UNITED STATES PATENT AND TRADEMARK OEEICE
`
`
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMIVIISS IONER FOR PATENTS
`P.O. Box 1450
`Alexandria. Virginia 22313-1450
`www.uspt0 gov
`
`APPLICATION NO.
`FILING DATE
`FIRST NAMED ENVENTOR
`ATTORNEY DOCKET NO.
`CONFIRMATION NO.
`
`14/523,650
`10/24/2014
`John C. BYRD
`FIR-88501
`1095
`
`13“”
`759°
`WW
`FOLEY HOAG. LLP (W/PIR) «
`PATENT GROUP, Seaport West
`TRAN, MY CHAU T
`155 SEAPORT BLVD
`BOSTON, MA 02210
`
`1629
`
`N O'IIEICATIOB DAl'E
`
`DELIVERY MODE
`
`04/22/2016
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address('es):
`
`Patent @ foleyhoagcoui
`pair_foleyhoag @firsttofile.com
`ABB VIE_PATENTS_AB T_PRK @ abeie .com
`
`PTOL-9OA (Rev. 04/07)
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`SAN EX 1021, Page 1
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`SAN EX 1021, Page 1
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`

`

`
`
`Applicant(s)
`Application No.
` 14/523,650 BYRD ET AL.
`
`
`AIA (First Inventorto File)
`Art Unit
`Examiner
`Office Action Summary
`
`
`1629MY-CHAU T. TRAN 5m”Yes
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`Application Papers
`
`10)I:I The specification is objected to by the Examiner.
`11)|Z| The drawing(s) filed on 10/24/2014 is/are: a)EI accepted or b)I:I 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)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. §119(a)-(d) or (f).
`Certified copies:
`
`b)|:| Some” c)I:l None of the:
`a)l:| All
`1.I:I Certified copies of the priority documents have been received.
`2.l:| Certified copies of the priority documents have been received in Application No.
`3.l:| 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.
`
`1) E Notice of References Cited (PTO-892)
`.
`.
`2) IX Information Disclosure Statement(s) (PTO/SB/OSa and/or PTO/SB/Osb)
`Paper No(s)/Mai| Date 03/03/2015.
`U S Patent and Trademark Olllce
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`3) D |merview Summary (PTO—413)
`Paper No(s)/Mai| Date.
`4 l:l O h
`_
`I
`‘ er- —-
`
`Part of Paper No./Mai| Date 20160416
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`SAN EX 1021, Page 2
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`
`
` Attachment(s)
`
`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 CFR1.136(a).
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received bythe Office later than three months after the mailing date of this communication, even it timely filed, may reduce any
`earned patent term adjustment See 37 CFR 1.704(b).
`
`In no event, however, may a reply be timely filed
`
`-
`-
`
`Status
`
`URI Responsive to communication(s) filed onW.
`El A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2b). This action is non-final.
`2a)|:l This action is FINAL.
`3)|:I An election was made by the applicant in response to a restriction requirement set forth during the interview on
`;the restriction requirement and election have been incorporated into this action.
`
`4)|:| Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under EX parte Quayle, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)XI CIaim(s)1-_20is/are pending in the application.
`5a) Of the above claim(s) 19 and 20 is/are withdrawn from consideration.
`
`6 |:l Claim s) _ is/are allowed.
`s M is/are rejected.
`—
`is/are objected to.
`
`
`) )
`
`)
`are subject to restriction and/or election requirement.
`9)|:| Claim(s
`* If any claims have been determined allowable, 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
`
`htt
`://\wtiw.useto. ov/ atents/init events/r) h/index.'s or send an inquiry to PPf-lfeedback-{Lbusptooov.
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`SAN EX 1021, Page 2
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 2
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`DETAILED ACTION
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`Application and Claims Status
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`1.
`
`Applicant’s response filed on 02/02/2016 is acknowledged and entered.
`
`2.
`
`Claims 1-20 were pending. No claims were amended, added, and/or cancelled.
