. 103 as being unpatentable
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`over Zhan et al. (Moi. & Biochem. Parasitology 162:142-148, published 2008, hereafter
`
`referred to as Zhan) and Loukas et al. (WO 2013/134822 A1, published 19 September
`
`2013, filed 13 March 2013, priority to 13 March 2012, hereafter referred to as ‘882).
`
`The Zhan art teaches the cloning of Ac—TMP-2 (see e.g. Abstract). Zhan teaches
`
`that the protein is 244 amino acids in length, and contains a N-terminal 16 amino acid-
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`long signal sequence that is cleaved between Ala16 and Ala17 of full-length Ac—TMP-2
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`(see e.g. Section 3.1, Figure 1). An N-linked glycosylation site is taught at position 64
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`(see e.g. Section 3.1 ). Zhan also teaches that the Ac-TMP-2 has a C-terminal multicopy
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`repeat of KTVEENDE that is similar to the 3’ repeats of ring-infected erythrocyte surface
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`antigen of P. falciparum (see e.g. Section 3.1), suggesting it is not a portion relevant to
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`the metalloproteinase activity. The recombinant Ac—TMP-2 peptide of Zhan is taught to
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`inhibit MMP-13, MMP-7, and MMP-2 strongly (see e.g. Figure 5 and Section 3.5). The
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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 6
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`Ac—TMP-2 peptide is taught to contain the canonical C-X-C sequence found in other
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`nematode TlMPs (see e.g. Section 4). In discussing the strong inhibition of MMP-2,
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`MMP-7, and MMP-13 by Ac—TMP-2, Zhan teaches that MMPs play roles in modulating
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`host inflammatory reactions (see e.g. p.147 Col.1 112). In particular, Zhan suggests that
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`hookworms secrete Ac—TMP-2 to inhibit proinflammatory MMPs to down-regulate host
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`immune responses (see e.g. p.147 Col.1 112).
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`The difference between Zhan and the claimed invention is that Zhan does not
`
`explicitly teach removal of the secretion signal, N-linked glycosylation site, or C-terminal
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`acidic amino acids, nor does Zhan explicitly teach that Ac—TMP-2 is capable of reducing
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`and/or alleviating inflammation upon administration to a subject in need thereof.
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`The ‘882 application teaches alleviation of inflammation by administering Ac-
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`TMP-2 or a biologically active fragment thereof (see e.g. claim 1). The ‘882 application
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`defines a biologically active fragment as being a portion that has no less than 10-95% of
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`the activity of the wild-type Ac-TMP-2 (see e.g. p.16 lines 15-19) and can constitute
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`anywhere from 220-50 contiguous amino acids of mature Ac-TMP-2 (see e.g. p.16 lines
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`22-26
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`It would be obvious to one of ordinary skill in the art before the effective filing
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`date of the claimed invention from the teachings of Zhan regarding the signal sequence
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`that a recombinant protein should be prepared by removing said signal sequence amino
`
`acids from the N-terminus. It would also be obvious to remove the N-linked
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`glycosylation site to reduce heterogeneity in expressed protein by mutating the Asn to a
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`Gin that cannot be glycosylated and is structurally similar to Asn (as is known for other
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`tissue inhibitors of metalloproteinases, see e.g. Caterina et al. Biochim. Biophys. Acta
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 7
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`14:21 -34, published 14 October 1998). The resulting peptide at a minimum comprises
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`SEQ ID NO:4 as it lacks the N-terminal secretion signal and has a removal of the N-
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`linked glycosylation site by an N640 mutation. The Zhan peptide is then obvious to
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`modify with the deletions as claimed as part of the ‘882 peptide encompassing Ac-TMP-
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`2 fragments and their use to treat inflammation. Since ‘882 specifically claims the
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`fragments in an anti-inflammatory manner it would be obvious to use it in the same way
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`as in Zhan. The specific instructions to delete residues in Ac-TMP-2 down to 50
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`residues total length would lead in a stepwise fashion to removal of C-terminal residues
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`including acidic segments. Furthermore, given the teachings that Ac—TMP-2 inhibits
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`MMP-2, MMP-7, and MMP-13 and the knowledge in the art that each are involved in
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`pro-inflammatory responses, one of ordinary skill would find it obvious to apply Ac—TMP-
`
`2 to reduce inflammation in a subject in need thereof. This is especially true given that
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`Zhan explicitly suggests that hookworms utilize Ac—TMP-2 for this exact purpose in
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`order to evade immune system detection and ‘882 claims treatment of inflammation with
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`Ac-TMP-2 fragments. The Zhan art provides specific motivation to remove the signal
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`sequence since it is not a functional part of the peptide, and provides a strong
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`suggestion that Ac—TMP-2 can be utilized as an anti-inflammatory modulator. The
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`teachings of the peptide and usefulness in Zhan provide a reasonable expectation that
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`application to a patient suffering from inflammation would be successful in reducing
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`inflammation, especially given the inhibition of the various MMP functions by Ac—TMP-2.
