ATTORNEY DOCKET NO. 23278.2.US.9
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`) Group-Art Unit: Not Yet Assigned --
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`) Examiner: Not Yet Assigned
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`) Confirmation No.: Not Yet Assigned
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`)
`
`In re Application of:
`
`Giorgio CALDERARI et al.
`
`Application No.: Not Yet Assigned
`
`Continuation of U.S. Application No.
`13/901,437
`
`Filed: Herewith
`
`For: LIQUID PHARMACEUTICAL
`FORMULATIONS OF
`PALONOSETRON
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
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`PRELIMINARY AMENDMENT AND CHOICE OF LAW
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`Prior to the examination of the above application, please amend this application
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`as follows:
`
`. Amendments to the Specification are included in this paper.
`
`Amendments to the Claims are reflected in the listing of claims in this paper.
`
`Remarks/Arguments follow the amendment sections of this paper.
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`5582030v1
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`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`Helsinn Healthcare S.A., et al.
`U.S. Patent No. 9,(cid:20)(cid:26)(cid:22),(cid:28)(cid:23)(cid:21)
`Reddy Exhibit 1020
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`Exh. 1020
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`

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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 2 of 11
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`AMENDMENTS TO THE SPECIFICATION:
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`Please amend the specification as follows:
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`Please delete the paragraph at page 1, line 2 and replace it with the following
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`new paragraph:
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`This is a continuation of U.S.S.N. 13/901,437, filed May 23, 2013, which is a
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`continuation-in-part of U.S.S.N. 13/087,012 filed April 14, 2011, which is a continuation
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`of U.S.S.N. 11/186,311 filed July 21, 2005 (now U.S. Patent No. 7,947,724), which is a
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`continuation of PCT/EP04/000888, filed January 30, 2004, which claims priority to U.S.
`
`Provisional Application 60/444,351, filed January 30, 2003. The content of these
`
`applications is incorporated herein by reference.
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 3 of 11
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`AMENDMENTS TO THE CLAIMS:
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`This listing of claims will replace all prior versions and listings of claims in the
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`application:
`
`1-9.
`
`(Canceled)
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`10.
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`(New) A pharmaceutical single-use, unit-dose formulation for intravenous
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`administration to a human to reduce the likelihood of cancer chemotherapy-induced
`
`nausea and vomiting, comprising a 5 ml sterile aqueous isotonic solution buffered at a
`
`pH of 5.0 ± 0.5, said solution comprising:
`
`palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its
`
`free base;
`
`optionally a chelating agent; and
`
`from 10 mg/ml to 80 mg/ml mannitol,
`
`wherein said
`
`formulation
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`is stable at 24 months when stored at room
`
`temperature.
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`11.
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`(New) The pharmaceutical formulation of claim 10, wherein said mannitol
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`is in an amount of 41.5 mg/ml.
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`12.
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`(New) The pharmaceutical formulation of claim 10, wherein said solution
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`further comprises a chelating agent.
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`13.
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`(New) The pharmaceutical formulation of claim 12, wherein said chelating
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`agent is EDT A.
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 4 of 11
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`14.
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`(New) The pharmaceutical formulation of claim 13, wherein said EDTA is
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`in an amount of from 0.005 mg/ml to 1.0 mg/ml.
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`15.
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`(New) The pharmaceutical formulation of claim 14, wherein said EDTA is
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`in an amount of 0.5 mg/ml.
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`16.
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`(New) The pharmaceutical formulation of claim 10, wherein said solution
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`further comprises a citrate buffer.
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`17.
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`(New) The pharmaceutical formulation of claim 16, wherein said citrate
`
`buffer is at a concentration of 20 millimolar.
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`18.
`
`(New) A pharmaceutical single-use, unit-dose formulation for intravenous
`
`administration to a human to reduce the likelihood of cancer chemotherapy-induced
`
`nausea and vomiting, comprising a 5 ml sterile aqueous isotonic solution buffered at a
`
`pH of 5.0 ± 0.5, said solution comprising:
`
`palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its
`
`free base;
`
`optionally a chelating agent; and
`
`from 1 0 mg/ml to 80 mg/ml mannitol,
`
`wherein said
`
`formulation
`
`is stable at 18 months when stored at room
`
`temperature.