`
`Therefore, claims 1-20 are currently pending.
`
`3.
`
`The present application, filed on or after March 16, 2013, is being examined under the
`
`first inventor to file provisions of the AIA.
`
`Election/Restrictions
`
`4.
`
`Applicant’s election without traverse of a species for a pharmaceutical composition in the
`
`reply filed on 02/02/2016 is acknowledged. The elected species is as follows: “Applicant
`
`respectfully elects without traverse Claims drawn to (R)-1-(3 -(4-amino-3 -(4-plzenoxyphenyl)-1H—
`
`pyrazolo[3,4-d]pyrimidin-] -yl)piperidin-I -yl)prop-2-en-one, also known as ibrutinib,
`
`
`
`represented by the structural formula
`
`5.
`
`Claims 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b)
`
`as being drawn to nonelected species, there being no allowable generic or linking claim.
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`SAN EX 1021, Page 3
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`SAN EX 1021, Page 3
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 3
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`Election was made Without traverse in the reply filed on 02/02/2016. Accordingly, claims 1—18
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`are under consideration in this Office Action.
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`Priority
`
`6.
`
`This instant application claims for domestic priority under 35 U.S.C. ll9(e) to four
`
`provisional applications. They are as follows: 61/895,981 that was filed on 10/25/2013;
`
`61/910,945 that was filed on 12/02/2013; 61/973,173 that was filed on 03/31/2014; and
`
`61/973,176 that was filed on 03/31/2014. Thus, the effective filing date of this instant application
`
`is 10/25/2013.
`
`Information Disclosure Statement
`
`7.
`
`The information disclosure statement (IDS) that was filed on 03/18/2016 has been
`
`reviewed, and the references that have been considered are initialed as recorded in PTO-1449
`
`forms.
`
`Claim Rejections - 35 USC § 112
`
`8.
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
`
`(a) IN GENERAL. The specification shall contain a written description of the invention,
`and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to
`enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to
`make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor
`of carrying out the invention.
`
`The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
`
`The specification shall contain a written description of the invention, and of the manner and
`process of making and using it, in such full, clear, concise, and exact terms as to enable any person
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`SAN EX 1021, Page 4
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 4
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`skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the
`same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
`
`9.
`
`Claims 1 and 3-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first
`
`paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject
`
`matter which was not described in the specification in such a way as to enable one skilled in the
`
`art to which it pertains, or with which it is most nearly connected, to make and/or use the
`
`invention. This is a scope of enablement rejection.
`
`First, claim 1 recites “A method ofpreventing the occurrence of graft versus host disease
`
`(GVHD) or reducing the severity of GVHD occurrence in a patient requiring cell
`
`transplantation, comprising administering to the patient a therapeutically effective amount of a
`
`compound of Formula (A) having the structure:
`
`a,» 52
`
`if‘ ”‘5‘;
`ii
`_
`£2
`SN“; “'8‘
`R;
`meuizi ($3:
`
`wherein: A is N; R1 is phenyl—O—
`
`phenyl or phenyl-S-phenyl; R2 and R3 are independently H,' R4 is L3-X—L4-G, wherein, L3 is
`
`optional, and when present is a bond, optionally substituted or unsubstituted alkyl, optionally
`
`substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted alkenyl, optionally
`
`substituted or unsubstituted alkynyl; X is optional, and when present is a bond, -O-, -C(=O)-, -S-
`
`, -S(=O)-, -S(=O)2-, -NH-, -NRg-, -NHC(0)-, -C(0)NH-, -NR9C(0)-, -C(0)NRg-, -S(=0)2NH-, -
`
`NHS(=0)2-, -S(=0)2NR9-, -NR95(=0)2-, -0C(O)NH-, -NHC(O)O-, -0C(0)NR9-, -NR9C(O)0-, -
`