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`Again, as with Zhan there would be a reasonable expectation of success because the
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`peptide was known for anti-inflammatory use and ‘882 provides a direct teaching as to
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 8
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`removal of residues in the mature protein. The invention would be prima facie obvious
`
`to one of ordinary skill in the art before the effective filing date of the claimed invention.
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`With respect to claim 49, the removal of C-terminal residues based on ‘882
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`removes at least one EEN sequence.
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`With respect to claim 50, the removal of C-terminal residues to leave a 50-
`
`residue fragment as in ‘882 would remove residues 141 -228.
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`2. Claims 9, 10, 34-37, 40, and 45 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Zhan et al. (Moi. & Biochem. Parasitology 162:142-148, published
`
`2008) and Loukas et al. (WO 2013/134822 A1, published 19 September 2013, filed 13
`
`March 2013, priority to 13 March 2012) as applied to claim 8 above, and further in view
`
`of Tremain WJ (Neth. J. Med. 50:812-4, published 1997, hereafter referred to as
`
`Tremain).
`
`The relevance of Zhan and ‘882 is set forth above. The difference between the
`
`prior art and the claimed invention is that neither reference teaches that the
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`inflammation is associated with any sort of disease or disorder, nor that the disease or
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`disorder is refractory to baseline treatment. Additionally, neither reference teaches the
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`diseases in claims 34-37 or additional treatment in claim 40.
`
`Tremaine teaches that refractory IBS is a persistent acute disease despite anti-
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`inflammatory interventions (see e.g. Abstract). Tremaine teaches that azathiprine, 6-
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`mercaptopurine, methotrexate, cyclosporine, and experimental strategies are treatment
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`options, and that 6-mercaptopurine is effective in ~75% of Crohn's disease patients (see
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 9
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`e.g. Abstract). Tremaine also teaches cyclosporine may be useful for severe ulcerative
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`colitis (see e.g. Abstract).
`
`It would be obvious to one of ordinary skill in the art before the effective filing
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`date of the claimed invention that in the case of refractory IBS, including Crohn's
`
`disease and severe ulcerative colitis, that the anti-inflammatory Ac—TMP-2 of Zhan and
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`‘882 could serve as a potential anti-inflammatory modulator as compared to the
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`baseline treatments that prove to be ineffective. The motivation to seek other anti-
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`inflammatory compounds comes from the teachings in Tremaine that current anti-
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`inflammatory treatments can prove ineffective, motivating one of ordinary skill to seek
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`other anti-inflammatory modulators for use in treatment. Since Zhan and ’882 establish
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`that anti-inflammatory activity is found in Ac—TMP-2, one of ordinary skill would
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`reasonably seek to utilize it in treatment of refractory IBS. As Ac—TMP-2 possesses anti-
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`inflammatory activity and is not a baseline therapy already utilized for treatment of IBS,
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`one of ordinary skill would expect it to provide a measure of inflammatory relief in IBS
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`patients. The invention would be prima facie obvious to one of ordinary skill in the art
`
`before the effective filing date of the claimed invention.
