Filed VIA EFS-Web
`April21, 2014
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant(s): Wayne R. GOMBOTZ et al.
`
`Confirmation No.:
`
`6715
`
`Serial No.:
`
`13/401,496
`
`Group Art Unit No.: 1644
`
`Filed:
`
`Title:
`
`February 21, 2012
`
`Examiner: OUSPENSKI, ILIA I
`
`POLYPEPTIDE FORMULATION
`
`Docket No.:
`
`3382-US-CNT2
`
`RESPONSE TO OFFICE ACTION
`
`Mail Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`This paper is filed in response to the Office Action dated October 21, 2013.
`
`• Amendments to the Claims begin on page 2 of this paper.
`
`• Remarks begin on page 5 of this paper.
`
`Also requested herewith is a Petition for Extension of Time to reply for three (3)
`
`month, accompanied by authorization to charge the appropriate fees, and an Information
`
`Disclosure Statement.
`
`The Director is hereby authorized to charge any additional fees which may be
`
`required by the accompanying papers, or credit any overpayment to Deposit Account No. 09-
`
`0089.
`
`CERTIFICATE OF EFS-Web TRANSMISSION
`I hereby certify that this paper (along with any referred to as being attached or enclosed) is being transmitted to the
`United States Patent and Trademark Office via EFS-Web on the date indicated below:
`
`/Jae Cho/
`Jae Cho
`
`A ril21, 2014
`Date
`
`Ex. 2014-0001
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Amendments to the Claims
`
`Immunex Corporation
`3382-US-CNT2
`
`The listing of claims will replace all prior versions, and listings, of claims in the
`
`application:
`
`Claims 1 to 20 are cancelled.
`
`21. (Currently amended) A kit comprising a composition comprising a polypeptide that is an
`
`extracellular ligand-binding portion of a human p75 tumor necrosis factor receptor fused to
`
`the Fe region of a human IgG 1 and from about 10 mM to about 200 mM L-arginine, and
`
`instructions for use of said composition.
`
`22. (Currently amended) The kit of claim 23, wherein the composition is in a liquid state.
`
`23. (Currently amended) The kit of claim 22, wherein the composition is stefe6 in a pre(cid:173)
`
`filled sterile syringe.
`
`Claim 24 is cancelled.
`
`25. (Previously Presented) The kit of claim 21, further comprising a buffer.
`
`26. (Previously Presented) The kit of claim 25, wherein the buffer is selected from the group
`
`consisting of sodium phosphate, histidine, potassium phosphate, sodium or potassium citrate,
`
`maleic acid, ammonium acetate, tris-(hydroxymethyl)-aminomethane (tris), acetate and
`
`diethanolamine.
`
`Claim 27 is cancelled.
`
`28. (Previously Presented) The kit of claim 21, further comprising a tonicity modifier.
`
`29. (Previously Presented) The kit of claim 28, wherein the tonicity modifier is selected
`
`from the group consisting of arginine, cysteine, histidine, glycine, sodium chloride, potassium
`
`chloride, sodium citrate, sucrose, glucose and Mannitol.
`
`2
`
`Ex. 2014-0002
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Immunex Corporation
`3382-US-CNT2
`
`30. (Previously Presented) The kit of claim 29, wherein the tonicity modifier is sodium
`
`chloride.
`
`31. (Previously Presented) The kit of claim 21, further comprising an excipient.
`
`32. (Previously Presented) The kit of claim 29, further comprising an excipient.
`
`33. (Previously Presented) The kit of claim 31, wherein the excipient is selected from the
`
`group consisting of sucrose, lactose, glycerol, xylitol, sorbitol, Mannitol, maltose, inositol,
`
`trehalose, glucose, bovine serum albumin (BSA), human SA or recombinant HA, dextran,
`
`PV A, hydroxypropyl methylcellulose (HPMC), polyethyleneimine, gelatin,
`
`polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), polyethylene glycol, ethylene
`
`glycol, glycerol, dimethysulfoxide (DMSO), dimethylformamide (DMF), proline, L-serine,
`
`sodium glutamic acid, alanine, glycine, lysine hydrochloride, sarcosine, gamma-aminobutyric
`
`acid, polysorbate-20, polysorbate-SO, SDS, polysorbate, polyoxyethylene copolymer,
`
`potassium phosphate, sodium acetate, ammonium sulfate, magnesium sulfate, sodium sulfate,
`
`trimethylamine N-oxide, betaine, zinc ions, copper ions, calcium ions, manganese ions,
`
`magnesium ions, CHAPS, sucrose monolaurate, and 2-0-beta-mannoglycerate.
