Exhibit 1004
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`‘183 Patent File History (“FH183”)
`Amendment 4/5/2007
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`ITED STATES PATENT AND TRADEMARK OFFICE
`In re patent application of:
`Plachetka, et al.
`Appl. No.: 10/741,592
`Filed: December 22, 2003
`For: Multilayer Dosage Forms Containing
`NSAIDs and Triptans
`
`Art Unit: 1615
`Examiner: Sharon Kennedy
`Atty. Dkt.: 7569/80923
`
`Amendment and Response Under 37 C.F.R. §1.111
`Commissioner of Patents
`U.S. Patent and Trademark Office
`Customer Service Window, MS Amendment
`Randolph Building
`401 Dulany Street
`Alexandria, VA 22314
`Sir:
`
`In response to the Office Action dated December 20, 2006, Applicants respectfully
`request reconsideration of the above-captioned application in view of the following amendments
`and remarks.
`
`A Listing of Claims begins on page 2 of the present document.
`
`Remarks/ Arguments begin on page 5 of the present document.
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`2
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`Amendments to the Claims
`Please amend claims as shown below in the List of Claims.
`
`l.
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`2.
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`3.
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`4.
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`5.
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`6.
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`List of Claims
`(Currently) A multilayer pharmaceutical tablet comprising naproxen and a triptan and,
`wherein:
`a)
`substantially all of said triptan is in a first layer of said tablet and
`substantially all of said naproxen is in a second, separate layer; and
`said first layer and said second layer are in a side by side arrangement
`such that the dissolution of said
`naproxen occurs independently of
`said triptan.
`
`b)
`
`(Original) The tablet of claim I, wherein said naproxen is in the form of naproxen
`sodium at between 200 and 600 mg.
`
`(Original) The tablet of claim 1, wherein said triptan is selected from the group
`consisting of: sumatriptan, eletriptan, rizatriptan, frovatriptan, almotriptan, zolmitriptan,
`and naratriptan.
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`(Original) The tablet of claim 1, wherein said triptan is sumatriptan.
`
`(Original) The tablet of claim 4, wherein said sumatriptan is in the form of sumatriptan
`succinate at between 25 and I 00 mg.
`
`(Original) The tablet of claim 1, wherein said first layer and said second layer are
`juxtaposed symmetrically along a single planar surface such that essentially all of said
`first layer is on one side of said planar surface and essentially all of said second layer is
`on the other side of said planar surface.
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`10/741,592
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`7.
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`8.
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`9.
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`10.
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`11.
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`12.
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`13.
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`14.
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`15.
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`(Original) The tablet of claim 6, wherein said first layer and said second layer contact one
`another along said single planar surface.
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`(Original) The tablet of claim 6, wherein said first layer and said second layer are
`separated by at least one additional layer.
`
`(Original) The tablet of any one of claims 1-8, wherein said tablet is a bilayer dosage
`form.
`
`(Original) The tablet of any one of claims 1-8, further comprising a coating layer
`surrounding both said first layer and said second layer.
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`(Original) The tablet of any one of claims 2, 3 or 6-8, wherein said triptan is sumatriptan.
`
`(Original) The tablet of claim 11, wherein said sumatriptan is in the form of sumatriptan
`. succinate at between 25 and I 00 mg.
`
`comprising administering to said
`(Original) A method of treating a patient for
`patient the tablet of any one of claims 1-8, wherein said patient is treated at a dosage
`effective to alleviate the pain associated with said headache.
`
`(Original) The method of claim 13, wherein said headache is migraine headache.
`
`(Original) A method of treating a patient for headache, comprising administering to said
`patient the tablet of claim 9, wherein said patient is treated at a dosage effective to
`alleviate the pain associated with said headache.
`
`16.
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`(Original) The method of claim 15, wherein said headache is migraine headache.
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`17.
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`(Original) A method of treating a patient for headache, comprising administering to said
`patient the tablet of claim 10, wherein said patient is treated at a dosage effective to
`alleviate the pain associated with said headache.
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`18.