`CH=NO-, -0N=CH-, -NR10C(0)N R10-, heteroaryl-, aryl-, -N R10C(=NR11)N R10-, -N
`
`R10C(=NR11)-, -C(=NR11)NR10-, -0C(=NR11)-, or -C(=NR11)0-; L4 is optional, and when present
`
`is a bond, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted
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`Application/Control Number: 14/523,650
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`Page 5
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`or unsubstituted aikenyl, substituted or unsubstituted alkynyi, substituted or unsubstituted aryl,
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`substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle; or L3, X and
`
`L4 taken together form a nitrogen containing heterocyclic ring; G is
`
`
`
`, wherein, R6, R7 and R3 are
`
`independently selected from among H, halogen, CN, OH, substituted or unsubstituted alkyl or
`
`substituted or unsubstituted heteroalkyl or substituted or unsubstituted cycloalkyl, substituted or
`
`unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
`
`heteroaiyl; each R9 is independently selected from among H, substituted or unsubstituted lower
`
`alkyl, and substituted or unsubstituted lower cycloalkyl; each R10 is independently H, substituted
`
`or unsubstituted lower alkyl, or substituted or unsubstituted lower cycloalkyl; or two R10 groups
`
`can togetherform a 5—, 6—, 7—, or 8—membered heterocyclic ring; or R10 and R11 can together
`
`form a 5 -, 6-, 7-, or 8-membered heterocyclic ring; or each R11 is independently selected from H
`
`or substituted or unsubstituted alkyl; or a pharmaceutically acceptable salt thereofi thereby
`
`preventing the occurrence of graft versus host disease (GVHD) or reducing the severity of
`
`GVHD occurrence in the patient”.
`
`It is interpreted that the instant claimed method encompasses
`
`both (a) a treatment method (i.e.) and (b) a method of prevention, i.e. “protecting” of any
`
`destruction prior to the onset “the occurrence of graft versus host disease (GVHD)”. Moreover,
`
`since the instant specification disclosures (see instant specification sections [0022]—[OO33]) is
`
`silent regarding the definition of the term “prevention”, this interpretation would be encompass
`
`by the definition (i.e. the plain meaning) for the term ‘prevention‘.
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 6
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`Here, claims 1 and 3—18 are rejected under 35 U.S.C. 112, first paragraph, because the
`
`specification, while being enabling for only a treatment method for ‘reducing the severity of
`
`GVHD occurrence in the patient’ (see instant specification sections: [0033] and [00173]-
`
`[00264]), does not reasonably provide enablement for a method of preventing ‘the occurrence of
`
`graft versus host disease (GVHD)’. The specification does not enable any person skilled in the
`
`art to which it pertains, or with which it is most nearly connected, to make and use the invention
`
`commensurate in scope with these claims.
`
`There are many factors to consider when determining whether there is sufficient evidence
`
`to support a determination that a disclosure does not satisfy the enablement requirement and
`
`whether any experimentation is “undue”. These factors include, but are not limited to: 1) The
`
`breadth of the claims; 2) The nature of the invention; 3) The state of the prior art; 4) The level of
`
`one of ordinary skill; 5) The level of predictability in the art; 6) The amount of direction
`
`provided by the inventor; 7) The presence or absence of working examples; and 8) The quantity
`
`of experimentation necessary needed to make or use the invention based on the disclosure. See
`
`In re Wands USPQ 2d 1400 (CAFC 1988).
`
`(1-2) The breadth of the claims and the nature of the invention:
`
`The claims are directed to the method for the prevention of ‘the occurrence of graft
`
`versus host disease (GVHD)’ using any of the compounds claimed by instant claim 1.
`
`The claims are broad enough to encompass both “protecting” of any destruction prior to
`
`any disease or disorder onset (e. g. PREVENTION) and during/subsequent to any disease or
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`disorder onset (e. g. TREATMENT) wherein the disease or disorder is ‘graft versus host disease
`
`(GVHDJ’.