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`With respect to claim 9, the administration of Ac—TMP-2 to generally treat
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`inflammation by inhibiting MMP pathways would result in treatment of the inflammation,
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`regardless of how the inflammation arises. In this case, the inflammation would be
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`associated with IBS (a known feature of IBS), and one of ordinary skill would expect the
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`inflammation to be treated via inhibition of the MMP pathways by Ac—TMP-2.
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`With respect to claim 10, Tremaine sets forth already that the IBS is refractory to
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`baseline treatment with known anti-inflammatory compounds.
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
`
`Page 10
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`With respect to claims 34-37, the refractory IBS, Crohn’s disease, and ulcerative
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`colitis of Tremaine read upon the genera and species as claimed.
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`With respect to claims 40 and 45, the Tremaine art sets forth several other
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`therapies that are useful for Crohn’s and ulcerative colitis patients in at least certain
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`situations, including cyclosporine (an immunosuppressant). It would be obvious that
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`said treatments should be combined with the anti-inflammatory treatment of Zhan in
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`order to treat the Crohn's/UC on multiple levels, especially with the expectation that
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`additive treatment would be more effective than treatment with a single compound.
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`3. Claims 9, 38, and 39 are rejected under 35 U.S.C. 103 as being unpatentable
`
`over Zhan et al. (Moi. & Biochem. Parasitology 162:142-148, published 2008) and
`
`Loukas et al. (WO 2013/134822 A1, published 19 September 2013, filed 13 March
`
`2013, priority to 13 March 2012) as applied to claim 8 above, and further in view of
`
`Cazzola et al. (Eur. Resp. J. 40:724-741, published 10 April 2012, hereafter referred to
`
`as Cazzola)
`
`The relevance of Zhan and ‘882 is set forth above. The difference between the
`
`prior art and the claimed invention is that neither reference teaches that the disease
`
`associated with inflammation is a respiratory disease, including asthma, emphysema,
`
`chronic bronchitis, or COPD.
`
`Cazzola teaches that a hallmark of COPD is inflammation in the lungs (see e.g.
`
`p.724 Col.1 111). Cazzola teaches that anti-inflammatory needs of COPD patients are
`
`not met (see e.g. p.724 Col.1 112 to C012 11). Statins are discussed as an anti-
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 11
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`inflammatory agent of interest, and it is noted that they reduce production of MMPs, in
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`particular MMP-1, MMP-2, and MMP-9 (see e.g. p.734 Col.2 114).
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`It would be obvious to one of ordinary skill in the art before the effective filing
`
`date of the claimed invention to utilize the anti-inflammatory Ac—TMP-2 as taught in
`
`Zhan and ‘882 for treatment of COPD as taught in Cazzola by focusing on inflammation
`
`present in COPD patients. The motivation to utilize Ac—TMP-2 comes from the Cazzola
`
`art, which teaches the concept of utilizing a wide variety of anti-inflammatory modulators
`
`as well as focusing on those that modulate MMP production. There would be a
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`reasonable expectation of success because Ac—TMP-2 acts on MMPs, leading to
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`reasonable use for treatment of COPD that is largely an inflammatory disease. Since
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`Ac—TMP-2 was known to be anti-inflammatory, one of ordinary skill in the art would also
`
`expect it to influence inflammation in COPD by acting on MMP pathways. The invention
`
`would be prima facie obvious to one of ordinary skill in the art before the effective filing
`
`date of the claimed invention.
`
`With respect to claim 9, Cazzola as set forth above establishes that inflammation
`
`is associated with COPD.
`
`With respect to claims 38 and 39, COPD as taught in Cazzola is a species as
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`recited from the genus of respiratory system diseases.
