ATTORNEY DOCKET NO. 23278.2.US.8
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`Giorgio CALDERARI et al.
`
`Application No.: Not Yet Assigned
`
`Continuation-in-Part of U.S. Application
`No. 13/087,012
`
`Filed: Herewith
`
`For: LIQUID PHARMACEUTICAL
`FORMULATIONS OF PALONOSETRON
`
`) Group Art Unit: Not Yet Assigned
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`)
`)
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`) Examiner: Not Yet Assigned
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`)
`)
`)
`) Confirmation No.: Not Yet Assigned
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`)
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
`
`IDENTIFICATION OF CONTINUATION-IN-PART CLAIM SUPPORT
`REQUIRED UNDER 37 C.F.R. § 1.78(d)(3) AND CHOICE OF LAW
`
`As required by 37 C.F.R. § 1.78(d)(3), as amended effective November 1, 2007,
`
`the undersigned representative of the applicant provides the following information.
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`I.
`
`Introduction
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`Claims 1-8 of the above-identified continuation-in-part application find support
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`under 35 U.S.C. § 112 in the provisional application, 60/444,351 ("the '351 Application")
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`filed January 30, 2003, of co pending Application No. 13/087,012 filed April 4, 2011 (see
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`Domestic Benefit/National Stage Information in the accompanying Application Data
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`Sheet, which e.stablishes a chain of copendency and specific reference from copending
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`Application No. 13/087,012 back to the '351 Application). Thus, claims 1-8 have an
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`effective filing date (EFD) prior to March 16, 2013.
`
`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 1016
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`Exh. 1016
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`

`
`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 2 of 8
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`Claim 9 finds support under 35 U.S.C. § 112 only in newly added Example 8 of
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`the continuation-in-part application filed herewith. Thus, claim 9 has an EFD after
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`March 15, 2013.
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`II. Choice of Law
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`Hence, this application falls under both transition provisions 3(n)(1) (because of
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`claim 9) and 3(n)(2) (because of claims 1-8) of the America Invents Act (AIA). 1 For that
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`reason, all of claims 1-9 should, for prior art purposes, be examined solely through the
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`lenses of AlA §§ 1 02(a)(1 ), (a)(2), and 103, as well as pre-AlA § 1 02(g). That point is
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`clearly explained by the USPTO:
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`[S]ection 3(n)(2) does indicate that the prov1s1ons of 35
`U.S.C. 1 02(g), 135, and 291 as in effect on March 15, 2013,
`shall apply to "each claim" of an application for patent, and
`not simply the claim or claims having an effective filing date
`
`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.)
`
`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.)
`
`2
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`Exh. 1016
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`

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`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 3 of 8
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`that occurs before March 16, 2013, if the condition specified
`in section 3(n)(2) occurs. Therefore, "each claim" of an
`application presenting a claim to a claimed invention that has
`an effective filing date before March 16, 2013 [here claims
`1-8], but also presenting claims to a claimed invention that
`has an effective filing date on or after March 16, 2013 [here
`claim 9], is subject to AlA 35 U.S.C. 102 and 103 and is also
`subject to the provisions of 35 U.S.C. 1 02(g), 135, and 291
`as in effect on March 15, 2013.
`
`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, 11,069 (February 14, 2013)
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`(commentary added for emphasis).
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`Ill. Claims 1-8 Find Support in and Have an EFD of the Pre-AlA '351 Application
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`A. Claim 1
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`Claim 1 recites "[a] pharmaceutical single-use, unit-dose
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`formulation
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`for
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`intravenous administration to a human to reduce the likelihood of cancer chemotherapy-
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`induced nausea and vomiting, comprising a 5 ml sterile aqueous isotonic solution, said
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`solution comprising: palonosetron hydrochloride in an amount of 0.25 mg based on the
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`weight of its free base; from 0.005 mg/ml to 1.0 mg/ml EDTA; and from 10 mg/ml to
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`80 mg/ml mannitol, wherein said formulation is stable at 24 months when stored at
`
`room temperature." Support for claim 1 can be found throughout the specification of
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`the '351 Application, for instance, at:
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`-the abstract at page 21;
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`- 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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`3
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`Exh. 1016
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`

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`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 4 of 8
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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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`-page 7, lines 3-6;
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`- page 8, lines 2-5, lines 9-11, and lines 13-15;
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`- page 9, lines 9-23;
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`- page 10, lines 3-18; and
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`-original claims 1, 4, 5, 8-10, 12, 33-36, 38, 39, 41, 44, 46, 47, 50-52, 54, and
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`57.
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`Claim 1 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®
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`(palonosetron hydrochloride injection) product, which is within the scope of the claims,
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`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.").
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`Hence, the written description and enablement of the new claims is tightly bound to the
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`drug product approved by FDA and within the scope of the claims.
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`4
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`Exh. 1016
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`