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`SAN EX 1021, Page 7
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 7
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`Consequently, the nature of the invention cannot be fully determined because the
`
`invention has not been defined with particularity.
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`(3 and 5) The slate of the prior art and the level ofprediclability in the art:
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`Claims drawn to pharmaceuticals and methods of treatment generally require supporting
`
`data because of the unpredictability in biological responses to therapeutic treatments. This is
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`especially true for a preventive method, which meets with stricter scrutiny than treatments, since
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`additional controls and testing must be performed to insure prevention. The burden of enabling
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`the prevention of a disease or disorder; or its symptoms (i.e. the need for additional testing)
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`would be greater than that of enabling a treatment due to the need to screen those mammals (e. g.
`
`humans) susceptible to such diseases or disorders. And the difficulty of proof that the
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`administration of the drug composition was the agent that acted to prevent ‘graft versus host
`
`disease (GVHD)’. The specification does not provide guidance as to how one skilled in the art
`
`would go about screening those mammals susceptible to ‘grafi versus host disease (GVHD)’.
`
`Nor is guidance provided in the specification as to a specific protocol to be utilized in order to
`
`prove the efficacy of the presently claimed compound/composition, i.e. any of the compounds
`
`claimed by instant claims 1 and 3-6. Accordingly, undue experimentation is necessary to
`
`determine screening and testing protocols to demonstrate the efficacy of the presently claimed
`
`invention. Moreover, Magenau et al. disclose that there are many attempts to treat GVHD that
`
`have not been proven successful and that further is require in order to provide prevention and
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`immunity to GVHD (see e.g. pg. 200, right col., lines 22-38; British Journal of Haematology,
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`April 2016, Vol. 173, Issue 2, pp. 190—205).
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`SAN EX 1021, Page 8
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 8
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`For, the efficacy of a drug treatment in vivo faces unfavorable obstacles not present in
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`Vitro models. As such, in Vivo utility necessarily involves unpredictability with respect to
`
`physiological activity of an asserted process in humans. See discussion in Ex parle Kranz, 19
`
`USPQ2d 1216,1218-1219 (6/90). For example, drug delivery to the targeted area must survive
`
`the acidic environment of the stomach if administered orally. Additionally, the delivery of the
`
`drug across necessary cell surfaces in amounts needed to be efficacious, but not lethal to the
`
`organism, necessitates sensitive testing in order to adequately determine the proper human
`
`dosage. Additionally, there are no specific mammalian (e. g. human) genetic markers to enable
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`screening of those mammals genetically predisposed toward ‘graft versus host disease (GVHD)’.
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`Accordingly, undue experimentation is necessary to determine screening and testing
`
`protocols to demonstrate the efficacy of the presently claimed invention.
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`(4 ) The level of one of ordinary skill in the art:
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`The level of skill would be high, most likely at the Ph.D. level.
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`(6- 7) The amount of direction provided by the inventor and the existence of working examples:
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`The specification only provides support (i.e. examples) for the treatment methods for
`
`“reducing the severity of GVHD occurrence in the patient’ (see instant specification sections:
`
`[0033] and [00173]—[00264]). However, these examples would not be deemed by one of
`
`ordinary skill in the art to correlate or extrapolate toward the PREVENTION of the onset of
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`‘graft versus host disease (GVHD)’.
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`(8 ) The quantity of experimentation needed to make or use the invention based on the content of
`
`the disclosure:
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 9
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`As a result of the broad and unpredictable nature of the invention and the lack of specific
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`guidance from the specification, the Examiner contends that the quantity of experimentation
`
`needed to make and or use the invention would be great. Note that there must be sufficient
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`disclosure, either through illustrative examples or terminology, to teach those of ordinary skill
`
`how to make and use the invention as broadly as it is claimed. In re Vaeck, 947 F.2d 488,496 &
`
`n.23, 20 USPQ2d 1438, 1445 * n23 (Fed. Cir. 1991). In this case, Applicants have not provided
`
`any working examples that would teach this enormous genus that falls within a highly
`
`unpredictable art area. Therefore, it is deemed that further research of an unpredictable nature
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`would be necessary to make or use the invention as claimed. Thus, due to the inadequacies of
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`the instant disclosure one of ordinary skill would not have a reasonable expectation of success
`
`and the practice of the full scope of the invention would require undue experimentation.
