PTO/AIA/14 {11-1 5)
`Approved for use through 04/3012017 , 0MB 0651-0032
`U.S. Patent .ind Trademark Offfce: u,s DEPARTMENT OF COMMERCE.
`U11tler me Pap!:rwork Redt1ctlon Act of 1995, nc, persons are required to res pond to a oollecrion l)finfcrr11~1fr)11 unlP.ss ii contains a 11Blid 0MB control nijmue1
`
`Application Data Sheet 37 CFR 1. 76
`
`Attorney Docket Number
`
`Application Number
`
`PAT058197-US-CIP02
`16/175261
`
`Title of Invention
`
`Stable, concentrated rad to nuclide complex solutions
`
`Authorization or Opt-Out of Authorization to Permit Access:
`
`When this Application Data Sheet is properly signed and filed with the application, applicant has provided written
`authority to permit a participating foreign intellectual property (IP) office access to ttle instant applicatron-as-filed (see
`paragraph A in subsection 1 below) and the European Patent Office (EPO) access to any search results from the tnstant
`application (see paragraph B in subsection 1 below).
`
`Should applicant choose nouo provide an authorization ldentrned in subsection 1 below, applicant must opt--out of the
`authorization by checking the corresponding box A or B or both in subsection 2 below.
`
`N.QTI;: This section of the Application Data Sheet is QN.L.Y. reviewed and processed with the lM.IlA~. filing of an
`application. Aft.er the initia l filing of an application, an Application Data Sheet cannot be used to provide or rescind
`authorization for access by a foreign IP offlce(s) . fnstead , Form PTO/SB/39 or PTO/SB/69 must be used as appropriate.
`
`1. Authorization to Permit Access by a Foreign Intellectual Property Office(s)
`
`A. PriorLty..Qocument Exchan..Q!L{PDX) - Unless box A in subsection 2 (opt-out of authorization) is checked, the
`undersigned hereby grants the USPTO authority to provide the European Patent Office (EPO) , the Japan Patent Office
`(JPO) . the Korean Intellectual Property Office (KIPO), the State Intellectual Property Office of the People's Republic of
`China (SIPO) , the World Intellectual Property Organization (WIPO) , ami any ottier foreign Intellectual property office
`participating with the USPTO in a bilateral or multilateral priority document exchange agreement in which a forelgn
`appllcation claiming priority to the instant patent application is filM., access to : (1) the instant patent application-as-filed
`and its related bibliographic data, (2) any foreign or domestic appHcation to which priority or benefit ls claimed by the
`instant application and its related bibliographic data, and (3} the date of filing of this Authorization. See 37 CFR 1.14(h)
`(1 ).
`
`B. Search Results f,:Q.m U.S. AJrnlication to EPO - Unless box B in subsection 2 (opt-out of authorization) is checked,
`the undersigned hereby grants the USPTO authority to provide ttle EPO access to the bibliographic data and search
`results from the .instant patent application when a European patent application claiming priority to the instant patent
`application is filed. See .37 CFR 1.14(tl)(2).
`
`The applicant is reminded that the EPO's Rule 141 (1) EPC (European Patent Convention) requires applicants to submit a
`copy of search results from the instant application without delay in a European patent application that claims priority to
`the instant application .
`
`2. Opt-Out of Authorizations to Permit Access by a Foreign Intellectual Property Office(s)
`
`A. Applicant DOES NOT authorize the USPTO to permit a participating fo re ign IP office access to the instant
`D application-as-filed. If this box is checked , the USPTO will not be providing a participating foreign IP office with
`any documents and information identified in subsection 1A above.
`
`B Applicant DOES NOT authorize the USPTO to transmit to the EPO any search results from the instant patent
`D application . lfthis box is checked, the USPTO will not be providing the EPO with search resl1lts from the instant
`application.
`NOTE: Once the application has published or is otherwise publicly available, the USPTO may provide access to the
`application in accordance with 37 CFR 1.14.
`
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`PTO/AIA/14 (11 -15)
`ApprovetJ for use through 04/3012017 . 0MB 0651-0032
`U .S. Patent an<l Traden,ark Offfce: u.s DEPARTMEN T OF COMMERCE
`U11tler me Papmwork Reducilon Act of 1995, no pe(S(ms are required to res pond lo a oollection ofinforrmt11)11 urllP.ss it contains a valid 0 MB control nurnlX'J .