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`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 5 of 8
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`B. Claim 2
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`Claim 2 depends from claim 1, and recites "[t]he pharmaceutical formulation of
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`claim 1, wherein said EDTA is in an amount of 0.5 mg/ml." Support for claim 2 can be
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`found throughout the specification of the '351 Application, such as the support for claim
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`1 as set forth above. Additional support may be found, for instance, at:
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`-page 9, lines 9-11; and
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`- page 12, Example 4.
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`C. Claim 3
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`Claim 3 depends from claim 1, and recites "[t]he pharmaceutical formulation of
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`claim 1, wherein said mannitol is in an amount of 41.5 mg/ml." Support for claim 3 can
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`be found throughout the specification of the '351 Application, such as the support for
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`claim 1 as set forth above. Additional support may be found, for instance, at:
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`-page 9, lines 28 to page 10, line 2;
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`-page 11, line 25 to page 12, line 2; and
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`- page 12, Example 4.
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`D. Claims 4 and 5
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`Claim 4 depends from claim 1, and recites "[t]he pharmaceutical formulation of
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`claim 1, wherein said solution further comprises a citrate buffer." Claim 5 depends from
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`claim 4, and recites "[t]he pharmaceutical formulation of claim 4, wherein said citrate
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`buffer is at a concentration of 20 millimolar." Support for claims 4 and 5 can be found
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`throughout the specification of the '351 Application, such as the support for claim 1 as
`
`set forth above. Additional support may be found, for instance, at:
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`5
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`Exh. 1016
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`

`
`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 6 of 8
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`- page 11, Example 2; and
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`-pages 11-12, Example 3.
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`E. Claim 6
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`Claim 6 depends from claim 1, and recites "[t]he pharmaceutical formulation of
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`claim 1, wherein said solution is buffered at a pH of 5.0 ± 0.5." Support for claim 6 can
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`be found throughout the specification of the '351 Application, such as the support for
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`claim 1 as set forth above. Additional support may be found, for instance, at:
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`- page 8, lines 16-25;
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`- page 12, Example 4; and
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`-original claims 7, 15, 43, 56 and 69.
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`A. Claim 7
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`Claim 7 depends from claim 1 , and recites "[t]he pharmaceutical formulation of
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`claim 1, wherein said EDTA is in an amount of 0.5 mg/ml, wherein said mannitol is in
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`an amount of 41.5 mg/ml, wherein said solution further comprises a citrate buffer at a
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`concentration of 20 millimolar, and wherein said solution is buffered at a pH of 5.0 ±
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`0.5." Support for claim 7 can be found throughout the specification of the '351
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`Application, such as the support for claim 1 as set forth above. Additional support may
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`be found, for instance, at:
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`- page 11, Example 2; and
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`- page 12, Example 4.
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`6
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`Exh. 1016
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`

`
`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 7 of 8
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`B. Claim 8
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`Claim 8 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, said solution comprising: palonosetron hydrochloride in an amount of
`
`0.25 mg based on the weight of its free base; from 0.005 mg/ml to 1.0 mg/ml EDTA;
`
`and from 1 0 mg/ml to 80 mg/ml mannitol, wherein said formulation is stable at 18
`
`months when stored at room temperature." Support for claim 8 can be found
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`throughout the specification of the '351 Application, such as the support for claim 1 as
`
`set forth above. Additional support may be found, for instance, at:
`
`-page 5, lines 5-7.
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`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
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`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
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`stable at 24 months is also stable at 18 months. Hence, the written description and
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`enablement of the new claims is tightly bound to the drug product approved by FDA and
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`within the scope of the claims.
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`IV. Claim 9 Finds Support Only in the Instant Application and
`Thus, Has an AlA EFD
`
`Claim 9 is an independent claim, reciting "[a] pharmaceutical single-use, unit-
`
`dose formulation for intravenous administration to a human to reduce the likelihood of
`
`7
`
`Exh. 1016
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`

`
`Continuation-in-part of U.S. Application No. 13/087,012
`Identification of Claim Support
`May 23, 2013
`Page 8 of 8
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`cancer chemotherapy-induced nausea and vomiting, comprising a 50 mL sterile isotonic
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`solution buffered at a pH of 4.8 ± 0.5 comprising: palonosetron hydrochloride in an
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`amount of 0.75 mg based on the weight of its free base; 450.0 mg sodium chloride;
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`EDTA; 18.5 mg sodium citrate; and 7.8 mg citric acid monohydrate, wherein said
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`formulation is contained in an infusion bag." Support for claim 9 is found in Example 8
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`of the continuation-in-part application filed herewith.
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`If any fees are required for entry of this paper, please charge them to Deposit
`
`Account No. 504667.
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`Respectfully submitted,
`
`By: ~vj-~~
`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.8
`
`8
`
`Exh. 1016
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`

`
`Exhibit A
`
`Exhibit A
`
`Exh. 1016
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`

`
`~SiR VICEs
`
`.,"'"~'
`{JJE
`f-""•
`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 787 46
`
`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, April 9, 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:
`l) 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 of this
`letter, for use as recommended in the agreed-upon labeling 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 1, 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 &ruidance for industry titled Providing
`Regulatory Submissions in Electronic fonnat- 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. 1016
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`

`
`NDA 21-372
`Page 2
`
`FDA's Pediatric Rule [at 21 CFR 314.55/21 CFR 601.27] 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 of legislation 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 of Drug 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. 1016
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`

`
`NDA 21-372
`Page 3
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`qualify for inclusion for three years after approval. Your firm is eligible to receive copies of reports for
`this product. To participate in the prot:,rram, please see the enrollment instructions and program
`description details at www. fda.gov/medwatch/report/mmp.htm.
`
`Ifyou have any questions, call Brian Strongin, R.Ph., M.B.A, Regulatory Project Manager at (301)
`827-7473.
`
`Sincerely,
`
`Julie Beitz, M.D.
`Deputy Director
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
`
`Enclosure
`
`Exh. 1016
`
`

`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/s/
`
`Julie Beitz
`7/25/03 08:45:03 AM
`
`Exh. 1016