UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria, Virginia 2231371450
`www.uspto.gov
`
`15/999,517
`
`08/20/2018
`
`Lance L. Gooberman
`
`CU-73640 JPL
`
`4474
`
`LADAS & PARRY LLP
`
`224 SOUTH MICHIGAN AVENUE
`SUITE 1600
`
`CHICAGo, IL 60604
`
`ZHANG YANZHI
`
`1617
`
`PAPER NUMBER
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`NOTIFICATION DATE
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`DELIVERY MODE
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`06/17/2019
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`ELECTRONIC
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`Please find below and/or attached an Office communication concerning this application or proceeding.
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`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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`ChicagoUSPTO @ ladas.net
`
`PTOL-90A (Rev. 04/07)
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`

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`0,7709 A0170” Summary
`
`Application No.
`15/999,517
`Examiner
`YANZHI ZHANG
`
`Applicant(s)
`Gooberman, Lance L.
`Art Unit
`AIA (FITF) Status
`1617
`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).
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`Status
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`1). Responsive to communication(s) filed on 05/29/19.
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a). This action is FINAL.
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`2b) C] 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.
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`Disposition of Claims*
`5)
`Claim(s)
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`1—20 is/are pending in the application.
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`5a) Of the above claim(s) 17—20 is/are withdrawn from consideration.
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`E] Claim(s)
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`is/are allowed.
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`Claim(s) fl is/are rejected.
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`Claim(s) fl is/are objected to.
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`) ) ) )
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`6 7
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`8
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`
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`are subject to restriction and/or election requirement
`E] Claim(s)
`9
`* If any claims have been determined aflowabie. you may be eligible to benefit from the Patent Prosecution Highway program at a
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`participating intellectual property office for the corresponding application. For more information, please see
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`http://www.jjgptggQV/patents/init_event§/pph/index.'sp or send an inquiry to PPeredhack@g§ptg.ggv.
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`Application Papers
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`10)D The specification is objected to by the Examiner.
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`is/are: a)C] 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)[:] 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)D All
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`b)U Some**
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`C)U None of the:
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`1C] Certified copies of the priority documents have been received.
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`21:] Certified copies of the priority documents have been received in Application No.
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`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)).
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`** See the attached detailed Office action for a list of the certified copies not received.
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`Attachment(s)
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`1)
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`Notice of References Cited (PTO-892)
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`2) D Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`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)
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`Office Action Summary
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`Part of Paper No./Mai| Date 20190611
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 2
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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 under the
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`first inventor to file provisions of the AIA.
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`Claim Status
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`This is in response to papers file on May 29, 2019. Claims 1, 4, 11, and 14.have been
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`amended. No claim has been newly added or cancelled. Claims 17—20 have been withdrawn for
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`the reason of record. Accordingly, claims 1—16 are under consideration on the merit.
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`Previous Rejections
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`Rejections and objections not reiterated from previous office actions are hereby withdrawn
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`in view of amendments dated 05/29/19. The following rejections and/or objections are either
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`reiterated or newly applied necessitated by amendments dated 05/29/19. They constitute the
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`complete set presently being applied to the instant application.
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`Claim Objections
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`Claims 17—20 are objected to because of the following informalities:
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`The status of claims 17—20 should be “Withdrawn”, not “previous presented”. As
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`applicant confirmed (page 1 of remarks), claims 17—20 have been Withdrawn from further
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`consideration as a result of restriction.
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`Appropriate correction is required.
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`Claim Rejections - 35 USC § 112(1)) (new)
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 3
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`The text of those sections of Title 35 of the US. Code not included in this action can be
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`found in a prior Office action.
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`Claims 1—16 are 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 subject
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`matter which the inventor or a joint inventor, or for pre—AIA the applicant regards as the
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`invention.
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`A broad range or limitation together with a narrow range or limitation that falls within the
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`broad range or limitation (in the same claim) is considered indefinite, since the resulting claim
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`does not clearly set forth the metes and bounds of the patent protection desired. See MPEP §
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`2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex
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`parte Wu, 10 USPQ2d 2031, 2033 (Ed. Pat. App. & Inter. 1989), as to where broad language is
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`followed by "such as" and then narrow language. The Board stated that this can render a claim
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`indefinite by raising a question or doubt as to whether the feature introduced by such language is
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`(a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required
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`feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131
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`USPQ 74 (Bd. App. 1961); Exparte Hall, 83 USPQ 38 (Bd. App. 1948); and Exparte Hasche,
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`86 USPQ 481 (Ed. App. 1949). In the present instance, claim 1 recites a broad limitation by
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`using the transitional phrase “comprising”, and the claim also recites a narrow limitation by
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`using the transitional phrase “consisting of”. Therefore, claim is considered indefinite.