`
`Application Data. Sheet 37 CFR 1.76
`
`Attorney Docket Number
`
`Application Number
`
`PAT058197,US-CIP02
`16/175261
`
`Title of Invention
`
`Stable, concentrated rad to nuclide complex solutions
`
`Applicant Information:
`
`Providing assignment information in this section does not substitute for compl iance with any requirement of part 3 of Title 37 of CFR
`to have an assignment recorded by the Office
`
`Applicant 1
`If the applicant is the inventor (or the rema ining joint inventor or inventors under 37 CFR 1 .45), this section should not be completed ,
`The information to be provided in this section is the name and address of the legal representative who 1s the applicant under 37 CFR
`1.43: or tile name and address of the assignee, person lo whom tile inventor is under an obligation to assign the Invention , or person
`who othe,wise shows sufficient proprietary interest in the matter who is the applicant under 37 CFR 1 46. If the applicant is an
`applicant under 37 CFR 1.46 (assignee , person to whom the inventor is obligated to assign, or person who otherwise shows suffic1ent
`proprietal)' intere st) together with one or more joint inventors, then the joint inventor or inventors who are also tne applicant should be
`identified in this section .
`!@Jit~@:wil
`lo Joint Inventor
`
`@ Assignee
`
`lo Legal Representative under 35 U.S.C. 117
`0 Person to whom the inventor is obligated to ass ign,
`10
`If applicant is the legal representative, indicate the authority to file the patent application, the inventor is:
`
`Person who shows sufficient proprietary Interest
`
`Name of the Deceased or Legally Incapacitated Inventor: I
`(gJ
`Organization Name I Advanced Accelerator Applications (Italy) Sri
`
`ff the Applicant is an Organization check here .
`
`Mailing Address Information For Applicant:
`
`I
`
`Address 1
`
`Address 2
`City
`Country' I IT
`
`Phone Number
`
`Email Address
`
`Via deli'lndustrla Prima Traversa
`
`Pozzilll
`
`pip_inbox.phchbs@novartis.com
`
`State/Province
`
`Postal Code
`
`Fax Number
`
`86077
`
`Additional Applicant Data may be generated within this form by selecting the Add button .
`
`Assignee Information including Non-Applicant Assignee Information:
`
`Providing assignment information in this section does not substi1ute for compliance with any requirement of part 3 of Title
`37 of CFR to have an assignment recorded by the omce .
`
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`PTOIAIA/14 (11 -15)
`ApprovetJ for use through 04/301201 '7 . 0MB 0651-0032
`U .S. Patent an<l Traden,ark Offfce: u.s DEPARTMEN T OF COMMERCE
`U11tler me Papmwork Reducilon Act of 1995, no persons are required to respond to a oollecrion ofinforrm111)11 urlless it cuntains a valid 0 MB control number .
`
`Application Data Sheet 37 CFR 1.76
`
`Attorney Docket Number
`
`PAT058197-US-CIP02
`
`Application Number
`
`16/175261
`
`Title of Invention
`
`Stable, concentrated rad to nuclide complex solutions
`
`Assignee 1
`
`Complete th is section if assignee information, including non-applicant assignee information, is desired to be included on t he patent
`appl1cation publication. An assignee-applfcant identified In the "Applicant Information" section will appear on the patent application
`publication as an applfcant. For an assignee-applicant, complete this section only if identlfication as an assignee Is also Cles fred on the
`patent application publication.
`
`lfthe Assignee or Non-Applicant Assignee is an Organization check here .
`
`(cid:143)
`
`Prefix
`
`Given Name
`
`Middle Name
`
`Family Name
`
`Suffix
`
`Mailing Address Information For Assignee including Non-Applicant Assignee:
`
`Address 1
`
`Address 2
`
`City
`
`Countryi
`
`I
`
`Phone Number
`
`Email Address
`
`State/Province
`
`Postal Code
`
`Fax Number
`
`Additional Assignee or Non-Applicant Assignee Data may be generated within this form by
`selecting the Add button .