`
`34. (Previously Presented) The kit of claim 33, wherein the excipient is sucrose.
`
`35. (Currently amended) A kit comprising a stable pharmaceutical composition of about 10
`
`mg/ml to about 100 mg/ml of a polypeptide that is an extracellular ligand-binding portion of
`
`a human p75 tumor necrosis factor receptor fused to the Fe region of a human IgG 1, arul
`
`about 10 mM to about 200 mM L-arginine, and sodium phosphate, sodium chloride and
`
`sucrose.
`
`36. (Previously Presented) The kit of claim 35, wherein L-arginine is about 10 mM to about
`
`75mM.
`
`37. (Previously Presented) The kit of claim 35, wherein sodium phosphate is about 5 mM to
`
`about 100 mM.
`
`3
`
`Ex. 2014-0003
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Claim 3 8 is cancelled.
`
`Immunex Corporation
`3382-US-CNT2
`
`39. (Previously Presented) The kit of claim 35, wherein sucrose is about 0.5% to about
`
`1.5%.
`
`40. (Previously Presented) The kit of claim 35, wherein pH is about 5.5 to about 7.8.
`
`41. (Previously Presented) The kit of claim 35, having about 50 mg/ml ofthe polypeptide
`
`that is an extracellular ligand-binding portion of a human p75 tumor necrosis factor receptor
`
`fused to the Fe region of a human IgG 1, about 25 mM L-arginine, about 25 mM sodium
`
`phosphate, about 98 mM sodium chloride, about 1% sucrose, and wherein the composition is
`
`about pH 6.2.
`
`42. (New) The kit of claim 21, wherein the polypeptide is etanercept.
`
`43. (New) The kit of claim 25, wherein the polypeptide is etanercept.
`
`44. (New) The kit of claim 28, wherein the polypeptide is etanercept.
`
`45. (New) The kit of claim 31, wherein the polypeptide is etanercept.
`
`46. (New) The kit of claim 35, wherein the polypeptide is etanercept.
`
`4
`
`Ex. 2014-0004
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Amendments
`
`REMARKS
`
`Immunex Corporation
`3382-US-CNT2
`
`Claims 21, 22, 23, and 35 have been amended, claims 27 and 38 have been cancelled without
`
`prejudice or disclaimer, and new claims 42-46 are presented. Applicants reserve the right to
`
`pursue cancelled or amended subject matter in one or more timely filed related applications.
`
`Support for the amendments to claims 21 and 35 can be found at page 9, line 28 of the
`
`specification as filed. The amendment to claim 22 is merely clarifying, and fully supported
`
`at, for example, p.13, line 5 of the specification. The amendment to claim 23 is also to clarify
`
`the language. New claims 42-46 are supported in the specification at, for example, page 5,
`
`line 1. No new matter has been added by way of these amendments.
`
`Rejection
`
`35 U.S.C. § 103(a)
`
`Claims 21-23, 25, 26, 28-35 and 37-40 are rejected under 35 U.S.C. § 103(a) as allegedly
`
`being obvious over Kakuta et al. (US Patent Application No. 2003/0190316), as evidenced by
`
`Moreland et al. (Ann. Intern. Med. 1999; 130:478-486). The Office Action asserts that
`
`Kakuta et al. teach that pharmaceutical compositions containing antibodies are stabilized in
`
`formulations with L-arginine (citing paragraphs [0084] and [0085]), and that it would have
`
`been obvious to a person of ordinary skill in the art to substitute the p75 TNF receptor Fe
`
`fusion protein, whose Fe region is derived from an antibody, for antibodies in the
`
`formulations of Kakuta et al. Page 3 of the Office Action. Further, the Office Action states
`
`that one of ordinary skill in the art would have had a reasonable expectation of success
`
`because of the similarity between etanercept and an antibody, and in view of the teachings of
`
`Kakuta that high stable concentrations of protein can be achieved in the presence of L(cid:173)
`
`arginine, and further in view of the high skill in the art of making liquid pharmaceutical
`
`preparations of high molecular weight proteins. However, the Office Action indicated that
`
`Claims 27, 36 and 41 are objected to as being dependent upon a rejected base claim, but
`
`would be allowable if rewritten in independent form including the relevant limitations of the
`
`base and intervening claims.
