LITE DEPALMA GREENBERG, LLC

Allyn Z. Lite

Michael E. Patunas

Mayra V. Tarantino

Two Gateway Center, 12th Floor

Newark, New Jersey 07102

Telephone: (973) 623-3000

Facsimile: (973) 877-3872

alite@litedepalma.com

mpatunas@litedepalma.com

mtarantino@litedepalma.com

Attorneys for Defendants Hanmi USA, Inc.,

Hanmi Pharmaceutical Co., Ltd., Hanmi Fine 

Chemical Co., Ltd., and Hanmi Holdings Co., 

Ltd.

UNITED STATES DISTRICT COURT 

DISTRICT OF NEW JERSEY

ASTRAZENECA AB, AKTIEBOLAGET 

HÄSSLE, ASTRAZENECA LP, KBI INC., 

and KBI-E INC.,

Plaintiffs and 

 Counterclaim Defendants,

v.

HANMI USA, INC., HANMI 

PHARMACEUTICAL CO., LTD., HANMI 

FINE CHEMICAL CO., LTD, and HANMI 

HOLDINGS CO., LTD.,

Defendants and 

 Counterclaim Plaintiffs. 

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Civil Action No. 3:11-CV-00760-JAP-TJB

SUPPLEMENTAL DECLARATION OF JERRY L. ATWOOD, Ph.D. 

I, Jerry L. Atwood, state and declare as follows:

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1. I make this declaration in further support of my Declaration of November 3, 2011, 

which was prepared in conjunction with Hanmi’s initial Markman submission in the abovecaptioned matter. I incorporate herein the substance of my previous Declaration, including my 

background, the scope of my review, and the credentials of a person of ordinary skill in the art. 

2. Further to the materials I have relied upon previously, I have considered the 

November 7, 2011 Declaration of Stephen G. Davies (D.I. 133-3) and exhibits attached thereto, 

prepared in conjunction with AstraZeneca’s Initial Markman Brief. I have also considered Dr. 

Davies’ Declaration, deposition transcript and related exhibits, as well as the additional 

materials referred to in this declaration.

A. Issues Regarding “Salt” Scope In Both Patents

“alkaline salt” -- ‘504 patent

3. Each of claims 1, 6 and 7 of the ‘504 patent calls for an “alkaline salt” of (-)-

omeprazole. For the reasons set forth in my previous Declaration, those salts are “Na+, Mg2+, 

Li+

, K+, Ca2+ or N+(R)4 salt” where R is an alkyl with 1-4 carbon atoms. In addition, I 

understand that AstraZeneca has now asserted claims 3, 5, and 10 in this litigation. 

4. Claim 3 recites the pharmaceutical formulation of claim 1, wherein the alkaline salt 

is a Na+

, Mg2+, Li+, K+, Ca2+ or N+(R)4 salt. Claim 5 recites the pharmaceutical formulation of 

claim 1, wherein the alkaline salt is a sodium or magnesium salt. Claim 10 recites the method 

of claim 6 or 7 wherein the alkaline salt is a Na+, Mg2+, Li+, K+, Ca2+ or N+(R)4 salt. 

5. Dr. Davies has stated that the term “alkaline salt” means any basic salt that is 

suitable for use in a pharmaceutical formulation. I disagree that the “alkaline salt” as claimed in 

the ‘504 patent can include any basic salt and that the patent requires that the salt be suitable for 

use in a pharmaceutical formulation. 

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Any Basic Salt

6. Dr. Davies defines “alkaline salts” of the claims as “any basic salt” and includes 

within his definition all of the Group I and Group II metals, as well as the ammonium salt, NH4

+ 

and others. (Davies Decl. ¶ 36; Davies Tr. 149-151 (Ex. 1).) His Declaration states:

a person of ordinary skill would understand that suitable cations 

for “alkaline salts” 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, which is often considered an honorary alkaline salt 

because ammonia, when dissolved in water, affords a basic 

solution. (Davies Decl. ¶ 36.)

7. In support, Dr. Davies cites the Chambers Dictionary of Science and Technology, 

which defines “alkali metals” to mean “lithium, sodium, potassium, rubidium, and caesium, all 

monovalent metals in the first group of the periodic system;” and defines “alkaline earth metals” 

to mean “beryllium, magnesium, calcium, strontium, barium, and radium, all divalent metals in 

the second group of the periodic system.” (Davies Decl., p. 11 at n. 1.) 

8. Broadly, Dr. Davies explained that all alkaline salts would be included within his 

definition (Davies Tr. 161-162; 172), which number in the hundreds of thousands or even 

millions (Davies Tr. 147-148). 

9. For example, in addition to the N+(R)4 salts described in the specification (where R is 

an alkyl group with 1-4 carbon atoms), Dr. Davies also includes within his definition of 

“alkaline salts” N+(R)4 salts, where R is an alkyl group having more than 1-4 carbon atoms, 

e.g., 5, 6, 7 or greater. (Davies Tr. 157.)

