301731 v1 

 

Allyn Z. Lite 

 alite@litedepalma.com

January 20, 2012 

VIA ECF

Honorable Tonianne J. Bongiovanni, U.S.M.J. 

United States District Court 

Clarkson S. Fisher Building & U.S. Courthouse 

402 East State Street 

Room 6052 

Trenton, NJ 08608 

Re: AstraZeneca vs. Hanmi, Civil Action No.: 11-760 (JAP) (TJB)

Dear Judge Bongiovanni: 

 This firm, along with Sughrue Mion, PLLC, represents the Hanmi Defendants in the 

above-referenced matter. We write in response to AstraZeneca's January 13, 2012 letter to the 

Court (D.I. 184) (requesting that certain portions of Hanmi's responsive Markman submissions 

be stricken) and the Court's instructions of January 17, 2012, directing this response. 

 Hanmi's responsive Markman submissions filed January 6, 2012 (D.I. 174, 175), were 

prepared in strict compliance with the Local Patent Rules, which govern the scope and content of 

the parties' Markman submissions. Local Patent Rule 4.5(c) provides that the parties 

"contemporaneously file and serve responding Markman briefs and any evidence supporting 

claim construction, including any responding experts’ certifications or declarations" within 60 

days of opening Markman submissions. As set forth below, Hanmi's responsive submissions 

contained a Declaration and certain exhibits provided solely as rebuttal to new and expanded 

theories of claim construction provided by AstraZeneca -- long after the time for its required 

disclosure had passed (i.e. in the Joint Claim Construction Statement. (D.I. 92, 92-1 ("Joint 

Statement")). Hanmi could not have disclosed in the Joint Statement (filed September 14, 2011) 

evidence it did not know it would need as rebuttal until November 7, 2011 or December 7, 2011, 

the dates of AstraZeneca's Opening Brief (D.I. 133) and Dr. Davies' deposition. For this reason, 

Hanmi respectfully requests that AstraZeneca's motion be denied, as well as its request for relief 

in the alternative. 

 The Local Patent Rules clearly contemplate the submission of responsive declarations 

and supporting evidence with responsive Markman briefs, but nowhere do they contemplate a 

third round of Markman briefing, or a second round of depositions. Hanmi should not be 

prejudiced by the delay incurred by (1) AstraZeneca's initial failure to comply with Local Patent 

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Rule 4.3(b), and (2) its belated request to delay the Markman schedule pending its taking 

additional discovery and submitting an additional Declaration, which are not provided for by the 

Rules and which AstraZeneca chose not to timely submit. 

Background

 Presently, AstraZeneca seeks to have stricken exhibits 3-5, 7 and 8–13 of Hanmi's 

responsive Markman submissions, as well as the selected portions of the Supplemental Atwood 

Declaration (D.I. 184-1 (Ex. B)) and Hanmi's responsive brief (D.I. 184-1 (Ex. C)) designated 

by AstraZeneca. All of these exhibits and the statements citing to them in Hanmi's responsive 

brief and supporting declaration relate to the terms "alkaline salt" in the '504 patent and 

"pharmaceutically acceptable salt" in the '192 patent. 

Argument

 AstraZeneca Disclosed New Alkaline Salts For The First Time In Its Brief And 

 Expert Testimony

 Local Patent Rule 4.3(b) requires as part of the parties' Joint Statement identification of: 

• all references from the intrinsic evidence that support that construction 

• any extrinsic evidence known to the party on which it intends to rely 

either to support its proposed construction or to oppose any other party's 

proposed construction. L. Pat. R. 4.3(b) (emphasis added). 

 Because only extrinsic evidence known to the party at the time of the Joint Statement 

must be disclosed, the Rules clearly allow for the submission of rebuttal extrinsic evidence, e.g., 

evidence not known or foreseen at the time of filing of the Joint Statement. In the Joint 

Statement, AstraZeneca identified seven extrinsic references supporting its proposed 

constructions of "alkaline salt" and "pharmaceutically acceptable salt." The '974 and EP 495 

patents disclose the same six salt species as the '504 patent, plus the titanium salt and 

guanidinium salt; the three Marie references disclose the strontium salt; the Chambers Dictionary 

disclosed no salts; and the Berge reference was cited as "listing over twenty cations known to be 

used in salts fit for human consumption." (D.I. 92-1, p. 2). Substantively, the Berge reference 

lists 21 cations potentially useful in salt formation, 9 of which are metals and 12 of which are 

organic. (D.I. 112-4) (Many of the metal cations are the same as those listed in the '504 patent 

(Ca2+, Li+

, Mg2+, K+, Na+), while others are not.) Thus, as of the filing of the Joint Claim 

Construction and Prehearing Statement, Hanmi understood that AstraZeneca's "any basic salt" 

proposed construction would be supported by intrinsic and extrinsic evidence showing -- at most

-- 20 or so salt species not disclosed in the '504 patent. 