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`Therefore based on the evidences as a whole regarding each of the above factors (e. g.
`
`factors 1-8), the specification, at the time the application was filed, does not satisfy the
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`enablement requirement for the instant claimed method of claims 1 and 3-18.
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`Claim Rejections - 35 USC § 102
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`10.
`
`In the event the determination of the status of the application as subject to AIA 35 USC.
`
`102 and 103 (or as subject to pre-AIA 35 USC. 102 and 103) is incorrect, any correction of the
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`statutory basis for the rejection will not be considered a new ground of rejection if the prior art
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`relied upon, and the rationale supporting the rejection, would be the same under either status.
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 10
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`11.
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`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the
`
`basis for the rejections under this section made in this Office action:
`
`A person shall be entitled to a patent unless 7
`
`(a)(l) the claimed invention was patented, described in a printed publication, or in public use, on sale or
`otherwise available to the public before the effective filing date of the claimed invention.
`
`(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for
`patent published or deemed published under section 122(b), in which the patent or application, as the
`case may be, names another inventor and was effectively filed before the effective filing date of the
`claimed invention
`
`12.
`
`Claims 1, 3-6, 11, 12, and 18 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being
`
`anticipated by Izumi et al. (US Patent Application Publication US 2015/0086507 A1; Effective
`
`Filing Date 0f04/11/2012).
`
`For claims 1, 3-6, I I, 12, and I8, Izumi et al. disclose pyrimidine—based inhibitors of
`
`Bruton’s tyrosine kinase (Btk) and methods of their use (see e. g. Abstract; sections: [0001],
`
`[0006]—[0007], [0009]—[0022], and [0065]—[0077]). In one embodiment, the pyrimidine—based
`
`inhibitor (Btk inhibitor) is a compound of structural Formula 111:
`
`
`
`, wherein: La
`
`is 0; Ar is an unsubstituted phenyl; Y is a 6—membered monocyclic nitrogen containing
`
`heterocyelic ring; Z is C(=O); R8 is H; R7 is H', and R6 is H (see e.g. sections: [0066]—[0077] and
`
`[OO86]—[0094]). The compound can be in a form suitable for oral use (see e.g. sections: [0110],
`
`[0117]—[0118], and [0122]—[0126]). This compound read on the elected species and instant
`
`claims 1, 3-6, and 18. In one embodiment, the method of administering the Btk inhibitor and
`
`SAN EX 1021, Page 11
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`Application/Control Number: 14/523,650
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`Page 11
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`hematopoietic stem and/or progenitor cell transplantation to a subject in order to enhance the
`
`success of bone marrow transplantation, and/or to aid in restoration of damaged organ tissue (see
`
`e.g. sections: [0007], [0009], [0129], [0131], and [0157]-[0172]). Although Izumi et a1. do not
`
`disclose treating the condition of ‘graft versus host disease (GVHD)’, this condition is art
`
`recognized to be directly associated with haematopoietic stem cell transplantation as evident by
`
`Magenau et a1. (see e. g. p g. 190, left col., lines 1-19; British Journal of Haematology, April
`
`2016, Vol. 173, Issue 2, pp. 190-205) and Min (see e.g. pg. 80; THE KOREAN JOURNAL OF
`
`HEMATOLOGY, June 2011, Vol. 46, No. 2, pp. 80—87). These disclosure would read on the
`
`instant claimed method of claims 1, 11, 12, and 18.
`
`Therefore, the compound and method of lzumi et al. do anticipate the instant claimed
`
`invention.
`
`13.