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`Appropriate action is required.
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`Claims 2—16 ultimately depend on the base claim, thus are included in the rejection.
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`In the interest of compact prosecution, claim 1 is search and examined as a composition
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`for injection consisting of an opioid antagonist, a steroidal anti—inflammatory agent, and an
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 4
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`injection vehicle because the narrow transitional phrase controls the scope. The opioid
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`antagonist and a polymeric binder are in the form of microparticles, while the steroid is either
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`mixed with the vehicle (in the form of a solution) or encapsulated in the microparticles together
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`with the opioid antagonist based on claim 3 and specification (e.g. [0018] and [0047]).
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`It is suggested that claim 1 is amended by adding “wherein the (or said) steroidal anti—
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`inflammatory agent is either mixed with the vehicle (in the form of a solution) or encapsulated in
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`the microparticles.” at the end of claim 1.
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`Response to arguments
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`Applicant's arguments filed 05/29/2019 have been fully considered towards the previous
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`112(b) rejection, they are persuasive. Thus, the rejection has been withdrawn in view of
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`amendments and arguments dated 05/29/ 19.
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`The above 112(b) rejection is newly applied due to amendments dated 05/29/19. The
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`amendments and arguments dated 05/29/ 19 do not applied to the new rejection.
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`Claim Rejections - 35 US C § 112(d) (maintained)
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`The text of those sections of Title 35 of the US. Code not included in this action can be
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`found in a prior Office action.
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`Claim 3 is rejected under 35 USC. 112(d) or pre—AIA 35 USC. 112, 4th paragraph, as
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`being of improper dependent form for failing to further limit the subject matter of the claim upon
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`which it depends, or for failing to include all the limitations of the claim upon which it depends.
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`Claim 3 recites the limitation of “wherein steroidal anti—inflammatory agent is encapsulated in
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`the microparticles”. However, claim 1 uses the closed transitional phrase “consisting of", which
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 5
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`do not allow for the presence of additional unrecited components. As written, a steroidal anti—
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`inflammatory agent is a separate component from the microparticles. Thus, claim 3 is broader
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`than claim 1 (the independent claim).
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`Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper
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`dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that
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`the dependent claim(s) complies with the statutory requirements.
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`Claim 3 is not addressed in the art rejection because a prior art meet the limitations of
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`claim 1 reads on claim 3.
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`Response to arguments
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`Applicant's arguments filed 05/29/2019 have been fully considered, they are not
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`persuasive.
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`Applicant argues that claim 1 has been amended to recite “microparticles comprising...”
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`and using “consisting” is merely a typo.
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`This argument is not persuasive because of the following reasons:
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`1). the amendment of changing transitional phrase from “microparticles consisting” to
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`“microparticles comprising...” is NOT merely a typo. This amendment changes the scope of
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`claim 1 from narrow to broad.
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`2). the amendment of microparticle would not allow the applicant broadening the scope
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`of claim 1 because “consisting of” in line 1 of claim 1 has higher ranking in the hierarchies of
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`limitations in claim 1.
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`It is suggested that claim 1 is amended by adding “wherein the (or said) steroidal anti—
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`inflammatory agent is either mixed with the carrier vehicle (i.e. in the form of a solution) or
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 6
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`encapsulated in the microparticles.” at the end of claim 1. It is believed that the suggested
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`amendment would allow claim 3 as a proper dependent claim.
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`Claim Rejections - 35 US C § 103
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`The text of those sections of Title 35 of the US. Code not included in this action can be
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`found in a prior Office action.
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`Claims 1-2, 4, and 6-16 are rejected under 35 U.S.C. 103 as obvious over Ramstack
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`et al (“Ramstack”, US 20030113380 A1, published June 19, 2003) and Aldemir et al
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`(“Aldemir”, non-patent literature, Transplantation Proceedings, vol. 48, pp. 2769-2772,
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`2016).
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`Claims 1—2, 4, and 6—16 embrace a composition for injection into a host, consisting of:
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`1). microparticles consisting essentially of an opioid antagonist and a polymeric binder
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`selected from the group consisting of poly(glycolic acid), poly—d,l—lactic acid, poly—l—lactic acid,
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`copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone,
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`polydioxanone, poly(ortho carbonates), poly(acetals), poly(lactic acid—caprolactone),
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`polyorthoesters, poly(glycolic acid—caprolactone), polyanhydrides, and polyphosphazines;
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`2). an injection vehicle, wherein said injection vehicle consists of water, a viscosity
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`enhancing agent, a wetting agent, and a tonicity adjusting agent; and
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`3). a steroidal anti—inflammatory agent.