`
`Signature:
`NOTE: This Application Data Sheet must be signed in accordance with 37 CFR 1 33{b) . However, if this Application
`Data Sheet is submitted with the JWTJA!.. filing of the application ~JJ_g either box A or Bis !J0t checked in
`subsection 2 of the "Authorization or Opt-Out of Authorization to Permit Access" section, then this form must
`also be signed in accordance with 37 CFR 1.14(c).
`This Application Data Sheet must be signed by a patent practitioner if one or more of the applicants is a juristic
`entity (e .g., corporation or association). If the applicant is two or more jofnt inventors, this form must be signed by a
`patent praLiitioner, .fill joint inventors who are the applicant, or one or more joint inventor-applicants who have been given
`power of attorney {e.g , see US PTO Form PTO/A IA/81) on behalf of .rul Joint inventor-applicants.
`See 37 CFR 1.4(d) for the manner of making signatures and certifications .
`
`Signature
`
`/Lian Ouyang/
`
`First Name
`
`Lian
`
`I Last Name I Ouyang
`
`Pate (YYYY- MM-DD)
`
`2019-05-13
`
`Registration Number
`
`69,254
`
`Additional Signature may be generated within this form by selecting the Add button.
`
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`PTO/AIA/14 {11-15)
`Approved for use through 04/3012017, OMl3 0651-0032
`U .S. Patent .ind Trademark omce: u,s DEPARTMENT OF COMMERCE.
`U11tler me Papmwork Redtrctlon Act of 1995, nc, persons are required to .-espond to a oollecrion l)f inforr11~1f1) n unless it contains.;;; valid 0MB control numt)er
`
`Application Data Sheet 37 CFR 1. 76
`
`Attorney Docket Number
`
`PAT058197-US-C IP02
`
`Application Number
`
`16/175261
`
`Title of Invention
`
`Stable, concentrated rad to nuclide complex solutions
`
`This collection of information is required by 37 CFR 1.76. The information is requ ired to obtain or retain a benefit by the public which
`is t o me (and by tile USPTO lo process) an application. Confldentality Is governed by 35 U .S.C. 122 and 37 CFR 1.14 Thrs
`collection is estimated to take 23 mlnutes to complete , Including gathering, preparing , and submitting the completed application data
`sheet form to the USPTO. Time will vary depe(lding upon the individual case. Any comments on the amount of time you requ ire to
`complete th is fo(m and/or suggestions for reducing this burden , should be sent to the Chief lnformatlon Officer, U .S. Patent and
`Trademark Office, U .S. Department of Commerce, P.O. Box 1450, Alexandria, VA 22313-1450 DO NOT SEND FEES OR
`COMPLETED FORMS TO THIS ADDRESS , SEND TO: Commissioner for Patents, P.O. Box 1450, Ale.xandria, VA 22313 -1450.
`
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`Privacy Act Statement
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`The Privacy Act of 1974 (P.L. 93-5791 requires that you be given certain information in con11ectio11 with your subrnlssion of the att,1ched fo1m related lo a patent
`application or patent. Accordingly, pursuant ,o the requlrE<rnenls of the An, please be advised that: (1) the general authority for the collt>ction of this 11,formatlon
`is 35 U 5 C. 2(b)(2); (2)fur nfsh,ng of the information solicited is volunta ry; and (3l the prir1cip;; I purposl:!' ror whkh th!:!' irifo1rnation is used by the U.S. Patl:!'nt and
`Trademark omce is to process and/or examine your submisslo;) related to a patent application or patent. If you do not furnish the reque~ted lnforrnation, the U.$
`Patent and Trademark Office may not be able to process and/or exarr1ine your submbsion, which may restJlt in termination or proceedings or abandonment of
`the application 01 expiraticin of the patent
`
`n1e information provided by )IOU in 1his form will be subJect to thefollowlng routille ,Jses·
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`The infonnatiot1 on this form will be treated confidentialiy to lhe extentallowl!d under the Freedom of lnfom1alio11 Act (5 U.5.C. 5S2) and the Privacy
`Act (5 USC. 552a). Records from this syste111 of records may be disclosed to the Department of Justice to determ ine whethet the FrP.edorn or
`lnforroation Act requires disclosure oftliese records.