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`Double Parenting
`
`The nonstatutory double patenting rejection is based on a judicially created
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`doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the
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`unjustified or improper timewise extension of the “right to exclude” granted by a patent
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 12
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`and to prevent possible harassment by multiple assignees. A nonstatutory double
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`patenting rejection is appropriate where the conflicting claims are not identical, but at
`
`least one examined application claim is not patentably distinct from the reference
`
`claim(s) because the examined application claim is either anticipated by, or would have
`
`been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46
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`USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed.
`
`Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum,
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`686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619
`
`(CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
`
`A timely filed terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321 (d)
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`may be used to overcome an actual or provisional rejection based on nonstatutory
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`double patenting provided the reference application or patent either is shown to be
`
`commonly owned with the examined application, or claims an invention made as a
`
`result of activities undertaken within the scope of a joint research agreement. See
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`MPEP § 717.02 for applications subject to examination under the first inventor to file
`
`provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) -
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`706.02(l)(3) for applications not subject to examination under the first inventor to file
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`provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR
`
`1.321 (b).
`
`The USPTO Internet website contains terminal disclaimer forms which may be
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`used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application
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`in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26,
`
`PTO/AlA/25, or PTO/AlA/26) should be used. A web-based eTerminal Disclaimer may
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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`Page 13
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`be filled out completely online using web-screens. An eTerminal Disclaimer that meets
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`all requirements is auto-processed and approved immediately upon submission. For
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`more information about eTerminal Disclaimers, refer to
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`www.uspto.gov/patents/process/file/efs/guidance/eTD-info-l.jsp.
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`Claims 8-10, 34-40, 45, and 47 are rejected on the ground of nonstatutory
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`double patenting as being unpatentable over claims 1-3, 11-15, and 19 of U.S. Patent
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`No. 9,637,527 in view of Zhan et al. (Moi. & Biochem. Parasitology 162:142-148,
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`published 2008) and Loukas et al. (WO 2013/134822 A1, published 19 September
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`2013, filed 13 March 2013, priority to 13 March 2012). Although the claims at issue are
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`not identical, they are not patentably distinct from each other because the ‘527 patent
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`claims methods of treatment using full-length Ac—TMP-2, which can reasonably be
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`substituted by the mature peptide of Zhan and read upon the instant claims.
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`The ‘527 patent claims a method of treating inflammation using a peptide of SEQ
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`ID NO:2 (see e.g. claim 1), which is full-length Ac—TMP-2 containing a secretion signal.
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`The difference between '527 and the claimed invention is that '527 does not claim use
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`of a modified Ac—TMP-2 protein comprising SEQ ID NO:4.
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`The relevance of Zhan and ‘882 has been set forth above. As argued, the Zhan
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`and ‘882 art reasonably makes obvious production of mature Ac—TMP-2 lacking the N-
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`terminal signal sequence, removal of the N-linked glycosylation site (a N640 mutation),
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`and C-terminal deletions.
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`It would be obvious to one of ordinary skill in the art before the effective filing
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`date of the claimed invention to substitute the truncated Ac—TMP-2 of Zhan and ‘882 for
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`the wild-type full-length protein as claimed in '527. The motivation to substitute comes
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`from the fact that both proteins are relatives to one another. Since highly similar
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`compounds are being utilized, one of ordinary skill would expect the same anti-
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`inflammatory properties to be maintained, especially given that Zhan teaches similar
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`effects. The invention would be prima facie obvious to one of ordinary skill in the art
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`before the effective filing date of the claimed invention.
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`With respect to claims 9 and 10, the ‘527 patent claims the same source of
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`inflammation and refractory response to baseline therapies (see e.g. claims 2 and 3).
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`With respect to claims 34-37, the ‘527 patent claims the same diseases of the
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`digestive tract, including Crohn’s and ulcerative colitis (see e.g. claims 11-13).
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`With respect to claims 38 and 39, the ‘527 patent claims the same respiratory
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`diseases, including asthma, emphysema, chronic bronchitis, and COPD (see e.g.