 AstraZeneca's opening Markman brief (D.I. 133) went further, and broadened the types 

of salt species within the proposed scope of the claims to include "at least, the alkaline metals 

and alkaline earth metals," as well as "an ammonium group, which is an honorary alkaline salt." 

(D.I. 133, p. 12). In his supporting declaration, Dr. Davies stated that persons of ordinary skill 

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would understand that suitable cations for alkaline salt include "at least, cations of all of the 

metals in Groups I and II (lithium, sodium, potassium, rubidium, caesium, beryllium, 

magnesium, calcium, strontium or barium) as well as ammonium." (D.I. 133-3, ¶¶ 36-37 

(emphasis added)). Nowhere prior to its opening Markman brief or Declaration in support did 

AstraZeneca disclose that all Group I and Group II elements, particularly rubidium, caesium, 

beryllium, barium (and honorary ammonium) were included within its proposed construction of 

"alkaline salt." 

 At his deposition, Dr. Davies went still further, stating that "the '504 patent covers all

alkaline salts". . . ; "All alkaline salts fulfill the criteria covered by the patent" (D.I. 175-1 

Davies Tr., p. 172); "Well, in principle, all of the metals could form salts. And there are a lot 

of metals." (p. 160). Dr. Davies also explained that a number of organic salts would be within 

the scope of the proposed definition as well. (D.I. 175-1, Davies Tr. at 154-157 (formation of 

tetraalkyl ammonium salts); 158-159 (formation of pentamethyl guanidine, guanidinium salts)) 

and Exhibit 1, Davies Tr. at 241-242 (formation of some organic salts)). At no time prior to Dr. 

Davies' deposition did AstraZeneca disclose that all metals would be within the scope of 

AstraZeneca's proposed construction. The evidence referred to in the Joint Statement referred to 

-- at most-- the 5 metal species listed in the '504 patent, titanium, strontium, and 3 or 4 additional 

metals from the Berge reference. 

 Confronted with Astra Zeneca's clear decision to expand the scope of "alkaline salt" 

beyond what the originally cited extrinsic evidence supported, Hanmi was left with no choice but 

to present a focused response to several of the Group I and Group II salts about which it was 

never provided notice. At least Exhibits 3-5 and 7, ¶¶ 14 – 21 of the Supp. Atwood Decl. and pp. 

3-4 of Hanmi's responsive brief address AstraZeneca's reliance on previously undisclosed 

beryllium, cesium, francium, radium, rubidium, and barium.1

AstraZeneca Also Put Forward A New Theory Not Previously Disclosed

AstraZeneca also urges that the correct construction of “alkaline” salt includes a 

limitation that they be "suitable for use in a pharmaceutical formulation." The extrinsic evidence 

AstraZeneca disclosed is referred to above. The three Marie articles relied on by AstraZeneca 

refer to the administration of various strontium compounds to laboratory mice and rats and say 

nothing about whether any of the compounds disclosed are suitable for use in a pharmaceutical 

formulation. Of the 21 cations in the Berge article disclosed as potentially useful, one third of 

them had not been approved in the U.S. and were only reported based on their use in other 

 

1

 Dr. Davies testified at his deposition that, e.g., thallium (a transition metal) would not be 

included within his definition of “alkaline salt” because it was toxic. (Ex. 1, Davies Tr. at 83, 

173.) It would be a strange and manifestly unfair result if Dr. Davies could unilaterally reshape 

the contours of “alkaline salt” by discarding toxic thallium salts from AstraZeneca’s proposed 

definition, but Hanmi were not permitted to challenge those moving contours based on the 

toxicity of certain salt species on rebuttal, the first opportunity it had to do so. Hanmi's 

responsive submission highlights the toxicity of certain Group I and Group II salts, which is no 

more than Dr. Davies did at his deposition. 