`
`2. A record 1'rorn this syste11"1 of records may be disclosed, as a routine use, in the course of presenting evidence to a court, magistrate, or administrative
`tribunal, including disclosures to opposing toumeJ in the course of settlement ne<Joliations,
`
`3 A record in this system of recotd!i may be disclosed, as a routine use, to a Member o-f Congress submitting a request in,•olving an individual, lo whom
`the record pertdins, when the individ ual has req uested assistance from the Member with r!.'spect to the subject matter of the record .
`
`.el. A record ln thi~ system of records may be disdosed, as a 101.Jtlne use, 10 .-. conlrac.tor oi the Agency having need for the information in 01der to pe1fo1m
`a contract. Recipients of inforrnation ,hail be required to comply with the requirements of the Prfvac.y Act of 1974, ilS amended, p,1rsu,inl to 5 U.S.C.
`552a(ml.
`
`5, A reco rd related to dn lntematlonal Applkation liled under the ?a tent CooperatfonTreatyin this system of records may be disclosed, a a ioutine use,
`ta the International Bureau of the World 111tellec;tual Properly O1ganizalion, pursuant lo the Patent Cooperatio11Trealy.
`
`6. A reco rd in this system of records may be disclosed, as ii routine use, lo another federa l agency for purposes of National Secutity review (35 U.S.C. 181)
`ar,d fot review pursuant to the Atomic Energy Act(,12 U S.C. 218(c.J),
`
`7, A re.::ord fl'om this systern of records may be disclosed, as a routine 1.Jse, to the Administrator, Gener<'!! Services, or his/her deslgnee, during an
`impeclfon of records conducted by GSA as part of that agency's responsibility lo 1ecomrne11d improvements [n ,ecords rndnagement practlces and
`p1ograms, under authority of 44 U.5.C. 2904 and 2906. Such disclosure shall be made in accordance With the GSA regulations governing inspection of
`reco1ds for this purpose, and any other 1elevant (i.e., GSA or Commerce) directive. Such disclosure shall not be used to n,ake detenninatiom about
`Individuals,
`
`8. A record from this sys tern or record$ may be disclosed, as a routine 1.Jse, to the public after either publication of the application pursuant to 35 U.S.C.
`122(b) or issuance of a patent pw suant co 35 IJ.S.C. 151 . Further, a record rnay be disclosed, £ubject to the limitations of 37 CFR 1. 14, as a routtne use.
`to the pl.lblic if the record was filed in an application which became abandoned or fn which the proceedings were lenninated and which application is
`referenced by eltt1et a published ilppllcation, an application open to public Inspections or an issued patent.
`
`9. A record f, om thi~ system or records may be disclosed, as a routine use, to a Federal, Statt>, 01 local law enforcement agency, If the \JSPTO becomes
`awa1e <.>fa violc1ti<.><1 or potenllal violation of law lll regulation.
`
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`PTO/S8108a (02-18)
`Doc code. IDS
`Approved ror use through 11/30/2020_ 0MB 0651-0031
`Doc description; lhformation Disclosure Statement (IDS) Filed
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act or 1995, no pe~s are required to respond to a collection of infotma1ion unless ~ contains a valid 0MB control number.
`
`Application Number
`
`~6175261
`
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`( Not for submission under 37 CFR 1.99)
`
`Filing Date
`
`~018-10-30
`
`First Named Inventor I ~e Palo. Francesco
`
`Art Unit
`
`Examiner Name
`
`1618
`
`I Perreira. Melissa Jean
`
`Attorney Docket Number
`
`PAT058197-US-CIP02
`
`-
`
`u _s_PATENTS
`
`I Remove I
`
`Examiner Cite
`Initial
`No
`
`Patent Number
`
`Kind
`Code1 Issue Date
`
`Name of Patentee or Applicant
`of cited Document
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`Pages,Columns,Lines where
`Relevant Passages or Relevant
`Figures Appear
`
`1
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`If you wish to add additional U.S. Patent citation information please cLick the Add button.