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`Ramstack is directed to an injectable compositions include microparticles suspended in an
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`aqueous injection vehicle having a viscosity of at least 20 cp at 20°C (abstract, readable on the
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`limitations of 2) in the instant claim 1). Ramstack discloses that the composition comprises
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`microparticles having a polymeric binder, with a mass median diameter of at least about 10
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 7
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`um and the composition also includes an injection vehicle that consists of 3% by volume sodium
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`carboxymethyl cellulose, 1% by volume polysorbate 20, 0.9% by volume sodium chloride, and
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`a remaining percentage by volume of water. The microparticles are suspended in the injection
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`vehicle at a concentration of greater than about 30 mg/ml to form a suspension, the fluid phase
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`of the suspension has a viscosity at 20.degree. C. of at least about 30 cp, 40 cp, 50 cp, and 60 cp.
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`The composition may also comprise a viscosity enhancing agent, a density enhancing agent, a
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`tonicity enhancing agent, and/or a wetting agent. The composition can be administered to a host
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`by injection ([0015], readable on the limitations of components 1) and 2) in the instant claim 1,
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`the limitations of the instant claims 4, 7—12, and 14—15). Ramstack also discloses that biologically
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`active agents include non—steroidal antifertility agents; opioid receptor antagonists, such as
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`naltrexone and naloxone; anti—inflammatory agents such as, hydrocortisone, prednisolone
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`([0091], readable on the ingredient 3) in the instant claim 1 and the limitation of the instant claim
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`2). Ramstack further discloses that polymeric binder is selected from the group consisting of
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`poly(glycolic acid), poly—d,l—lactic acid, poly—l—lactic acid, copolymers of the foregoing,
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`poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxanone, poly(ortho
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`carbonates), poly(acetals), poly(lactic acid—caprolactone), polyorthoesters, poly(glycolic acid—
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`caprolactone), polyanhydrides, polyphosphazines, etc.; the preferred polymeric binder is poly(d,l—
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`lactide—co—glycolide) having a molar ratio of lactide to glycolide in the range of from about 85:15
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`to about 50:50 (claims 18—19 of Ramstack, readable on the limitation of the polymeric binder in
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`the instant claims 1, 6, and 16).
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`While teaching microparticles suitable for various therapeutic agents including naloxone;
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`and hydrocortisone, Ramstack does not expressly teach combination therapy of using an opioid
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`antagonist and steroid. This deficiency is cured by Aldemir.
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 8
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`Aldemir is directed to treatment of Opioid dependence with buprenorphine/Naloxone
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`after liver transplantation (title, combo therapy of a narcotic and an opioid antagonist).
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`Aldemir recognizes that opioid dependence is an increasing public health problem
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`(abstract). Aldemir teaches that liver transplantation patients are treated with
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`buprenorphine/Naloxone for Opioid dependence with immunosuppressive, steroid, antiviral
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`among other drugs.
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`It would have been obvious for one of ordinary skill in the art, as of the effective filing
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`date of the claimed invention, to choose adding steroid taught by Aldemir as the particular drug
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`to be incorporated into the pharmaceutical composition of Ramstack. A person of ordinary skill
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`would have been motived to do so because Aldemir has taught the need of using combination
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`therapy depending on the patient’s medical condition. Thus, in view of the teachings Ramstack
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`Aldemir, there would have been a reasonable expectation that a composition comprising an
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`opioid antagonist and a steroidal anti—inflammatory agent could be successfully prepared and
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`used in a method for treating a complicated medical conditions.
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`Regarding the concentrations of the ingredients, viscosity, and particle diameter, these are
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`considered result—effective variables. Principles of Law are“[Where the general conditions of a
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`claim are disclosed in the prior art, it is not inventive to discover the optimum or workable
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`ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955). This rule is
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`limited to cases in which the optimized variable is a “result—effective variable.” In re Antonie,
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`559 F.2d 618, 620 (CCPA 1977). In this case, Ramstack discloses concentration and viscosity
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`fall within the claimed ranges (see rejection set forth above). Additionally, Ramstack indicates
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`that adjusting viscosity according to the particle size is known ([0012]).
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 9
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`Claim 5 is rejected under 35 U.S.C. 103(a) as being unpatentable over Ramstack et
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`al (US 20030113380 A1, published June 19, 2003) and Aldemir et al (“Aldemir”, non-patent
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`literature, Transplantation Proceedings, vol. 48, pp. 2769-2772, 2016) as applied to claims
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`1-2, 4, and 6-16 in View of Aventis (non-patent literature, Food and Drug Administration
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`medicine information, published online March, 2004).
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`It should be noted that only pertinent portion of Aventis document is cited (downloaded
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`from https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=1787).