`
`Claims 1-18 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as anticipated by or, in the
`
`alternative, under 35 U.S.C. 103 as obvious over Izumi et al. (US Patent Application Publication
`
`US 2015/0086507 A1; Efi‘ective Filing Date 0f04/11/2012).
`
`For claims 1, 3-6, 11, 12, and 18, Izumi et al. disclose pyrimidine-based inhibitors of
`
`Bruton’s tyrosine kinase (Btk) and methods of their use (see 6. g. Abstract; sections: [0001],
`
`[0006]-[0007], [0009]-[0022], and [0065]-[0077]). In one embodiment, the pyrimidine-based
`
`SAN EX 1021, Page 12
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`Application/Control Number: 14/523,650
`Art Unit: 1629
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`Page 12
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`
`
`inhibitor (Btk inhibitor) is a compound of structural Formula Ill:
`
`
`*3
`, wherein: La
`
`is 0; Ar is an unsubstituted phenyl; Y is a 6-membered monocyclic nitrogen containing
`
`heterocyclic ring; Z is C(=O); R8 is 1-1; R7 is H; and R6 is 1-1 (see e.g. sections: [0066]—[0077] and
`
`[0086]-[0094]). The compound can be in a form suitable for oral use (see e.g. sections: [0110],
`
`[0117]-[0118], and [0122]-[0126]). This compound read on the elected species and instant
`
`claims 1, 3-6, and 18. In one embodiment, the method of administering the Btk inhibitor and
`
`hematopoietic stem and/or progenitor cell transplantation to a subject in order to enhance the
`
`success of bone marrow transplantation, and/or to aid in restoration of damaged organ tissue (see
`
`e.g. sections: [0007], [0009], [0129], [0131], and [0157]-[0172]). Although Izumi et a1. do not
`
`disclose treating the condition of “graft versus host disease (GVHD)’, this condition is art
`
`recognized to be directly associated with haematopoietic stem cell transplantation as evident by
`
`Magenau et a1. (see e. g. pg. 190, left col., lines 1—19; Britt's/z Journal of Haematology, April
`
`2016, Vol. 173, Issue 2, pp. 190-205) and Min (see e.g. pg. 80; THE KOREAN JOURNAL OF
`
`HEMATOLOGY, June 2011, Vol. 46, No. 2, pp. 80-87). These disclosure would read on the
`
`instant claimed method of claims 1, 11, 12, and 18.
`
`For claim 2, Izumi et a1. disclose pyrimidine-based inhibitors of Bruton’s tyrosine kinase
`
`(Btk) and methods of their use (see e.g. Abstract; sections: [0001], [0006]-[0007], [0009]-[0022],
`
`and [0065]-[0077]). In one embodiment, the pyrimidine-based inhibitor (Btk inhibitor) is a
`
`SAN EX 1021, Page 13
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`SAN EX 1021, Page 13
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`

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`Application/Control Number: 14/523,650
`Art Unit: 1629
`
`Page 13
`
`
`
`I ‘*-
`
`compound of structural Formula 111:
`
`, wherein: La is 0; Ar is an unsubstituted
`
`phenyl; Y is a 6-membered monocyclic nitrogen containing heterocyclic ring; Z is C(20); R3 is
`
`H; R7 is 1-1; and R6 is H (see e.g. sections: [0066]—[0077] and [0086]—[0094]). This compound
`
`read on the elected species and the compound of instant claim 2. In one embodiment, the
`
`method of administering the Btk inhibitor to a subject in order to enhance the success of bone
`
`marrow transplantation, and/or to aid in restoration of damaged organ tissue (see e.g. sections:
`
`[0007], [0009], [0129], [0131], and [0157]-[0172]). Although Izumi et a1. do not disclose
`
`treating the condition of “graft versus host disease (GVHD)’, this condition is art recognized to
`
`be directly associated with haematopoietic stem cell transplantation as evident by Magenau et a1.