`
`U.S.PATENT APPLICATION PUBLICATIONS
`
`I
`I Add
`I Remove I
`
`Examiner
`Initial"
`
`Cite No
`
`Publication
`Number
`
`Kind Publication
`Code1 Date
`
`Name of Patentee or Applicant
`of cited Document
`
`Pages,Columns,Lines where
`Relevant Passages or Relevant
`Figures Appear
`
`1
`
`I
`If you wish to add additional U.S. Published Application citation information please click the Add button Add
`!Remove!
`FOREIGN PATENT DOCUMENTS
`
`Examiner Cite Foreign Document
`No Number3
`Initial"
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`Country
`Code2j
`
`Kind Publication
`Code4 Date
`
`Name of Patentee or
`Applicant of cited
`Document
`
`Pages,Columns,Lines
`where Relevant
`Passages or Relevant
`Figures Appear
`
`TS
`
`1
`
`~018081860
`
`WO
`
`A1
`
`2018-05-11
`
`Clarity Pharmaceuticals
`DTYLTD
`
`If you wish to add addit1onal Foreign Patent Document citation information please click the Add button I Add I
`!Remove!
`NON-PA TENT LITERATURE DOCUMENTS
`
`Examiner Cite
`Initials* No
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`Include name of the author (in CAPITAL LETTERS), title of the article (when appropriate), title of the item
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`
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`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`( Not for submission under 37 CFR 1.99)
`
`Application Number
`
`16175261
`
`Filing Date
`
`2018-10-30
`
`First Named Inventor I de Palo, Francesco
`
`Art Unit
`
`Examiner Name
`
`1618
`
`I Perreira, Melissa Jean
`
`Attorney Docket Number
`
`PAT058197-US-CIP02
`
`1
`
`If you wish to add additional non-patent literature document citation information please click the Add button I Add I
`EXAMINER SIGNATURE
`Examiner Signature II
`I Date Considered 11
`
`" EXAMINER: Initial if reference considered , whether or not citation is in conformance with MPEP 609. Draw line through a
`citation if not in conformance and not considered . Include copy of this form with next communication to applicant.
`
`1 See Kind Codes of USPTO Patent Documents at www.USPTO. GOV or MPEP 901 .04. 2 Enter office that issued the document, by the two-letter code (WIPO
`Standard ST.3). 3 For Japanese patent documents, -!tie indicalion of the year of the reign of the Emperor must precede the serial number of U1e patent documenl
`~ Kind of document by the appropriate symbols as indicated on the document under WIPO Standard ST.16 if possible. ~ Applicant is to place a check mark here~
`English language translation ,s attached.
`
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`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`( Not for submission under 37 CFR 1.99)
`
`Application Number
`
`16175261
`
`Filing Date
`
`2018-10-30
`
`First Named Inventor I de Palo, Francesco
`
`Art Unit
`
`Examiner Name
`
`1618
`
`I Perreira, Melissa Jean
`
`Attorney Docket Number
`
`PAT058197-US-CIP02
`
`Please see 37 CFR 1.97 and 1.98 to make the appropriate selection(s):
`
`CERTIFICATION STATEMENT
`
`That each item of information contained in the information disclosure statement was first cited in any communication
`from a foreign patent office in a counterpart foreign application not more than three months prior to the filing of the
`information disclosure statement. See 37 CFR 1.97(e)(1 ).
`
`OR
`
`That no item of information contained in the information disclosure statement was cited in a communication from a
`foreign patent office in a counterpart foreign application, and, to the knowledge of the person signing the certification
`after making reasonable inquiry, no item of information contained in the information disclosure statement was known to
`D any individual designated in 37 CFR 1.56(c) more than three months prior to the filing of the information disclosure
`statement. See 37 CFR 1.97(e)(2).
`
`See attached certification statement.
`X The fee set forth in 37 CFR 1.17 (p) has been submitted herewith.
`A certification statement is not submitted herewith.
`
`SIGNATURE
`A signature of the applicant or representative is required in accordance with CFR 1.33, 10.18. Please see CFR 1.4(d) for the
`form of the signature.