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`The teachings of Ramstack and Aldemir have been discussed as applied to claims 1—2, 4,
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`6—16. While teaching combo—therapy with an opioid antagonist and a steroidal anti—inflammatory
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`agent, Ramstack and Aldemir do not expressly teach the steroidal anti—inflammatory agent is
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`triamcinolone acetonide as claimed. However, the deficiency is cured by Aventis.
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`Aventis is directed to Nasacort aq. (triamcinolone acetonide) spray, metered (title).
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`Aventis teaches that triamcinolone acetonide is approximately 8 times more potent than prednisone
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`(see 1St paragraph under the heading clinical pharmacology of page 1 of 8, readable on the
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`limitation of the instant claim 5).
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`It would have been obvious for one of ordinary skill in the art, as of the effective filing
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`date of the claimed invention, to choose triamcinolone acetonide taught by Aventis as the
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`particular steroidal anti—inflammatory agent to be incorporated into composition of Ramstack. A
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`person of ordinary skill would have been motived to do so because Aventis has taught that
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`triamcinolone acetonide is approximately 8 times more potent than prednisone. Thus, in view of
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`the teachings Ramstack and Aventis, there would have been a reasonable expectation that a
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`composition comprising opioid antagonist and triamcinolone acetonide could be successfully
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`prepared and used in a medicament.
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
`
`Response to arguments
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`Page 10
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`Applicant's arguments filed 05/29/2019 have been fully considered, they are not
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`persuasive for the following reasons.
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`Applicant argues that Aldemir does not disclose a steroid is applied simultaneously with
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`an opioid antagonist. Applicant also argues that Aldemir reveals (page 2769) that hepatitis C
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`virus (HCV) infection is one of the most important medical problems raised from intravenous
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`use of opioids and the purpose of steroid application in Aldemir is absolutely different from the
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`purpose of using steroid in admixture of opioid antagonist as disclosed in the present application.
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`In response to applicant's above arguments, the fact that applicant has recognized another
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`advantage which would flow naturally from following the suggestion of the prior art cannot be
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`the basis for patentability when the differences would otherwise be obvious. See Ex parte
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`Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
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`In addition, as admits by applicant, it is known that the administration of steroids is
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`beneficial to suppress the inflammation caused by HCV resulting from intravenous use of
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`opioids of the patients. Thus, it would have been obvious to combine an opioid antagonist and a
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`steroidal anti—inflammatory agent in treating patient with opioid dependency.
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`Relevant Prior Art
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`The following relevant prior art is provided, but, not cited in the rejection:
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`1. FDA (non—patent literature, medication guide, Vivitrol (Naloxone for extended—release
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`injectable suspension, published July, 2013), showing that extended—release injectable naltrexone
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`is known.
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
`
`Page 11
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`2. Cooper et al. (non—patent literature, Neuroreport.; vol. 25(7), pp.521—526, May 7, 2014),
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`showing evidence from humans and animals suggests that anabolic—androgenic steroids (AAS)
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`may act in the brain via opioidergic mechanisms, and may potentiate effects of opioids.
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`No claim is allowed.
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`CONCLUSION
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`Applicant's amendment necessitated the new ground(s) of rejection presented in this
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`Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a).
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`Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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`A shortened statutory period for reply to this final action is set to expire THREE
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`MONTHS from the mailing date of this action. In the event a first reply is filed within TWO
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`MONTHS of the mailing date of this final action and the advisory action is not mailed until after
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`the end of the THREE—MONTH shortened statutory period, then the shortened statutory period
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`will expire on the date the advisory action is mailed, and any extension fee pursuant to 37
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`CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event,
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`however, will the statutory period for reply expire later than SIX MONTHS from the date of this
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`final action.
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`Contact Information
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to YANZHI ZHANG whose telephone number is (571)272—3117.
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`The examiner can normally be reached on Monday—Friday 8am—5pm.
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`

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`Application/Control Number: 15/999,517
`Art Unit: 1617
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`Page 12
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`Examiner interviews are available via telephone, in—person, and video conferencing using
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`a USPTO supplied web—based collaboration tool. To schedule an interview, applicant is
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`encouraged to use the USPTO Automated Interview Request (AIR) at
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`http://www.uspto.gov/interviewpractice.
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
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`supervisor, Johann Richter can be reached on 5712720646. The fax phone number for the
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`organization where this application or proceeding is assigned is 571—273—8300.
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`Information regarding the status of an application may be obtained from the Patent
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`Application Information Retrieval (PAIR) system. Status information for published applications
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`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
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`
`/YANZHI ZHANG/
`
`Primary Examiner, Art Unit 1617
`
`