10. Dr. Davies also includes within his definition of “alkaline salts” certain amines such 

as pentamethyl guanidine salts and guanidinium salts, but excludes other amines such as 

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pyridine or piperadine salts. (Davies Tr. 158-159; 170-171.) He excludes amino acids salts 

from his definition of “alkaline salts.” Id.

11. Dr. Davies further includes within his definition of “alkaline salts” all metals and he 

stated that there are a lot of metals. (Davies Tr. 160.) 

12. For the reasons stated in my initial declaration, the term “alkaline salts” is properly 

defined as the five inorganic species and the one organic genus described in the ‘504 patent 

specification, and I disagree that the intrinsic record of the ‘504 patent supports the broad, 

sweeping definition of “alkaline salt” advanced by Dr. Davies.1 There is no disclosure in the 

‘504 patent suggesting that the alkaline salts of the claimed pharmaceutical formulations could 

possibly include all metal salts, all Group I and Group II elements salts, ammonium and all 

tetraalkyl ammonium salts, pentamethyl guanidine salts and guanidinium salts, or any basic salt. 

There is no disclosure in the ‘504 patent of how to make or use the universe of basic salts 

described by Dr. Davies. The structure and properties of the hundreds of thousands of salts are 

so widely varied that no person skilled in the art would view the disclosure of the six recited 

species as representative of all alkaline salts as defined by Dr. Davies. To the contrary, persons 

skilled in the art would know that many of the salt species included with Dr. Davies’ definition 

are neither disclosed in the ‘504 patent, “suitable for use in pharmaceutical formulations,” nor is 

any method provided for making them. 

13. For example, Dr. Davies states clearly that rubidium, cesium, beryllium, and barium 

would be understood as included within the definition of “alkaline salt.” (Davies Decl. ¶ 36.)

 1 The ‘504 patent states that “the present invention refers to the new Na+

, Mg

2+, Li+

, K+., Ca2+or 

N+(R)4 salts of the single enantiomers of omeprazole.” (Col. 2, ll. 42-49). Dr. Davies testified 

he did not specifically consider this teaching of the ‘504 patent in formulating his definition of 

“alkaline salts.” (Davies Tr. 155-156.)

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14. Beryllium is highly toxic, especially by inhalation, and reported as a known 

carcinogen by OSHA.2 Beryllium intoxication has been reported to cause pneumonitis and 

osteosarcoma in animals as well as bone tumors in humans. 3 Other authors confirm the 

extreme toxicity of beryllium:

Beryllium causes chronic beryllium disease (CBD), which is a fatal 

disease of the 20th century and has been confirmed in eight cases 

by lung biopsy and the blood beryllium lymphocyte proliferation 

test (Be LPT). It also causes a number of diseases such as 

bronchitis, pulmonary granulomatosis and hepatomegaly, because 

the liver is the target organ of beryllium. Its accumulation causes 

cellular death. Beryllium also interacts with DNA and causes gene 

mutation, chromosomal aberration and sister chromatid exchange 

in cultured somatic cells. [footnotes omitted].4

15. No one skilled in the art would expect beryllium to be an “alkaline salt” of the ‘504 

patent claims.

16. Cesium is a Group I element that has certain chemical properties similar to 

potassium, sodium, and lithium. Dalal, et al., report that cesium chloride has antineoplastic 

properties, but that patients taking cesium chloride as an anticancer compound acquired QT 

prolongation and sustained monomorphic ventricular tachycardia.5 Yung also reports that 

cesium is a carcinogen, and that an excess of cesium can cause neuromuscular toxicity and 

convulsions.6

 2 GESSNER G. HAWLEY, THE CONDENSED CHEMICAL DICTIONARY (Van Nostrand Reinhold Co.) 

(10th ed. 1981). (Ex. 3.) 

3 Christoph Y. Yung, A Synopsis on Metals in Medicine and Psychiatry, 21:1 PHARMACOLOGY 

BIOCHEMISTRY & BEHAV. 41-47 (1984). (Ex. 4.)

4 Pragya Sharma et al., Beryllium-induced Toxicity and its Prevention by Treatment with 

Chelating Agents, 20 J. APPLIED TOXICOLOGY 313-18 (2000). (Ex. 5.)

5 Anuj K. Dalal et al., Acquired Long QT Syndrome and Monomorphic Ventricular Tachycardia 

After Alternative Treatment With Cesium Chloride for Brain Cancer, 79:8 MAYO CLINIC PROC.

1065-69 (2004). (Ex. 7.)

6 See Yung, discussed above in footnote 3.

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17. Even though beryllium and cesium are Group I and II metals7 and within Dr. Davies’ 

definition of alkaline salts in the context of the ‘504 patent claims, a person of ordinary skill 

would not view either element as a suitable alkaline salt of the ‘504 patent due to their high 

toxicities. 