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 5 of 11
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`I.
`
`Status of the Specification and Claims
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`REMARKS
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`The specification has been amended to update the priority information of this
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`new continuing application.
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`Upon entry of this amendment, claims 10-18 are currently pending in this
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`application. Claims 1-9 of the copending parent continuation-in-part (CIP) application
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`are canceled without prejudice or disclaimer. New claims 10-18 find support under 35
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`U.S.C. § 112 in the provisional application, 60/444,351 ("the '351 Application") filed
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`January 30, 2003, of the copending parent CIP (see Domestic Benefit/National Stage
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`Information in the accompanying Application Data Sheet, which establishes a chain of
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`copendency and specific reference from
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`the copending CIP back to the
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`'351
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`Application). Thus, claims 1 0-18 have an effective filing date (EFD) prior to March 16,
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`2013.
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`II. Choice of Law
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`This application falls under both transition provisions 3(n)(1) and 3(n)(2)1 of the
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`America Invents Act (AlA) because claims 10-18 have an EFD prior to March 16, 2013,
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`1 SEC. 3(n)(1 ): "Except as otherwise provided in this section, the amendments made by
`this section shall take effect upon the expiration of the 18-month period beginning on
`the date of the enactment of this Act [March 16, 2013], and shall apply to any
`application for patent, and to any patent issuing thereon, that contains or contained at
`any time- (A) a claim to a claimed invention that has an effective filing date as defined
`in section 1 OO(i) of title 35, United States Code, that is on or after the effective date
`described in this paragraph [i.e., March 16, 2013]; or (B) a specific reference under
`section 120, 121, 365(c) of title 35, United States Code, to any patent or application that
`contains or contained at any time such claim." (Commentary added for emphasis.)
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24,2013
`Page 6 of 11
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`and the copending parent CIP application contains a claim (claim 9) that finds support
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`under 35 U.S.C. § 112 only in Example 8, which was newly added to the parent
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`continuation-in-part application. Thus, claim 9 has an EFD after March 15, 2013.
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`For that reason, all of claims 10-18 should, for prior art purposes, be examined
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`solely through the lenses of AlA §§ 1 02(a)(1 ), (a)(2), and 103, as well as pre-AlA
`
`§ 1 02(g). That point is clearly explained by the USPTO:
`
`If an application (1) contains or contained at any time a
`claimed invention having an effective filing date that is before
`March 16, 2013, or ever claimed a right of priority or the
`benefit of an earlier filing date under 35 U.S.C. 119, 120,
`121, or 365 based upon an earlier application that ever
`contained a claimed invention having an effective filing date
`that is before March 16, 2013 [such as claims 10-18], and
`(2) also contains or contained at any time any claimed
`invention having an effective filing date that is on or after
`March 16, 2013, or ever claimed a right of priority or the
`benefit of an earlier filing date under 35 U.S.C. 119, 120,
`121, or 365 based upon an earlier application that ever
`contained a claimed invention having an effective filing date
`that is on or after March 16, 2013 [here that is claim 9 of
`the copending parent CIP], then AlA 35 U.S.C. 102 and
`103 apply to the application, and each claimed invention in
`the application is also subject to pre-AlA 35 U.S.C. 1 02(g).
`
`SEC. 3(n)(2): "The provisions of sections 1 02(g), 135, and 291 of title 35, United States
`Code, as in effect on the day before the effective date set forth in paragraph (1) of this
`subsection [March 15, 2013], shall apply to each claim of an application for patent, and
`any patent issued thereon, for which the amendments made by this section also apply,
`if such application or patent contains or contained at any time- (A) a claim to an
`invention having an effective filing date as defined in section 1 OO(i) of title 35, United
`States Code, that occurs before the effective date set forth in paragraph (1) of this
`subsection [March 16, 2013]; or (B) a specific reference under section 120, 121, or
`365(c) of title 35, United States Code, to any patent or application that contains or
`contained at any time such a claim." (Commentary added for emphasis.)
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 7 of 11
`
`See Examination Guidelines for Implementing the First Inventor to File Provisions of the
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`Leahy-Smith America Invents Act, 78 Fed. Reg. 11,059, 11,072 (February 14, 2013)
`
`(commentary and bold added for emphasis).