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`(Original) The method of claim 17, wherein said headache is migraine headache.
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`19.
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`20.
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`(Previously presented) A multilayer pharmaceutical tablet comprising an NSAID and a
`triptan, wherein
`a)
`substantially all of said triptan is in a first layer of said tablet and
`substantially all of said NSAID is in a second, separate layer; and
`said first layer and said second layer are in a side by side arrangement
`such that the dissolution of said NSAID occurs independently of said
`triptan.
`
`b)
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`(Previously presented) A method for rapid release of sumatriptan and naproxen from an
`oral dosage form in a patient, the method comprising administering to said patient the
`tablet of claim 4 or claim 5, wherein in said patient, dissolution of sumatriptan and
`naproxen is faster from said tablet as compared to dissolution of sumatriptan and
`naproxen from a tablet where sumatriptan and naproxen are in a physical admixture.
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`I.
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`Remarks
`Status of the Application and Claims
`As originally filed, the present application had a total of 18 claims. Claims 19 and 20
`were added in a Preliminary Amendment filed by Applicants on August 30, 2005. No further
`addition or cancellation of claims has taken place herein. ·
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`II.
`
`The Amendments
`Claim I was amended to correct a minor error pointed out by the Examiner. Specifically
`the term ''NSAID" in paragraph b) was changed to "naproxen." This amendment does not add
`new matter to the application and its entry is therefore respectfully requested.
`
`The Rejections
`Rejection of Claims Under 35USC§112, Second Paragraph
`I.
`On page 2 of the Office Action, the Examiner rejects claims 1-20 under 35 USC §112.
`second paragraph. It is alleged that the claim is indefinite because there is insufficient antecedent
`basis for the phrase "said NSAID" in paragraph b) of claim 1.
`
`In response, Applicants have amended paragraph b) in claim I so that it now refers to
`"said naproxen" rather than "said NSAID." In light of this amendment, Applicants respectfully
`submit that the Examiner's rejection has been overcome.
`
`Rejection of Claims Under 35 USC § 103
`II.
`On pages 2 and 3 of the Office Action, the Examiner rejects claims 1-20 under 35 USC
`§ 103 as being unpatentable over Plachetka (US 5,872, 145) in view ofSwintosky (US 2,951, 792).
`The Plachetka reference is cited as disclosing dosage forms containing naproxen and triptans and
`the reference by Swintosky is cited as demonstrating that the concept of separating tablet
`ingredients into different layers has long been known.
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`Applicants respectfully traverse this rejection.
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`Applicants do not dispute the Examiner's allegations that drug combinations utilizing
`triptans and naproxen were known in the prior art or that the concept of putting drugs in separate
`layers of dosage forms was well established. However, Applicants submit that the claims are
`directed to patentable "selection invention." In order to better understand the exact meaning of
`the terms that are used in the claims, reference should be made to the specification, and in
`particular, to page 3, lines 15-26, which read as follows:
`The layers [of the claimed dosage forms] should be arranged such that the
`individual therapeutic agents dissolve independently of one another, i.e.,
`dissolution should occur at approximately the same rate as would occur if the drugs
`were given separately. In this context, "approximately the same rate" indicates that
`the time for complete dissolution of agent when drugs are given in the combination
`tablet should require the same amount of time± 10% as when the same amount of
`agent is given alone. This can be achieved by placing the individual layers in a
`side-by-side arrangement, as opposed, for example, in a single layer tablet matrix
`containing both agents or one layer forming a core surrounded by the other layer. In
`a preferred embodiment, the layers are arranged so that they are juxtaposed
`symmetrically along a single planar surface such that essentially all of the triptan-
`containing layer is on one side of the plane and essentially all of the NSAID-
`containing layer is on the other side.
`The present claims require that naproxen and triptan be in a tablet in which they are
`segregated from one another in a "side by side arrangement" and in which their dissolution
`occurs independently of one another. The claims are limited to one very specific tablet
`architecture. Among the dosage forms falling outside the claims are: admixtures; any dosage
`fonns other than tablets; tablets in which one drug is in a core and surrounded by a layer or
`coating containing the second drug; and tablets containing multiple drug release pellets or
`microparticles. Applicants submit that there is nothing in the prior art that would lead one of skill
`to choose the claimed dosage form over many other possible choices. As such, the claims at least
`meet the novelty requirement for patentability.