18. Francium is a Group I element that exists only as radioactive isotopes and although it 

was not mentioned specifically in his Declaration, it is within Dr. Davies’ definition of “at least, 

cations of all the metals in Groups I and II . . . .” Francium 223 is the longest lived of the 

isotopes, and has a half-life of 21 min. Francium is the heaviest of the alkali metal family.8 

Based on its short half-life and radioactivity, a person skilled in the art would not view francium 

as a suitable alkaline salt of the ‘504 patent.

19. Radium is another radioactive element of Group II and is within the scope of Dr. 

Davies’ definition. (Davies Decl. ¶36 and note 1.) Radium is defined as highly toxic and emits 

ionizing radiation. It is destructive to living tissue and used in industrial radiography. Persons 

of skill in the art would not view radium as a suitable alkaline salt of the ‘504 patent.9

20. Rubidium is also a Group I element. Yung reports that an excess of rubidium can 

cause tetany, convulsion, and death.10

21. Barium is a Group II element that is used medically in preparations as a radio 

contrast medium. Its toxic effects are reported as including gastrointestinal symptoms, 

convulsions, hypertension, and cardiac arrest.11 

 7

 A copy of the Periodic Table of Elements is provided as Ex. 13.

8 GESSNER G. HAWLEY, THE CONDENSED CHEMICAL DICTIONARY (Van Nostrand Reinhold Co.) 

(10th ed. 1981). (Ex. 3.)

9 Id.

10 See Yung, discussed above in footnote 3.

11 Id.

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22. Due to the toxicities of these compounds, persons of skill in the art would not view 

rubidium or barium as suitable alkaline salts of the ‘504 patent.

23. Indeed, if the group of alkaline salts includes all metals as Dr. Davies testified 

(Davies Tr. 160), he has swept in numerous toxic metals from across the periodic table. Persons 

of ordinary skill in the art would understand that most metals referred to by Dr. Davies are toxic 

at a level required to achieve a pharmaceutical effect of (-)-omeprazole. For example, 

administration of a lead salt to humans would have disastrous consequences.

24. In addition to the toxicity and unsuitability of many of the alkaline salts included 

within Dr. Davies’ definition, a person of ordinary skill in the art would not know if many of the 

other undisclosed salts included within his definition could even be prepared, or how to do so.

25. The ‘504 patent provides two different procedures of how to make inorganic salts 

and does not inform one skilled in the art how or why to select one procedure over another. 

Specifically, the patent generally discloses the preparation of the sodium, lithium and potassium 

salts of (-)-omeprazole according to one general procedure (Col. 4, ll. 51-61 (D.I. 86-2)), and 

preparation of the magnesium and calcium salts of (-)-omeprazole from a different procedure --

starting with the sodium salt of (-)-omeprazole (Col. 4, ll. 63- Col. 5, l. 6).

26. The ‘504 patent fails to explain why some salts of (-)-omeprazole are prepared using 

a metal salt hydroxide and the free base of (-)-omeprazole and other salts are only prepared 

from the sodium salt previously made according to this first general procedure. The ‘504 patent 

does not direct those skilled in the art which procedure should be used to prepare other, 

undisclosed salt species.

27. Further, the ‘504 patent makes clear that the process of the working Examples results 

in the conversion of one enantiomer to the other (+ to - and - to +) during preparation of the 

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sodium salts of (-)-omeprazole from the neutral form, and as well for the preparation of the 

magnesium salt from the sodium salt. (Col. 6, ll. 29-35.) Preparation of the (+)-omeprazole 

salts thus requires (-)-omeprazole or its salts as a starting point, and vice versa. The disclosure 

is specific as to preparation of the magnesium and sodium salts only, and there is no way to 

know whether chiral inversion would occur with any other alkaline salt.

28. As a result, persons skilled in the art would be unable to determine which procedure 

to use in preparing future alkaline salts of (-)-omeprazole (undisclosed in the ‘504 patent), and 

whether chiral inversion would necessitate selection of the opposite enantiomer as a starting 

material. In my view, the ‘504 patent disclosure of the preparation of only two species does not 

demonstrate that all of the possible genus members could be made in a similar way. 

29. In defining “alkaline salts” as including salts such as pentamethyl guanidine salts 

and guanidinium salts, but excluding other amines such as pyridine or piperadine salts, as well 

as amino acids (Davies Tr. 158-159; 170-171), Dr. Davies explained that not all organic cationic 

species form alkaline salts with (-)-omeprazole, but rather, only those organic compounds that 

form strong bases. Id. There is no disclosure in the ‘504 patent of alkaline salts of (-)-

omeprazole that are selected based on their strengths as bases. Nothing in the patent or 

prosecution history supports Dr. Davies’ view that only strong bases would be appropriate for 

the formation of alkaline salts of (-)-omeprazole. Nor does Dr. Davies provide any criteria for 

determining the basic strength of an organic compound sufficient for persons of ordinary skill in 

the art to know whether that compound would be an “alkaline salt” of (-)-omeprazole as 

claimed.