`
`Ill. Claims 10-18 Find Support in the '351 Application
`
`A. Claim 10
`
`Claim 10 is an independent claim, reciting "[a] pharmaceutical single-use, unit-
`
`dose formulation for intravenous administration to a human to reduce the likelihood of
`
`cancer chemotherapy-induced nausea and vomiting, comprising a 5 ml sterile aqueous
`
`isotonic solution buffered at a pH of 5.0 ± 0.5, said solution comprising: palonosetron
`
`hydrochloride in an amount of 0.25 mg based on the weight of its free base; optionally a
`
`chelating agent; and from 10 mg/ml to 80 mg/ml mannitol, wherein said formulation is
`
`stable at 24 months when stored at room temperature." Support for claim 10 can be
`
`found throughout the specification of the '351 Application, for instance at:
`
`- the abstract at page 21 ;
`
`- page 2, lines 3-6 and lines 24-29;
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`- page 3, lines 1-5, lines 11-20;
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`- page 3, lines 21 to page 4, line 13;
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`- page 4, lines 19-21;
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`-page 5, lines 5-15;
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`- page 5, line 26 to page 6, line 2;
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`- page 6, lines 16-20;
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`-page 6, line 21 to page 7, line 1;
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 8 of 11
`
`- page 7, lines 3-6;
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`- page 8, lines 2-5, lines 9-11, lines 13-25;
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`-page 9, lines 12-17, lines 21-23;
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`-page 10, lines 3-18; and
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`-original claims 1, 4, 5, 7, 8, 10, 12, 15, 18, 19, 21, 23, 25, 33, 36, 38, 39, 41, 43,
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`44, 46, 47, 50, 51, 54, 56, and 57.
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`Claim 1 0 recites "wherein said formulation is stable at 24 months when stored at
`
`room temperature." Support for this phrase can be found throughout the specification of
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`the '351 Application, for instance at page 3, lines 11-12, page 5, lines 5-7, and page 10,
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`lines 9-18. On July 25, 2003, furthermore, US FDA approved Helsinn's Aloxi®
`
`(palonosetron hydrochloride injection) product, which is within the scope of the claims,
`
`for a 2 year shelf life. See Exhibit A, FDA approval letter ("[B]ased on the primary
`
`stability data submitted, we are granting a 24-month expiration period for this product.").
`
`Hence, the written description and enablement of the new claims is tightly bound to the
`
`drug product approved by FDA and within the scope of the claims.
`
`B. Claim 11
`
`Claim 11 depends from claim 10, and recites "[t]he pharmaceutical formulation of
`
`claim 1 0, wherein said mannitol is in an amount of 41.5 mg/ml." Support for claim 11
`
`can be found throughout the specification of the '351 Application, such as the support
`
`for claim 10 as set forth above. Additional support may be found, for instance at:
`
`- page 9, lines 28 to page 10, line 2;
`
`- page 11, line 25 to page 12, line 2; and
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 9 of 11
`
`- page 12, Example 4.
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`C. Claims 12-15
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`Claim 12 depends from claim 10, and recites "[t]he pharmaceutical formulation of
`
`claim 10, wherein said solution further comprises a chelating agent." Claim 13 depends
`
`from claim 12, and recites "[t]he pharmaceutical formulation of claim 12, wherein said
`
`chelating agent is EDTA." Claim 14 depends from claim 13, and recites "[t]he
`
`pharmaceutical formulation of claim 13, wherein said EDTA is in an amount of from
`
`0.005 mg/ml to 1.0 mg/ml." Claim 15 depends from claim 14, and recites "[t]he
`
`pharmaceutical formulation of claim 14, wherein said EDTA is in an amount of 0.5
`
`mg/ml." Support for claims 12-15 can be found throughout the specification of the '351
`
`Application, such as the support for claim 10 as set forth above. Additional support may
`
`be found, for instance at:
`
`-page 9, lines 9-11, lines 17-21;
`
`- page 12, Example 4; and
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`- original claims 9, 20, 34, 35, and 52.