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`claims 14 and 15).
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`With respect to claim 40, the ‘527 patent claims further administration of an
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`additional agent, including the same genera as instantly claimed (see e.g. claim 19).
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`With respect to claim 43, the ‘527 patent in light of Zhan results in a peptide with
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`at least 95% identity to SEQ ID NO:1 or SEQ ID NO:4.
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`With respect to claim 44, the ‘527 patent in light of Zhan provides a N-terminal C-
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`X-C motif.
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`With respect to claim 45, the ‘527 patent claims further administration of an
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`additional agent, including the same genera as instantly claimed (see e.g. claim 19).
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`II. Withdrawn Relections:
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`Application/Control Number: 15/023,165
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`The rejection of claims 8-10, 34-40, 43, and 44 under 35 U.S.C. 112(a) for written
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`description is withdrawn in light of the amendment filed 12 October 2018.
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`The rejection of claims 8-10, 34-40, 43, and 44 under 35 U.S.C. 112(b) is
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`withdrawn in light of the amendment filed 12 October 2018.
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`The rejection of claims 8 and 47 under 35 U.S.C. 103 as being unpatentable over
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`Zhan is withdrawn in light of the amendment filed 23 May 2019.
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`The rejection of claims 9, 10, 34-37, 40, and 45 under 35 U.S.C. 103 as being
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`unpatentable over Zhan in view of Tremain is withdrawn in light of the amendment filed
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`23 May 2019.
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`The rejection of claims 9, 38, and 39 under 35 U.S.C. 103 as being unpatentable
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`over Zhan in view of Cazzola is withdrawn in light of the amendment filed 23 May 2019.
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`The rejection of claims 8-10, 34-40, 45, and 47 for nonstatutory double patenting
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`as being unpatentable over USP 9,637,527 in view of Zhan is withdrawn in light of the
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`amendment filed 23 May 2019.
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`Allowable Subject Matter
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`Claims 46 and 48 are objected to as being dependent upon a rejected base
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`claim, but would be allowable if rewritten in independent form including all of the
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`limitations of the base claim and any intervening claims.
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`The following is a statement of reasons for the indication of allowable subject
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`matter: The claims are drawn to the method of claim 8 for reducing or alleviating
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`inflammation in a subject, where the subject is administered a modified Ac-TMP-2
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`protein. The instant claims recite that the protein consists of SEQ ID NOs:1 or 5, which
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`are determined to be free of the art. The closest art (the previously cited Zhan art)
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`teaches the full-length Ac-TMP-2 protein and reasonably leads to removal of the N-
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`terminal signal sequence. However, nothing in Zhan or any other prior art suggest
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`removal of C-terminal repeats as found in Ac-TMP-2 to arrive at SEQ ID NOs:1 or 5,
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`both of which demonstrate removal of multiple repeat sequences from the C-terminus of
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`wild-type Ac-TMP-2. The claimed method of using these novel and unobvious Ac-TMP-
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`2 proteins is determined itself to be novel and unobvious, and otherwise finding support
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`in the specification to satisfy 35 U.S.C. 101 and 112.
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`No claims are allowed.
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`Conclusion
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`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to ZACHARY J MIKNIS whose telephone number is
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`(571)272-7008. The examiner can normally be reached on M-F 8AM-5PM.
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`Examiner interviews are available via telephone, in-person, and video
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`conferencing using a USPTO supplied web-based collaboration tool. To schedule an
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`interview, applicant is encouraged to use the USPTO Automated Interview Request
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`(AIR) at http://www.uspto.gov/interviewpractice.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, James Alstrum-Acevedo can be reached on (571) 272-5548. The fax phone
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`number for the organization where this application or proceeding is assigned is 571 -
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`273-8300.
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`

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`Application/Control Number: 15/023,165
`Art Unit: 1654
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`/ZACHARY J MIKNIS/
`
`Examiner, Art Unit 1654
`
`