30. As a further example, there is no explanation in the ‘504 patent as to how to prepare 

any of the ammonium salts that are described in the patent (N+(R)4), and a person of skill in the 

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art would not know whether ammonium salts could be prepared from the same methods as were 

used to prepare the inorganic salts of Examples 1-7, or would require different methods. At his 

deposition, I see that Dr. Davies expressed doubt as to whether or not an ammonium salt of (-)-

omeprazole could even be formed.12 (Davies Tr. 151-153.) Dr. Davies suspects that a 

tetrabutyl ammonium salt of (-)-omeprazole could be formed, but he doesn't know whether it 

would be a solid salt. (Davies Tr. 153-154.) On these points, I agree with Dr. Davies, because 

there is simply not enough information in the ‘504 patent for a person of ordinary skill in the art 

to know how, or whether, ammonium salts of (-)-omeprazole could even be formed.

31. Dr. Davies stated in an earlier declaration relating to (-)-omeprazole, that salt 

formation “may be a possibility for some compounds or mixtures, but would not be possible for 

many others.” He added that a skilled person would have no means of knowing whether it 

would or would not work. He concluded that salt formation “would not be the first [method] 

contemplated by a skilled person, because the skilled person would have no expectation that 1) 

a salt of the enantiomer of omeprazole could be formed.” (Davies Tr. at 176-178; Davies Dep. 

Ex. 10, p. 25, HAN0043425 (Ex. 6).) These prior statements in earlier declarations are 

inconsistent with Dr. Davies present statements that virtually any basic salt could be made and 

would satisfy the definition of “alkaline salt” in the ‘504 patent claims.

32. I agree with these earlier statements of Dr. Davies. Because persons of ordinary skill 

in the art “would have no expectation that 1) a salt of the enantiomer of (-)- omeprazole could 

be formed,” they certainly would not be able to prepare all of the undisclosed alkaline salts of 

(-)-omeprazole Dr. Davies now urges are included within the scope of the claims. 

 12 Dr. Davies appears to take the unusual position that if a particular alkaline salt can be formed, 

then it is within the scope of his definition. If it cannot be formed, then it appears to be 

excluded. (Davies Tr. 152.) I do not believe this is a proper methodology for determining the 

scope of the claims.

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Suitable for use in a pharmaceutical formulation

33. Based only on the language of the claims, Dr. Davies construes that the “alkaline 

salts” are those “suitable for use in a pharmaceutical formulation.” (Davies Decl. ¶41.) 

However, during his deposition, he plainly conceded that one of ordinary skill in the art would 

need to perform experimentation to determine if his vast field of potential salts would – in fact –

be pharmaceutically acceptable. (Davies Tr. at 173-174.) This entire concept of having to test 

potential salts is far afield from any aspect of the intrinsic record. There is nothing about the 

type of testing, the methodology, the standards used to determine alleged suitability, etc. in the 

‘504 patent. AstraZeneca and Dr. Davies graft entire new concepts requiring nebulous testing 

in order to determine the scope of the claims. This practice simply does not comport with the 

manner in which a person of ordinary skill in the art determines claim scope. 

34. Nothing in the claims of the ‘504 patent, specification, or prosecution history 

requires that the alkaline salt independently be suitable for use in a pharmaceutical formulation. 

For example, claim 1 recites “a pharmaceutical formulation” and a “pharmaceutically 

acceptable carrier.” The term “alkaline salt” is not modified by the terms “pharmaceutical” or 

“pharmaceutically acceptable.” Thus, when the ‘504 patentees wanted to claim a formulation or 

a component of a formulation as “pharmaceutically acceptable,” they certainly knew how to do 

so. That they chose not to describe the alkaline salt of claim 1 as such, informs that the correct 

construction of “alkaline salt” does not require the pharmaceutical limitation as suggested by 

Dr. Davies.

35. Moreover, in terms of determining “suitability” according to Dr. Davies’ theoretical 

test protocol, no disclosure exists in the ‘504 patent that describes how “suitability” is 

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measured, or which tests are used, or which standards are used. Adding this type of requirement 

to the meaning of “alkaline salt” would inject multiple layers of ambiguity. 

36. Similarly, nowhere in the patent specification or prosecution history is it defined or 

required that the alkaline salt independently be suitable for use in a pharmaceutical formulation. 

For example, the patent specification refers to pharmaceutically acceptable carriers, 

pharmaceutically acceptable enteric coating materials, and pharmaceutically acceptable 

solvents. These descriptions show that the ‘504 patentees knew how to describe individual 

components of a formulation as pharmaceutically acceptable. That they chose to require other 

components of the formulation to be “suitable for use in a pharmaceutical formulation,” -- but 

not alkaline salts -- demonstrates that the term “alkaline salt” is not so limited.