`
`(see e.g. pg. 190, left col., lines 1—19; British Journal ofHaematology, April 2016, Vol. l73,
`
`Issue 2, pp. 190-205) and Min (see e.g. pg. 80; THE KOREAN JOURNAL OF HEMATOLOGY,
`
`June 2011, Vol. 46, N o. 2, pp. 80—87). These disclosure would read on the instant claimed
`
`method of claim 2.
`
`Alternatively, the claimed invention further differs from the prior art teachings only by the
`
`recitation of:
`
`For claims 2, 7-10 and 13-17, the claimed limitations of claims 2 and 7-10 (i.e. the
`
`specific type of GVHD conditions and disease of claim 10) and the claimed limitations of claims
`
`13-17 (i.e. the specific type of dosage and/0r dosing regimens) are interpreted as the functional
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`SAN EX 1021, Page 14
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`Application/Control Number: 14/523,650
`Art Unit: 1629
`
`Page 14
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`limitation for the instantly compound. The claimed invention appears to be the same or obvious
`
`variations of the reference teachings, absent a showing of unobvious differences. The office
`
`does not have the facilities and resources to provide the factual evidence needed in order to
`
`determine and/or compare the specific activities of the instant claimed compound versus the
`
`reference compound. In the absence of evidence to the contrary, the burden is upon the applicant
`
`to prove that the claimed compound is different from the one taught by prior art and to establish
`
`the patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex
`
`parte Gray 10 USPQ2d 1922(PTO Bd. Pat. App. & Int. 1989). As a result, the method of Izumi
`
`et a1. would still anticipate the presently claimed method since it meets all the structural
`
`limitation of the claimed compound of claims 1—6.
`
`Therefore, the compound and method of Izumi et a1. do anticipate the instant claimed
`
`invention.
`
`Double Patenting
`
`14.
`
`The nonstatutory double patenting rejection is based on a judicially created doctrine
`
`grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or
`
`improper timewise extension of the “right to exclude” granted by a patent and to prevent possible
`
`harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate
`
`where the claims at issue 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 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d
`
`SAN EX 1021, Page 15
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`SAN EX 1021, Page 15
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`

`

`Application/Control Number: 14/523,650
`Art Unit: 1629
`
`Page 15
`
`2010 (Fed. Cir. 1993); In re Inngi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van
`
`Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619
`
`(CCPA 1970); and In re Morington, 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) may
`
`be used to overcome an actual or provisional rejection based on a nonstatutory double patenting
`
`ground provided the reference application or patent either is shown to be commonly owned with
`
`this application, or claims an invention made as a result of activities undertaken within the scope
`
`of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR
`
`1.321(b).
`
`The USPTO intemet Web site contains terminal disclaimer forms which may be used.
`
`form should be used. A web—based eTerminal Disclaimer may be filled out completely online
`
`using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and
`
`approved immediately upon submission. For more information about eTerminal Disclaimers,
`
`15.
`
`Claims 1, 3-6, 12, and 15-18 are provisionally rejected on the ground of nonstatutory
`
`double patenting as being unpatentable over claims 1-5, 11, and 16-19 of copending Application
`
`No. 14/558,297 (US Patent Application Publication US 2015/0157634 A1; hereinafter refers to
`
`as Blazar et al.). Although the conflicting claims are not identical, they are not patentably
`
`distinct from each other because both the method of the instant claims 1, 3—6, and 15—18, and the
`
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`Application/Control Number: 14/523,650
`Art Unit: 1629
`
`Page 16
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`method of claims 1—5, 11, and 16—19 of Blazar et al. used a compound with similar structural
`
`features.
`
`14/523,650
`
`14/558,297
`
`1. A method of preventing the occurrence of
`graft versus host disease (GVHD) or
`reducing the severity of GVHD occurrence
`in a patient requiring cell transplantation,
`comprising administering to the patient a
`therapeutically effective amount of a
`compound of Formula (A) having the
`x.
`3
`film
`
`..\ KP?"