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countries. (D.I. 112-4). Moreover, the Berge reference contained no disclosure of how to 

determine whether or not a salt was “suitable for use in pharmaceutical formulations,” and 

specifically described toxicities associated with calcium, lithium, sodium, etc. salts. (D.I. 112-4, 

page 15 of Berge). None of the other references describe how to determine whether or not a 

particular salt was pharmaceutically acceptable. 

 Undaunted by the lack of clear guidance in the extrinsic evidence it cited, AstraZeneca 

posited for the first time in its opening Markman brief that since the claims were drawn to a 

'pharmaceutical formulation' comprising an "alkaline salt," the term "pharmaceutical 

formulation" would be understood to limit "alkaline salts" to those salts suitable for use in a 

pharmaceutical formulation." (D.I. 133, p. 8.) Dr. Davies confirmed at his deposition that the 

“pharmaceutical acceptability” requirement was context-driven, based on the claims and the 

patent specification. (Ex. 1, Davies Tr., pp. 70-73.) As best understood, Dr. Davies’ position is 

that “if an alkaline salt exists in a pharmaceutical formulation as claimed, the salt must itself be 

pharmaceutically acceptable.” This theory was never disclosed in the Joint Statement and is 

most certainly not supported by any of the evidence AstraZeneca cited. At best, AstraZeneca’s 

evidence can fairly be read to say that any potential salt would have to be studied to determine its 

suitability for use in a pharmaceutical formulation. 

 Faced with this new theory, Prof. Atwood provided an example of alkaline earth salts of a 

drug in a pharmaceutical formulation that were not by themselves pharmaceutically acceptable 

because of their high pH values in solution, but were formulated to be acceptable in a 

pharmaceutical preparation. As such, ¶ 40 of Prof. Atwood's Declaration is proper rebuttal to 

evidence newly raised by AstraZeneca and Dr. Davies well after the filing of the Joint Statement. 

AstraZeneca Relied On New Evidence In Support Of "Pharmaceutically Acceptable

 Salt"

 Finally, AstraZeneca proposed a construction of "pharmaceutically acceptable salt" that is 

the same as its proposed construction for "alkaline salt" in the Joint Statement (e.g., "a basic salt. 

.."), and cited as part of its intrinsic evidence several portions of the '504 patent in support: Col. 

2, l. 42 - Col. 3, l. 55; Col. 4, l. 51 -Col. 5 l. 1; Examples 1–7; claims 1–7, 10. (D.I. 92-1, p. 2). 

In its opening Markman brief, AstraZeneca stated that "the meaning of 'pharmaceutically 

acceptable salt' in the ’192 patent claims is the same as that for 'alkaline salt in the '504 patent 

claims" (D.I. 133, p. 21), but went further, arguing that: 

• in the context of the '504 patent, the ordinary meaning of “alkaline salt” is 

a salt of esomeprazole that is generated under basic or alkaline 

conditions (D.I. 133 p. 12). 

• alkaline salts were surprisingly stable under alkaline conditions, "as 

contrasted to the acidic conditions employed in prior art in unsuccessful 

efforts to prepare 'optically pure [individual enantiomers of] 

omeprazole.'" (D.I. 133, p. 22). 

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 In support of its argument, AstraZeneca cited Col. 13, l. 31 -- Col. 14, l. 4 -- Col. 1, ll. 

27–42 of the '504 patent, which specifically described the prior art preparation of omeprazole 

under acidic conditions in the DE 455 patent ("the Kohl reference"). But that portion of the '504 

patent was never disclosed by AstraZeneca in the Joint Statement as intrinsic evidence upon 

which it intended to rely. (D.I. 92-1, p. 2 ("alkaline salt" in the '504 patent) and p. 25 

("pharmaceutically acceptable salt" in the '192 patent)). AstraZeneca first raised the '504 patent 

discussion of the Kohl reference in its opening brief to support its argument that acidic 

conditions could not be used to prepare omeprazole. Dr. Davies augmented the arguments made 

in AstraZeneca's opening brief, stating that there was no evidence that the authors of the Kohl 

reference were able to obtain optically pure enantiomers of omeprazole at all. (Ex. 1. Davies Tr., 

pp. 145-146). Prof. Atwood's statements in ¶¶ 50-51 of his Supplemental Declaration provide a 

focused response to AstraZeneca's newly minted but factually incorrect statement that the prior 

art did not show how to produce optically pure enantiomers of omeprazole under acidic 

conditions. Because Hanmi had no advance notice of this new argument or of the intrinsic 

evidence AstraZeneca would rely on in support of it, Hanmi could not have disclosed its 

opposing evidence in the Joint Statement, and therefore Prof. Atwood's comments constituted 

proper rebuttal. 