37. While the carrier must be pharmaceutically acceptable, and the overall formulation is 

a pharmaceutical one, nothing in the intrinsic evidence of the ‘504 patent requires that the 

“alkaline salt” be independently suitable for pharmaceutical administration.

38. Contrary to Dr. Davies’ opinion, it does not necessarily follow that a pharmaceutical 

formulation of claim 1 necessarily requires that the alkaline salt also be independently suitable 

for use in a pharmaceutical formulation. In some cases alkaline salts of pharmaceutical 

compounds can be otherwise unsuitable, but the formulation as a whole -- including the active 

pharmaceutical ingredient and all other components – can be made to be pharmaceutically 

acceptable. 

39. For example, potassium salts have been considered unsuitable for oral formulations 

such as suspensions and syrups because of their bitter taste. However, when taste masked with 

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sweeteners or other agents, the potassium salt of an active pharmaceutical ingredient can be 

made suitable for pharmaceutical administration.13

40. In another example, a poorly water-soluble alkaline salt of a pharmaceutical 

compound can be made to be suitable for use as a pharmaceutical formulation by increasing its 

water solubility through formulation techniques. Nimesulide is a potent nonsteroidal antiinflammatory drug successfully used for the treatment of different inflammatory conditions and 

rheumatoid arthritis. U.S. Pat. No 5,744,165 (Nimesulide Salt Cyclodextrin Inclusion 

Complexes) (Ex. 8) reports that nimesulide is practically insoluble in water (Col. 1, ll. 51-55), 

and while the alkaline and alkaline earth salts of nimesulide were more water-soluble, the patent 

states that “due to the high pH value of their solutions, the nimesulide alkali and alkaline earth 

salts were not practical for use as pharmaceuticals” (Col. 1, ll. 39-41). To remedy these 

problems, the ‘165 patent is directed to increasing the water solubility of alkaline salts of 

nimesulide by forming inclusion complexes with cyclodextrins. By formulating differently, 

patentees were able to transform unsuitable alkali/alkaline earth metal salts of nimesulfide into 

those suitable for use in pharmaceutical formulations .

41. These examples confirm the understanding of a person of ordinary skill in the art, 

that an alkaline salt -- otherwise unsuitable for use in a pharmaceutical formulation for any one 

of a variety of reasons -- can be made to be suitable by formulation, modification and other 

techniques. For these reasons, I disagree that the term “alkaline salt” in the ‘504 patent includes 

any limitation directed to pharmaceutical acceptability. 

42. In an earlier litigation against DRL, I understand that Astra Zeneca proposed a 

construction of “alkaline salt” that is different than the construction it proposes in the present 

 13 See Berge (1977) describing potassium salts as exhibiting “inferior palatability.” D.I. 112-4 at 

9 (left col.) and other taste-masking examples discussed at pp. 4, 8.

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case. Specifically, I understand AstraZeneca did not previously propose that the term “alkaline 

salt” as used in the claims of the ‘504 patent contained a limitation that they be “suitable for use 

in a pharmaceutical formulation,” and of course, they do so presently. Dr. Davies explained at 

his deposition that – in the previous DRL case – he was defining alkaline salt, whereas in the 

present case, he is defining an alkaline salt in the context of claim 1. (Davies Tr. 80-81.) That 

distinction is unclear and nonsensical to me because in both cases the term “alkaline salt” at 

issue was and is in claim 1 of the ‘504 patent asserted by AstraZeneca.

“pharmaceutically acceptable salt” – ‘192 patent

43. The ‘192 patent specification makes clear that the term “pharmaceutically acceptable 

salt” refers to both acid and alkaline pharmaceutically acceptable non-toxic salts. 

(‘192 patent, col. 4, ll. 13-16.) As I stated in my previous Declaration, that definition would be 

considered dominant and controlling by a person of ordinary skill in the art.

44. Notwithstanding this express definition, Dr. Davies urges that the “acid” salts of this 

definition do not apply to (-)-omeprazole as the active pharmaceutical ingredient, but rather, 

apply only to the other therapeutic ingredients referred to in this paragraph. (Davies Decl. ¶¶ 

65, 66.) I disagree with Prof. Davies’ interpretation.

45. Preceding the express definition of “pharmaceutically acceptable salt” is a sentence 

that states:

The pharmaceutical compositions of the present invention comprise 

the (-)-enantiomer of omeprazole as active ingredient, or a 

pharmaceutically acceptable salt thereof, and may also contain a 

pharmaceutically acceptable carrier and optionally, other 

therapeutic ingredients.

46. There is little question but that the pharmaceutically acceptable salt thereof refers to 

the (-)-enantiomer of omeprazole, and nothing else in that sentence -- either the 

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pharmaceutically acceptable carrier or the other therapeutic ingredients. Dr. Davies’ strained 

reading of this passage is simply unsound and would be at odds with how one of ordinary skill 

in the art would interpret this plain passage.