`
`Applicants gratefully acknowledge the Examiner's indication of allowable subject matter in
`
`claims 27, 36, and 41, and respectfully traverse the rejection of the remaining claims. At the
`
`outset, Applicants submit that Kakuta et al. does not teach at the cited paragraphs that
`
`5
`
`Ex. 2014-0005
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Immunex Corporation
`3382-US-CNT2
`
`pharmaceutical compositions containing antibodies can be stabilized with L-arginine.
`
`Instead, Kakuta et al. teach at paragraphs [0084] and [0085] that a basic amino acid such as
`
`L-arginine can be ''used for adjusting the pH" (Kakuta at paragraph 84).
`
`Even assuming that Kakuta et al. did suggest that L-arginine could stabilize an antibody
`
`composition (which it does not), that would still not lead one of skill to expect it would
`
`stabilize a fusion protein which contains a completely different structure with a large non(cid:173)
`
`antibody component. In other words, the teaching relating to one protein cannot simply be
`
`transferred to another protein. As can be taken from Wang et al., 1999, Int. J. Pharmaceutics,
`
`185(2):129-188 (ofrecord, cited as D15 on the IDS)
`
`"there is no single pathway to follow in the selection of a suitable
`
`stabiliser(s)" (emphasis added, Wang et al., page 178, left column, last
`
`paragraph, lines 1-10).
`
`Moreover, according to the post-published document Daugherty et al, 2006, Advanced Drug
`
`Delivery Reviews, 58, pp. 686-706 (included on the Information Disclosure Statement filed
`
`with this response), a rather wide spectrum of agents can reduce protein aggregation rates and
`
`"[s]tudies have shown that different proteins benefit from different types
`
`o[anti-aggregating [actors, consistent with the notion that the interfacial
`
`surfaces that drive interactions leading to aggregation are protein
`
`specific" (emphasis added, page 693, paragraph bridging the columns).
`
`Further,
`
`" ... the interfacial surface of each antibody drug is unique and thus
`
`requires specific fOrmulations components to provide maximal stability
`
`and retention of activity" (emphasis added, Dauherty et al., page 690,
`
`right column, first paragraph, last sentence)
`
`Hence, even very similar antibodies may differ in aggregation behaviour (Dauherty et al.,
`
`page 693, left column, penultimate paragraph, last sentence) and stability requirements,
`
`which is due to the differences in surface-exposed amino acids that mediate antigen
`
`specificity (Dauherty et al., page 690, right column, first paragraph, penultimate sentence).
`
`6
`
`Ex. 2014-0006
`
`

`
`USSN 13/401,496
`Response to Office Action
`April21, 2014
`
`Immunex Corporation
`3382-US-CNT2
`
`Nevertheless, in order to advance prosecution, the limitation of claim 27 has been written into
`
`claim 21 and 35, and claim 27 has been cancelled. As the Office Action indicated claim 27
`
`would be allowable if rewritten in independent form, Applicant submits that this amendment
`
`renders the outstanding obviousness rejection moot. Applicants respectfully request
`
`withdrawal.
`
`CONCLUSION
`
`Applicants submit that the pending claims are patentable, and a favorable action is
`
`requested. Should the Examiner believe that any issues could be resolved by way of a
`
`teleconference, the Examiner is invited to telephone the undersigned representative of the
`
`Applicants, to discuss resolution thereof.
`
`Please send all future correspondence to:
`
`Respectfully submitted,
`
`CUSTOMER NO: 22932
`Immunex Corporation
`Law Department
`1201 Amgen Court West
`Seattle, WA 98119-3105
`
`/Kathleen Fowler/
`
`Kathleen Fowler
`Attorney/Agent for Applicant(s)
`Registration No.: 40,611
`Phone: (206) 265-784 7
`Date: April21, 2014
`
`7
`
`Ex. 2014-0007