 All Of AstraZeneca's Arguments And Positions Concerning Acid Salts Were Raised 

 For The First Time In Its Opening Submissions

 AstraZeneca's opening submissions suggested for the first time ever that acid salts of 

esomeprazole could not be formed, despite the '192 patent's express definition of 

"pharmaceutically acceptable salt" at D.I. 111-9 at column 4, lines 13-16 (both acid and alkaline 

pharmaceutically acceptable salts).2 See D.I. 133, pp. 9, 17-18. No paper in this case, including 

the Joint Statement, ever contained arguments or evidence purporting to claim that acid salts 

could not be formed, would not be stable, or were inoperative. Therefore, Hanmi was fully 

justified in establishing that acid salts of esomeprazole could easily be formed, based in part on 

AstraZeneca's own prior art patents describing acid salts of, e.g., omeprazole. AstraZeneca's 

arguments that any acid salt rebuttal is improper are specious. 

 Paragraphs 53-56 of the Supplemental Atwood Declaration and the single sentence in 

Hanmi's responsive brief summarizing those paragraphs (D.I. 174, p. 17) refer to literature 

examples disclosing acid salts of omeprazole. One reference in particular is AstraZeneca's own 

prior art '257 patent, which lists a number of possible acid salts of, e.g., omeprazole. As such, 

each of these portions of Hanmi's responsive submissions are proper rebuttal to statements and 

theories raised for the first time by AstraZeneca after the filing of the Joint Statement. 

 

2

 In contrast, Dr. Davies' Declaration stated that "(–)-omeprazole is ‘amphoteric,’ which means 

that it is able to form a salt either under basic conditions by loss of a proton or under acidic 

conditions by addition of a proton." (D.I. 133-3, Davies Decl., ¶¶ 38-40 at pp. 11-12.) Dr. 

Davies even provided an illustration of how an acid salt of (-)-omeprazole could be formed. Id. 

at ¶ 40. At his deposition, however, Dr. Davies testified that he was not aware of the preparation 

of any acid salts of either (-)-omeprazole or omeprazole, and that he would not expect them to be 

stable. (Ex. 1, Davies Tr., pp. 125-127.) 

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 Because all of the references and portions of Hanmi's responsive Markman submissions 

that AstraZeneca now seeks to strike were based on new evidence (intrinsic or extrinsic) never 

disclosed in the Joint Statement, Hanmi could not have disclosed its responsive evidence at the 

time of filing of the Joint Statement. Hanmi's responsive submission complied with Local Pat. 

Rule 4.3(c) and constituted proper rebuttal; as a result, AstraZeneca's motion should be denied.3

Given Hanmi's showing that its responsive submissions were entirely proper rebuttal to 

new evidence, arguments, positions and theories raised for the first time in AstraZeneca's 

opening submissions, it is clear that the present tactic is simply one of attempted delay. The 

record is clear that AstraZeneca never previously mentioned all Group I and Group II metals as 

suitable cations; Hanmi had every right to establish the toxicity and inoperability of some of 

them as rebuttal. AstraZeneca never argued the inoperability of acid salts of esomeprazole until 

its opening submissions; Hanmi again had every right to establish in rebuttal that AstraZeneca 

was plainly wrong based on AstraZeneca's own prior art patents. The same is true for the other 

new evidence, positions and theories raised for the first time in AstraZeneca's opening 

submissions. 

 AstraZeneca knows well that delaying the Markman hearing could well delay the 

ultimate resolution of this case because the balance of the case schedule remains to be set 

following the Court's Markman rulings. Judicial economy and principles of fundamental fairness 

would be frustrated if AstraZeneca's unsupported pleas for additional Markman briefing were 

countenanced. Hanmi respectfully asks that no additional Markman briefing or discovery be 

permitted and that the hearing date be scheduled at the Court's earliest convenience as requested 

in Hanmi's January 13, 2012 letter. 

Respectfully, 

/s/ Allyn Z. Lite

Allyn Z. Lite 

AZL:emp 

cc: Hon. Joel A. Pisano, U.S.D.J. (via ECF) 

 All Counsel of Record (via ECF) 

 

 

3

 Hoffman-LaRoche Inc. v. Apotex., C.A. No. 07-4417, D.I. 397 (D.N.J. Dec. 29, 2011), relied 

upon by AstraZeneca in support of the present motion, is irrelevant both factually and legally. 

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