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`D. Claims 16-17
`
`Claim 16 depends from claim 10, and recites "[t]he pharmaceutical formulation of
`
`claim 10, wherein said solution further comprises a citrate buffer." Claim 17 depends
`
`from claim 16, and recites "[t]he pharmaceutical formulation of claim 16, wherein said
`
`citrate buffer is at a concentration of 20 millimolar." Support for claims 16-17 can be
`
`found throughout the specification of the '351 Application, such as the support for claim
`
`10 as set forth above. Additional support may be found, for instance at:
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`5582030v1
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`Exh. 1020
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`

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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 10 of 11
`
`- page 11, Example 2; and
`
`- pages 11-12, Example 3.
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`E. Claim 18
`
`Claim 18 is an independent claim, reciting "[a] pharmaceutical single-use, unit-
`
`dose formulation for intravenous administration to a human to reduce the likelihood of
`
`cancer chemotherapy-induced nausea and vomiting, comprising a 5 ml sterile aqueous
`
`isotonic solution buffered at a pH of 5.0 ± 0.5, said solution comprising: palonosetron
`
`hydrochloride in an amount of 0.25 mg based on the weight of its free base; optionally
`
`a chelating agent; and from 10 mg/ml to 80 mg/ml mannitol, wherein said formulation
`
`is stable at 18 months when stored at room temperature." Support for claim 18 can be
`
`found throughout the specification of the '351 Application such as the support for claim
`
`1 0 as set forth above. Additional support may be found, for instance, at:
`
`-page 5, lines 5-7.
`
`Furthermore, US FDA approved Helsinn's Aloxi® (palonosetron hydrochloride
`
`injection) product, which is within the scope of the claims, for a 2 year shelf life. See
`
`Exhibit A, FDA approval letter ("[B]ased on the primary stability data submitted, we are
`
`granting a 24-month expiration period for this product."). And of course, that which is
`
`stable at 24 months is also stable at 18 months. Hence, the written description and
`
`enablement of the new claims is tightly bound to the drug product approved by FDA and
`
`within the scope of the claims.
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`5582030v1
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`Exh. 1020
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`Continuation of U.S. Application No. 13/901,437
`Preliminary Amendment
`May 24, 2013
`Page 11 of 11
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`If there is any fee due in connection with the filing of this Preliminary
`
`Amendment, please charge the fee to Deposit Account No. 504667.
`
`Respectfully submitted,
`
`By:_C&=---_~.....::....._~ _._,4__: __ - __ _
`Clark G. Sullivan
`Reg. No. 36,942
`
`ARNALL GOLDEN GREGORY LLP
`( 404) 873-8500
`(404) 873-8501 (fax)
`Customer No.: 53449
`
`Attorney Docket No.: 23278.2.US.9
`
`Attachment:
`- Exhibit A, FDA approval letter for Aloxi®
`
`5582030v1
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`Exh. 1020
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`Exhibit AExhibit A
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`
`
`Exhibit A
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`Exh. 1020
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`

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`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`Rockville, MD 20857
`
`NDA 21-372
`
`Helsinn Healthcare S.A.
`c/o August Consulting
`Attention: Craig Lehmann, Pharm. D.
`515 Capital of Texas Highway, Suite 150
`Austin, TX 78746
`
`Dear Dr Lehmann:
`
`Please refer to your new drug application (NDA) dated September 26, 2002, received
`September 27, 2002, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`Aloxi™ (palonosetron hydrochloride injection).
`
`We acknowledge receipt of your submissions dated October 11 and November 21, 2002 and
`January 24, April9, April24, May 15, June 6, June 9, June 13, June 16, June 18, June 20, June 25,
`July 1, July 17, and July 22, 2003.
`
`This new drug application provides for the use of Aloxi™ (palonosetron hydrochloride injection) for:
`1)
`the prevention of acute nausea and vomiting associated with initial and repeat courses of
`moderately and highly emetogenic cancer chemotherapy, and
`the prevention of delayed nausea and vomiting associated with initial and repeat courses of
`moderately emetogenic cancer chemotherapy.
`
`2)
`
`We completed our review of this application, as amended. It is approved, effective on the date ofthis
`letter, for use as recommended in the agreed-upon labe1ing text
`
`Please note that, based on the primary stability data submitted, we are granting a 24-month expiration
`period for this product. When additional stability data are available, an extension of the expiration
`period may be requested by submission of a prior approval supplemental new drug application.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert)
`and submitted labeling (carton label submitted June 25, 2003 and immediate container label submitted
`July l, 2003). Marketing the product with FPL that is not identical to the approved labeling text may
`render the product misbranded and an unapproved new drug.