47. For example, he posits that the “other therapeutic agents” need not be limited to 

alkaline salts, and may be employed as acid addition salts. (Davies Decl. ¶ 66.) There is no 

support for this explanation, for at least the following reasons:

x there are no “other therapeutic agents” disclosed anywhere in the ‘192 

patent and so there is no basis to conclude that salts of those agents 

could even be formed,

x nor is there any way to conclude that the “other therapeutic agents” 

can form acid salts in particular, in a way that supports Dr. Davies 

hypothesis, and 

x “pharmaceutically acceptable salt” is only used in connection with(-)-

omeprazole, and never in conjunction with other therapeutic agents.

48. In support of his arguments that alkaline salts are basic salts that are made under 

basic conditions, Dr. Davies appears to state that (1) acidic conditions cannot be used to prepare 

the enantiomers of (-)-omeprazole (Davies Decl. ¶¶ 48, 67) and that (2) acid addition salts of 

(-)-omeprazole could not exist because they would be inherently unstable. Id. I disagree with 

both propositions. 

49. Referring to the DE ‘455 German reference (“the Kohl reference”) (D.I. 111-2, 

HAN0039827-844), which is the reference alluded to by Dr. Davies in paragraphs 48 and 67, 

the ‘504 patent specification describes the preparation of the enantiomers of omeprazole by 

preparing diastereomers of racemic omeprazole, separating the diastereomers, and hydrolyzing 

the ester portion off, to obtain the isolated enantiomers. (Col. 1, ll. 26-42.) Both the Kohl 

reference and the ‘504 patent specification, describe that the hydrolysis step used to obtain the 

enantiomers is carried out in concentrated sulfuric acid. In order to avoid degradation, the 

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acidic solution is neutralized with concentrated sodium hydroxide. While this procedure would 

be disadvantageous commercially because it is highly exothermic, neither the Kohl reference 

nor the ‘504 patent states that the prior art was unsuccessful in preparing optically pure 

enantiomers of omeprazole as stated by Dr. Davies. (Davies Decl. ¶ 67.) 

50. To the contrary, the Kohl reference makes clear that the (+)-enantiomer of 

omeprazole was obtained -- under acidic conditions -- as an amorphous solid product having an 

optical rotation of >Į@23D = +165o. (D.I. 111-2 at HAN0039593 (Example 6)). This value is 

higher than the optical rotation value reported in the ‘504 patent for (+)-enantiomer of 

omeprazole formed in Example 13. It is generally well-known that the higher the absolute 

value of the optical rotation is, the more optically pure the sample is. 

51. Both the ‘504 patent and the Kohl reference make clear that acidic conditions can be 

used to prepare the enantiomers of omeprazole.

52. In addition, acid salts of the (-)-enantiomer of omeprazole can certainly be prepared 

and they are not inherently unstable. Dr. Davies concedes that acid salts indeed can be formed: 

“(-)-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.” (Davies 

Decl., D.I. 133-3, ¶ 38 at p. 13.) In paragraph 39 of his declaration, Dr. Davies illustrates 

formation of an alkaline salt, and then in paragraph 40, the formation of an acid salt of (-)-

omeprazole is depicted. Id. at 14. Thus, I disagree with Dr. Davies’ statements that those 

skilled in the art would understand “pharmaceutically acceptable salt” in the ‘192 patent to refer 

only to alkaline salts and not to acid addition salts (Davies Decl. ¶¶ 67-68) as plainly incorrect 

and unsupported.

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53. The relevant scientific literature clearly establishes that acid addition salts of 

omeprazole can be made and are stable. AstraZeneca’s U.S. Patent No. 4,337,257 (Ex. 9), 

issued June 29, 1982, and discloses acid addition salts of omeprazole:

Depending on the process conditions and the starting materials, the 

end product is obtained either as the free base or in the acid addition 

salt, both of which are included within the scope of the invention. 

Thus, basic, neutral or mixed salts may be obtained as well as hemi, 

mono, sesqui or polyhydrates. The acid addition salts of the new 

compounds may in a manner known per se be transformed into free 

base using basic agents such as alkali or by ion exchange. On the 

other hand, the free bases obtained may form salts with organic or 

inorganic acids. In the prepartion of acid addition salts preferably 

such acids are used which form suitable therapeutically acceptable 

salts. Such acids include hydrohalogen acids, sulfonic, phosphoric, 

nitric, and perchloric acids; aliphatic, alicyclic, aromatic, 

heterocyclic carboxy or sulfonic acids, such as formic, acetic, 

propionic, succinic, glycolic, lactic, malic, tartaric, citric, ascorbic, 

maleic, hydroxymaleic, pyruvic, phenylacetic, benzoic, paminobenzoic, antranilic, p-hydroxybenzoic, salicylic or paminosalicylic acid, embonic, methanesulfonic, ethanesulfonic, 

hydroxyethanesulfonic, ethylenesulfonic, halogenbenzenesulfonic, 

toluenesulfonic, naphthylsulfonic or sulfanilic acids; methionine, 

tryptophane, lysine or arginine. 