`
`Signature
`
`Name/Print
`
`/Lian Ouyang/
`
`Lian Ouyang
`
`Date (YYYY-MM-DD)
`
`2019--05-13
`
`Registration Number
`
`~9.254
`
`This collection of information is required by 37 CFR 1.97 and 1.98. The information is required to obtain or retain a benefit by the
`public which is to file (and by the USPTO to process) an app11cation. Confidentiality is governed by 35 U.S.C. 122 and 37 CFR
`1.14. This collection is estimated to take 1 hour to complete, including gathering, preparing and submitting the completed
`application form to the USPTO. Time will vary depending upon the individual case. Any comments on the amount of time you
`require to complete this form and/or suggestions for reduclng this burden, should be sent to the Chief Information Officer, U.S.
`Patent and Trademark Office, U.S. Department of Commerce, P.O. Box 1450, Alexandria, VA 22313~1450. DO NOT SEND
`FEES OR COMPLETED FORMS TO THIS ADDRESS. SEND TO: Commissioner for Patents, P.O. Box 1450, Alexandria,
`VA 22313-1450.
`
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`Privacy Act Statement
`
`The Privacy Act of 1974 (P.L. 93-579) requires that you be given certain information in connection with your submission of the
`attached form related to a patent application or patent. Accordingly, pursuant to the requirements of the Act, please be advised
`that: (1) the general authority for the collection of this information is 35 U.S.C. 2(b)(2); (2) furnishing of the information solicited
`is voluntary; and (3) the principal purpose for which the information is used by the U.S. Patent and Trademark Office is to
`process and/or examine your submission related to a patent application or patent. If you do not furnish the requested
`information, the U.S. Patent and Trademark Office may not be able to process and/or examine your submission, which may
`result in termination of proceedings or abandonment of the application or expiration of the patent.
`
`The information provided by you in this form will be subject to the following routine uses:
`
`1.
`
`2 .
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`The information on this form will be treated confidentially to the extent allowed under the Freedom of Information Act
`(5 U.S.C. 552) and the Privacy Act (5 U.S.C. 552a). Records from this system of records may be disclosed to the
`Department of Justice to determine whether the Freedom of Information Act requires disclosure of these records.
`
`A record from this system of records may be disclosed, as a routine use, in the course of presenting evidence to a
`court, magistrate, or administrative tribunal, including disclosures to opposing counsel in the course of settlement
`negotiations.
`
`A record in this system of records may be disclosed, as a routine use, to a Member of Congress submitting a
`request involving an individual, to whom the record pertains, when the individual has requested assistance from the
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`
`A record in this system of records may be disclosed, as a routine use, to a contractor of the Agency having need for
`the information in order to perform a contract. Recipients of information shall be required to comply with the
`requirements of the Privacy Act of 1974, as amended, pursuant to 5 U.S.C. 552a(m).
`
`A record related to an International Application filed under the Patent Cooperation Treaty in this system of records
`may be disclosed , as a routine use, to the International Bureau of the World Intellectual Property Organization, pursuant
`to the Patent Cooperation Treaty.
`
`A record in this system of records may be disclosed, as a routine use, to another federal agency for purposes of
`National Security review (35 U.S.C. 181) and for review pursuant to the Atomic Energy Act (42 U.S.C . 218(c)).
`
`A record from this system of records may be disclosed, as a routine use, to the Administrator, General Services, or
`his/her designee, during an inspection of records conducted by GSA as part of that agency's responsibility to
`recommend improvements in records management practices and programs, under authority of 44 U.S.C. 2904 and
`2906. Such disclosure shall be made in accordance with the GSA regulations governing inspection of records for this
`purpose, and any other relevant (i.e., GSA or Commerce) directive. Such disclosure shall not be used to make
`determinations about individuals.
`
`8.
`
`A record from this system of records may be disclosed , as a routine use, to the public after either publication of
`the application pursuant to 35 U.S.C. 122(b) or issuance of a patent pursuant to 35 U.S.C. 151 . Further, a record
`may be disclosed , subject to the limitations of 37 CFR 1.14, as a routine use, to the public if the record was filed in
`an application which became abandoned or in which the proceedings were terminated and which application is
`referenced by either a published application, an application open to public inspections or an issued patent.
`
`9.
`
`A record from this system of records may be disclosed, as a routine use, to a Federal , State, or local law
`enforcement agency, it the USPTO becomes aware of a violation or potential violation of law or regulation .