`
`In order to meet the nonbviousness requirement, a selection invention cannot be simply
`an arbitrary choice. Thus, to be patentable, there must be some advantage in the specific dosage
`fonn that Applicants have claimed that sets it apart from other dosage fonns that could have been
`chosen. Such an advantage is, in fact, demonstrated in the Examples section of the application.
`Example 1 describes the making of a bilayer tablet that falls within the scope of the present
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`claims as well as two dosage forms that do not: a tablet in which sumatiptan is in a film coat
`surrounding naproxen and a tablet in which naproxen and sumatriptan are in admixture. The
`dissolution characteristics of these tablets are then compared in Example 2.
`
`The rate at which naproxen is released from the different tablets is shown in Table 6
`(page 14 of the application) and the rate at which sumatriptan is released is shown in Table 7
`(page 15 of the application). The results demonstrate that naproxen is released much more
`rapidly from the bilayer tablet (see results in Table 6 for the first 30 minutes). In addition,
`sumatriptan is also released more rapidly from the bilayer tablet, even when compared to the
`tablet in which sumatriptan is located in an outer coating (see Table 7). Since the claimed drug
`combinations would be used in treating patients for pain, especially pain associated with
`migraine headache, the rate at which drugs are released after ingestion by a patient is a very
`important consideration, and the claimed dosage forms are thus clearly superior to the other
`tested formulations. The advantages also extend to dissolution following storage (see Tables 8
`and 9), stability (see Table 10) and pharmacokinetic characteristics of the claimed dosage form,
`as described in Example 3.
`
`Applicants acknowledge that Swintowsky disclosed a bilayer dosage form similar to that
`which is claimed in the present invention, but note that Swintowsky was endeavoring to combine
`different formulations of a single drug in a single dosage form. Applicants are by contrast
`combining two separate drugs in a single dosage form, where both drugs are formulated for
`immediate release. Whyte discloses a bilayer dosage form in which two chemicals which are
`reactive with each other are arranged to have minimal contact with each other. Applicants are not
`attempting to prevent reaction of two chemical entities, but rather to provide for superior release
`characteristics. Thus, the particular references cited by the Examiner do not appear to Applicant
`to be directly relevant to the present invention.
`
`In light of the results discussed above, Applicants submit that the claimed tablet
`arrangement does not represent an arbitrary selection. It produces a tablet that has dramatically
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`improved dissolution characteristics compared to other dosage forms. Moreover, there is nothing
`in the prior art to suggest the existence this advantage.
`
`The Examiner seems to suggest that one of skill in the art who is developing a drug
`combination would try many different ways of delivering the drugs and many different dosage
`forms. However, the existence of an incentive to experiment with different dosage forms is
`irrelevant to the issue of obviousness. If one dosage form is found to be unexpectedly superior to
`others, it may be patentable regardless of how it is discovered. In this regard, it should be noted
`that 35 USC§ 103 expressly states: "Patentability shaIJ not be negatived by the manner in which
`the invention was made."
`
`Conclusion
`In light of the amendments and discussion above, Applicants respectfully submit that all
`of the Examiner's rejections have been overcome. It is therefore requested that these rejections be
`withdrawn and that the claims presently pending in the application be allowed.
`
`If, in the opinion of the Examiner, a phone call may help to expedite the prosecution of
`this application, the Examiner is invited to call Applicant's undersigned attorney at {240)864- ·
`0915.
`
`Respectfully submitted,
`LAW OFFICE OF MICHAEL A. SANZO
`
`Michael A. Sanzo
`Reg. No. 36,912
`Attorney for Applicants
`
`Date: If
`'4¥>7
`15400 c!lhoun Drive, Suite 125
`Rockville, Md. 20855
`{240)864-0915