These or other salts of the new compounds, as e.g. picrates, may 

serve as purifying agents of the free bases obtained. Salts of the 

bases may be formed, separated from solution, and then the free 

base can be recovered from a new salt solution in a purer state. 

Because of the relationship between the new compounds in free 

base form and their salts, it will be understood that the 

corresponding salts are included within the scope of the invention.14

(Ex. 9; Col. 5, ll. 17-40).

54. Other references clearly establish the existence of acid addition salts of omeprazole. 

For example, omeprazole hydrochloride is a prior art compound disclosed in U.S. Patent No. 

5,066,652 (1991) (Ex. 10). Obviously, if the prior art taught how to make acid salts of 

omeprazole, acid salts of the enantiomers of omeprazole could be made by the same techniques.

 14 AstraZeneca’s U.S. Patent Nos. 4,255,431 and 4,508,905 contain identical disclosure.

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55. U.S. Patent 6,255,502 (2001) (Ex. 11) specifically discloses capric acid and lauric 

acid salts of omeprazole and methods for making those salts.

56. M. Karthikeyan et al.15 disclose formulation experiments on omeprazole 

hydrochloride purchased from a commercial source. Dr. Davies unsupported conclusions that 

persons of ordinary skill in the art would not understand pharmaceutically acceptable salts of 

(-)-omeprazole to include acid addition salts is squarely contradicted by AstraZeneca’s own 

earlier patents, and other references, showing the preparation of various omeprazole acid salts.

B. Issues Regarding Optical Purity In Both Patents

“(-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2- 

pyridinyl)methyl]sulfinyl]-1H-benzimidazole” – ‘504 patent independent claims 1, 6 

and 7 and “optically pure” – dependent claim 2

57. I understand that AstraZeneca stands by its representations to the Court in AZ v. DRL 

action and views the resulting constructions as correct. For the reasons set forth in my 

Declaration of November 3, 2011 (¶¶ 27-48), I remain of the view that the ‘504 patent 

specification and prosecution history do not support adding numerical limitations to any of the 

‘504 or ‘192 patent claims.

58. I have reviewed Dr. Davies’ opinions provided in his November 7, 2011 Declaration 

Appendix on issues concerning optical purity in both patents. As a general matter, Dr. Davies, 

as with AstraZeneca’s previously articulated claim construction arguments, dismisses the 

unambiguous express language of the ‘504 patent -- defining the “optically pure” Na salts of 

omeprazole as “the (+)-enantiomer of omeprazole Na-salt essentially free of the (-)-enantiomer 

of omeprazole Na-salt and the (-)-enantiomer essentially free of the (+)-enantiomer, 

respectively.” (Col. 3, ll. 30-35.)

 15 M. Karthikeyan et al., Formulation and Comparative Studies of Diclofenac With Omeprazole 

and Diclofenac With Pantoprazole, 1:1 J. PHARM. & BIOMEDICAL SCIS. 1-4 (2010) (Ex. 12).

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59. Instead, Dr. Davies relies essentially solely on the Examples of the ‘504 patent to 

read lower numerical limits into the claims, which is improper for the reasons set forth in my 

earlier Declaration. Dr. Davies fails to explain why the patent “examples” function to narrow 

and confine the scope of the claims, in violation of the clear language of the patent which states 

the opposite is true. As I explained in my previous declaration, the ‘504 specification prefaces 

the Examples with the following unambiguous statement:

The invention is illustrated by the following examples using preferred 

procedures for the preparation of optically pure sodium salts and 

magnesium salts. ‘504 patent, col. 6, ll. 26-28 (emphasis added). 

60. Dr. Davies considered this language and opined that the use of the term “illustrated” 

signaled a limiting definition of the optical purity of the claimed compounds based strictly on 

the examples that followed this statement. (Davies Tr. 209-210.) I disagree that examples

illustrating an invention using only preferred procedures for preparation provide limiting 

definitions of claimed features. 

61. Dr. Davies’ improper methodology for importing limitations of the Examples into 

the claims begins with his explanation of the prior art 1990 Erlandsson publication, which is 

discussed in the background section of the ‘504 patent (col. 1, ll. 27-29) (Davies Decl. 

Appendix ¶¶ 7-9). According to Dr. Davies, the “patent provides (-)-omeprazole at an optical 

purity not provided by prior art methods.” (Davies Decl. Appendix ¶ 6.) Because the 

Erlandsson reference disclosure of (-)-omeprazole in an optical purity of 95.6% (91.2% e.e.) is 

prior art, Dr. Davies concludes that the ‘504 patent claims cannot be construed to include 

compounds having optical purity at the levels disclosed in the Erlandsson reference, even 

though (1) the express definition of optically pure in the ‘504 patent is not defined by a 

numerical value; and (2) none of the claims contained a numerical value as a limitation on 

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optical purity. I disagree with Dr. Davies’ methodology as well as his reading of the Erlandsson 

reference.