`
`Please submit an electronic version of the FPL according to the f,JUidance for industry titled Providing
`Regu!atmy Submissions in Electronic Format~ NDA. Alternatively, you may submit 20 paper copies
`of the FPL as soon as it is available but no more than 30 days after it is printed. Individually mount 15
`of the copies on heavy-weight paper or similar material. For administrative purposes, designate this
`submission"FPL for approved NDA 21-372." Approval of this submission by FDA is not required
`before the labeling is used.
`
`Exh. 1020
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`

`

`NDA 21-372
`Page 2
`
`FDA's Pediatric Rule [at 21 CFR 314.55/21 CFR 60 1.27] was challenged in court. On October 17,
`2002, the court ruled that FDA did not have the authority to issue the Pediatric Rule and has barred
`FDA from enforcing it. Although the government decided not to pursue an appeal in the courts, it will
`work with Congress in an effort to enact legislation requiring pharmaceutical manufacturers to conduct
`appropriate pediatric clinical trials. In addition, third party interveners have decided to appeal the
`court's decision striking down the rule. Therefore, we encourage you to submit a pediatric plan that
`describes development of your product in the pediatric population where it may be used. Please be
`aware that whether or not this pediatric plan and subsequent submission of pediatric data will be
`required depends upon passage oflegislation or the success of the third party appeal. In any event, we
`hope you will decide to submit a pediatric plan and conduct the appropriate pediatric studies to provide
`important information on the safe and effective use of this drug in the relevant pediatric populations.
`
`The pediatric exclusivity provisions ofFDAMA as reauthorized by the Best Pharmaceuticals for
`Children Act are not affected by the court's ruling. Pediatric studies conducted under the terms of
`section 505A of the Federal Food, Drug, and Cosmetic Act may result in additional marketing
`exclusivity for certain products. You should refer to the Guidance for Industry on QualifYing for
`Pediatric Exclusivity (available on our web site at www.fda.gov/cder/pediatric) for details. We
`acknowledge your June 26, 2003 "Proposed Pediatric Study Request" submitted under (b)(4)---------
`W e are reviewing your submission and will respond to your proposal in a separate letter. FDA
`generally does not consider studies submitted to an NDA before issuance of a Written Request as
`responsive to the Written Request. Applicants should obtain a Written Request before submitting
`pediatric studies to an NDA.
`
`In addition, submit three copies of the introductory promotional materials that you propose to use for
`this product. Submit all proposed materials in draft or mock-up form, not final print. Send one copy to
`this division and two copies of both the promotional materials and the package insert directly to:
`
`Division ofDrug Marketing, Advertising, and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20857
`
`Please submit one market package of the drug product when it is available.
`
`We have not completed validation of the regulatory methods. However, we expect your continued
`cooperation to resolve any problems that may be identified.
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81 ). In addition, we request that you initiate a 15-day report [21 CFR 314.80( c)] for
`each ofthe following:
`• All spontaneous reports of constipation requiring hospitalization or emergency room visit
`• All spontaneous reports of possible complications of constipation such as obstruction,
`perforation, intestinal ulceration, toxic megacolon, ileus, or impaction resulting in
`hospitalization or emergency room visit
`• All spontaneous reports of any cardiovascular adverse event
`
`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse event
`reports that are received directly by the FDA. New molecular entities and important new biologics
`
`Exh. 1020
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`NDA 21-372
`Page 3
`
`quality for inclusion for three years after approval. Your firm is eligible to receive copies of reports for
`this product. To participate in the program, please see the enrollment instructions and program
`description details at www. fda.gov/medwatch/report/mmp.htm.
`
`If you have any questions, call Brian Strongin, RPh., M.B.A, Regulatory Project Manager at (30 1)
`827-7473.
`
`Sincerely,
`
`Julie Beitz, M.D.
`Deputy Director
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
`
`Enclosure
`
`Exh. 1020
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/sf
`Julie Beitz
`7/25/03 08:45:03 AM
`
`Exh. 1020
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