`
`8“
`
`1. A method of treating alloantibody driven
`chronic graft versus host disease (cGVHD)
`in a patient, comprising administering
`to a patient in need thereof a
`therapeutically effective amount of a
`compound of Formula (A) having the
`
`
`
`.
`.
`.
`:
`:- x}}‘ g
`structure: hm “ “W wherein: A is N; R1 is
`phenyl-O-phenyl or phenyl-S-phenyl;
`R2 and R3 are independently H; R4 is Lg-X-
`L4-G, wherein, L3 is optional, and when
`present is a bond, optionally substituted or
`unsubstituted alkyl, optionally substituted or
`unsubstituted cycloalkyl, optionally
`substituted or unsubstituted
`
`alkenyl, optionally substituted or
`unsubstituted alkynyl; X is optional, and
`when present is a bond, -O-, -C(=O)-, -S-, -
`S(=O)—, -S(=O)2-, -NH-, -NR9-, -NHC(O)-, -
`C(O)NH-, -NR9C(O)—, -C(O)NR9-, -
`S(=O)2NH-, -NHS(=O)2-, -S(=O)2NR9-, -
`NRgS(=O)2-, -OC(O)NH-, -NHC(O)O-, -
`OC(O)NR9-, -NRgC(O)O-, -CH=NO-, -
`
`ON=CH-, -NR10C(O)N R10-, heteroaryl-,
`aryl-, -N R10C(=NR11)N R10-, -N
`R10C(=NR11)-= -C(=NR11)NRio-, -
`OC(=NR11)-, or -C(=NR11)O-; L4 is
`
`optional, and when present is a bond,
`substituted or unsubstituted alkyl,
`substituted or unsubstituted cycloalkyl,
`substituted or unsubstituted alkenyl,
`substituted or unsubstituted
`
`.
`.
`2976:1131 1337) M2, 3;:
`1
`‘
`‘ whereln: A is N;
`structure:
`R1 is phenyl—O—phenyl or phenyl—S—phenyl;
`R2 and R3 are independently H; R4 is Lg-X-
`L4-G, wherein, L3 is optional, and when
`present is a bond, optionally substituted or
`unsubstituted alkyl, optionally substituted
`or unsubstituted cycloalkyl, optionally
`substituted or unsubstituted
`
`alkenyl, optionally substituted or
`unsubstituted alkynyl; X is optional, and
`when present is a bond, —O—, —C(=O)—, —S—, —
`S(=O)-, -S(=O)2-, -NH-, -NR9-, -NHC(O)-,
`-C(O)NH-, -NR9C(O)-, -C(O)NRg-, -
`S(=O)2NH-, -NHS(=O)2-, -S(=O)3NR9-, -
`NR9$(=O)2-, —OC(O)NH—, —NHC(O)O—, —
`OC(O)NR9-, -NR9C(O)O-, -CH=NO-, -
`
`ON=CH-, -NR10C(O)N R10-. heteroaryl-,
`aryl-, -N R10C(=NR11)N R103 -N
`R10C(=NR11)'» 'C(=NR11)NR10-, -
`OC(=NR11)-, or -C(=NR11)O-; L4 is
`optional, and when present is a bond,
`substituted or unsubstituted alkyl,
`substituted or unsubstituted cycloalkyl,
`substituted or unsubstituted alkenyl,
`
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`Application/Control Number: 14/523,650
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`
`
`Page 17
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`alkynyl, substituted or unsubstituted aryl,
`substituted or unsubstituted heteroaryl,
`substituted or unsubstituted heterocycle; or
`L3, X and L4 taken together form a nitrogen
`containing heterocyclic ring; G is
`
`
`
`
`, wherein, R6, R7 and R8 are independently
`selected from among H, halogen, CN, OH,
`substituted or unsubstituted alkyl or
`substituted or unsubstituted heteroalkyl or
`substituted or unsubstituted cycloalkyl,
`substituted or unsubstituted
`
`heterocycloal