`
`EFS Web 2.1.18
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`IOJ\AL APPi.iC '11ON PutU .ISHim
`(12) INTER Pt-
`( 19) World Jn teUectual Property
`Organization
`
`. ' Dli:R THE P TE T COOPERATIO: T IU: ATY (J>CT)
`
`International Bureau d 11111111111111 II 11111111111 lllll 1111111111 11111 lllll 11111 IIUI 1111111111 1111 1111111111111111111
`
`(43) lotl1roaHooal Publicalion Date
`11 May 2018 (I 1.05.2018)
`
`WIPO I PCT
`
`(10) International Publication umber
`WO 2018/081860 Al
`
`-
`
`--
`= = = = ---
`--= -
`--___. ----
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`---
`
`(51) loteroatlooal Patent Classification:
`A.6/ K 51/08 (2006_01)
`(21) lotcroatioou1 Applica1ioo . umber:
`PCT/AU201 7/051205
`
`(22) lntcrnatic,nal Filing Dute:
`02 N vember 2017 (02. 1 J .2017)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(30) Priority Uata:
`2016904515
`
`04 November 2016 (1>4. 11.2016) J\U
`
`(71) Applicant: Cl.AIUTY PHARMACEUTICAL PTY
`LTD IAU/ AlJJ: Natio11al l1111ov.11 ion Cc111re, 4 Co111wallis
`treet. Evcle.igh., New · 1uth W a.lcs 2015 (AU .
`
`(72) roveotors: HAJ~RIS, Matthew .J(lhn; 19 1l1e Avenue.
`lhUltors llill, New S u1.h Wale ~ 2 110 (AU) . VA.:."'i DA.\IL
`l•:llen Marianne; 4 l/'.!.77-283 Canterh111y Road , Canter(cid:173)
`bury. New South Wa le:. 2193 (AU). ,TI-,FFER • Ch1Jr(cid:173)
`m11ine illrie; 3/283 Ula<.ls1one RoaJ.. Dutton Park, Queens(cid:173)
`land 4102{AU) .
`
`(74)
`
`gent: D VCES COLUSO'.'/ CA VE PTY L'fD; Level
`15/ 1 Nic.bo!son Street, Melboumc, Vic1nria 3000 (AU).
`
`(81) Desi •onted Stntcs (unle s other wise indicated . ./or e,:el)'
`l.iml uf nmional protection nvai/uble): A£. AG. AL, AM.,
`AO, AT. AU, AZ, BA, BB. BG. BH. BN, HR. BW, BY, BZ.
`CA. CILCL,CN . CO, CR,CU , CZ. 1)13, DJ, DK. DM, 00,
`DZ, EC, EE. EG, E ·, FL ,B, ,D. GI: , 0 1-1,
`iM, ff. H.N,
`HR. HU , JI), IL, IN, IR, IS, JO. JP, KJ--', KG. KH, KN , KP,
`KR, KW. KZ , LA, LC, LK,LR, L , LU, LY , MA, MD, M E,
`MG , MK, MN. MW. MX, MY. MZ, NA, NU, NL, NO. NZ..
`OM , PA, PI!, PG. Pl I. PL, PT. QA, RO , R. ·• RU, RW. ' A,
`, . ,'K. . L.SM, ST. S . 'Y, TH. TJ. TM. TN.
`C, P.SE,
`TR, TT, TZ. UA. U<i. US. Z, VC, VN, ZJ\. ZM, ZW .
`
`(84) De ·ignatcd Srntci; /unless oJ/ierwise indicated . .for every,
`1.i1r(/ r>.f ref!)tlnol [)ra l1tc:ri1m availuhle): AR.IP
`(TIW, Gil ,
`GM. KE, LR, LS. MW, MZ. NA, RW. SD, SL, T. SZ, TZ.
`UG, ZM, Z\\I). Eu.ra~ian M, AZ. BY, KO. KZ, RU, TJ.
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`.EE, ES, fl, FR. B, ,R. IIR rru. m, I.. IT. LT, LU. LV .
`MC..:, MK, MT, NL. NO. PL. PT. R • RS, Se_ SL K, SM...
`TR). OAPT (OF. OJ. CF. CG. er. CM. GA. ON . GQ. GW.
`KM. ML. MR, NE. N TD. TG).
`
`(54) Title: FORMULATION. F R RADIOTHERAPY AND OT GNO TIC IMA TNG
`
`Figure 1
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`
`(57) Abstract: Tbc i,rc cnt invention rcl1.1tc.; to fonmLlations of radiol.nhclle<.l compound~ 1bm urc n fusc in rad.i otb..:rnpy and diagnostic
`imaging.
`
`(Continued on 11t:::>:1 page]
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`WO 2018/081860 Al llllll llllllll 1111111111111 IIIII IIIII IIII Ill Ill lllll lllll lllll llllllllll 1111 1111111 11111111 1111
`
`Published:
`will, i11ternr11iv11t1f . earch reporl (An. 11(3)/
`before Jh e e:rpir111io11 c1r 1/,,t litllL' limit _{(Ir amemling the
`claim and la he republished i11
`t/1c ewm/ of recoipt (1_(
`ame11dme11ts (Ru le 48.'!(lt))
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`WO 2018/081860
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`PCT/AU2017/05l205
`
`Formulations tor Radiotherapy and Diagnostic Imaging
`
`Field
`The present invention relates to formulations of radiolabelled compounds that are of use in
`radiotherapy and diagnostic imaging.
`
`Background
`Radiolabelled compounds or ligands may be used as radiopharmaceuticals in applications
`such as radiotherapy or diagnostic imaging. Of particular use, a re radiolabelled compounds
`that show some propensity for selectively targeting a particular site in vivo, (for example, a
`particular receptor), and subsequently delivering the radioisotope to the desired site of
`action. This requires that the ligand comprises a component to complex the radioisotope and
`a further component to target the desired site.
`
`One of the known problems associated with such a ligand is the prematu re dissociation of
`the radioisotope prior to the arrival of the ligand-radioisotope complex at the site of action.
`Not only does this reduce the efficacy of the complex, but the loss of the radioisotope to
`areas where radiotherapeutic effects are not intended, may result in adverse consequences.
`
`Dissociation of the radioisotope from the ligand may occur as a result of transchelation,
`where the radioisotope transfers to another biological ligand in vivo. Again, this leads to a
`reduced therapeutic effect and also delivery of a radioisotope to areas where treatment is
`not required.
`
`The ligand to be radiolabelled and the radioisotope are usually stored and transported to the
`patient in separate containers to minimise the above problems relating to dissociation prior
`to administration. The ligand may be transported as a lyophilized powder at reduced
`temperatures in order to prolong stability of the compound. The radioisotope can then be
`combined with the ligand to form the radiopharmaceutical, just prior to administration,
`which can serve to minimise dissociation of the radioisotope prior to the complex reaching
`the site of action.
`
`Another problem associated with radiolabelled compounds is that the use of a radioisotope
`may result in radiolysis, or destruction of the ligand. As a radioisotope undergoes
`spontaneous decay and subsequent release of radiation, this energy may be sufficient to
`induce cleavage of bonds and cause subsequent destruction of the ligand. In addition to the
`reduced efficacy of the radiopharmaceutical, release of the rad ioisotope also occurs,
`resulting in the delivery of radiation to unwanted sites.
`
`As many radiopharmaceuticals are designed to be administered parenterally✓ i.e. non-orally
`and usually as a solution, the ligand itself must be soluble in a pharmaceutically acceptable
`solvent or carrier. As is known in the art, the solubility of a particular compound in any
`given solvent may be unpredictable. Although the solubility of a particular compound in a
`particular solvent may be known, the solubility of an analogue of the compound in a
`different solvent system may be quite different. This then presents difficulties to one
`seeking to develop a formulation of a compound and especially a pharmaceutically
`acceptable injectable formulation.
`
`Pharmaceutical formulations typically Include one or more excipients that affect the
`compound in some way, such as the enhancement of solubility of the compound or
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`PCT/AU2017/051205
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`increasing stability of the compound while in solution. Alternatively, additional excipients
`may be used to provide other features to the formulation, such as preservatives, buffers and
`the like.
`
`While many thousands of formulations of ligand-radioisotope complexes have been
`documented, there is no expectation that the excipients used in such formulations would
`provide the required solubility and bioavailability of any newly developed complex.
`Furthermore, one cannot expect that a particular combination of excipie