62. First, there is no dispute that the Erlandsson reference is directed to the separation of 

racemic omeprazole into its enantiomers, which are obtained in neutral form, i.e., as free bases 

and not as salts as recited in the asserted claims 1-7 and 10 of the ‘504 patent. Distinguishing 

the claimed salts of (-)-omeprazole from the prior art disclosures of the neutral forms, the ‘504 

patent states:

There is no example in the known prior art of any isolated or characterized 

salt of optically pure omeprazole, i.e. of single enantiomers of omeprazole or 

of any isolated or characterized salt of any optically pure omeprazole 

analogue. (Col. 1, ll. 43-47.)

63. This statement makes clear the patentees’ view that that the prior art did not disclose 

any salt of optically pure omeprazole whether as a single enantiomer or as an analog thereof. 

Because the asserted salt claims of the ‘504 patent do not encompass the neutral form of 

omeprazole’s enantiomers, there is no connection with or reason to limit the optical purity of the 

claimed salts based on a prior art disclosure of neutral forms of the single enantiomers. A 

person skilled in the art would simply not understand that the optical purity of the claimed salts 

is in any way limited or defined by the optical purity of the prior art enantiomers in neutral 

form.

64. Even if the Erlandsson reference disclosure of (-)-omeprazole neutral form having an 

optical purity of 91.2% e.e. were relevant to the interpretation of the ‘504 patent claims (which 

it is not), Dr. Davies provides no reason why the lower limit of optical purity of the claimed 

salts of (-)-omeprazole is 94% e.e., or why salts of (-)-omeprazole having an optical purity of, 

e.g., between 91.2% e.e. and 94% e.e. would be outside the scope of the claims lacking any 

purity limitation at all. In fact, the only disclosure of 94% e.e. is in Example 12, which is the 

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neutral form of (-)-omeprazole and not its salt. The ‘504 patent does not have any disclosure 

whatsoever linking the optical purity of any salt form to 94% e.e.

65. Dr. Davies’ methodology of (1) selecting as a starting point the prior art disclosure 

of the neutral form (-)-omeprazole as a basis for establishing a lower limit on the optical purity 

of the claimed salts, (2) arbitrarily importing the 94% optical purity value of the neutral form 

from Example 12 into the salt claims, and (3) failing to explain how or why compounds having 

an optical purity between 91.8% e.e. and 94% e.e. would not be included within the scope of the 

claims is flawed and unsupported.

66. In addition, Dr. Davies ignores the Erlandsson reference's teaching of (+)-

omeprazole, obtained at an enantiomeric purity of 82% (64% e.e.) (D.I. 133-5 at 317), and fails 

to explain why (even using his own flawed methodology) he did not consider the optical purity 

of the (+)-enantiomer in determining the lower limit of the ‘504 patent claims. I believe it is 

inconsistent for Dr. Davies to have repeatedly relied on Examples 1, 3, 4 and 7 of the ‘504 

patent (all directed to salts of (+)-omeprazole) to support his views about the interpretation of 

the claims, but to have wholly disregarded the prior art teachings of (+)-omeprazole in the 

Erlandsson reference in arbitrarily concluding the lower limit of the optical purity of the salts of 

claim 1 is 94% e.e.

67. Further, as I stated in my initial Declaration and explained at my deposition, the 

optical purities of the neutral forms of (-)-omeprazole in Example 12 and in the Erlandsson 

reference neither support nor limit the optical purities of the alkaline salts of (-)-omeprazole in 

the claims. (Atwood Decl. ¶¶ 34-35; Atwood Tr. 190; 194-97; 222-24 (Ex. 2).) The 

enantiomers of omeprazole in non-salt or neutral form are not part of the invention of the ‘512 

application as filed, because they were admittedly known in the prior art. There is no basis to 

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limit the optical purity of a claimed (-)-omeprazole salt based on the prior art disclosure of the 

optical purity of a single enantiomer in neutral form.

68. Dr. Davies urges that “optically pure” of Claim 2 means at least 98% e.e. I disagree 

with his flawed methodology of limiting “optically pure” in the claims based on measured 

values for compounds reported in the Examples. Even using his methodology, none of the 

examples support a 98% e.e. limitation. The closest value in the examples provided by the 

Examples for a (-)-omeprazole salt is 98.4% in Example 6, and Prof. Davies has not explained 

how the claims could encompass compounds having an optical purity between 98.0 - 98.4% 

e.e., particularly given his views about the optical purity of the neutral form in Example 12. 

The only example of a salt form at 98% e.e. is for a (+)-enantiomer (Example 3).

69. Dr. Davies’ inconsistent and selective reliance on the teachings of the Erlandsson 

reference and the ‘504 patent Examples further supports my conclusion that there is nothing in 

the ‘504 patent documents which support adding any numerical limitations into the ‘504 claims, 

let alone the 94% -98% e.e. values for salts according to the patent.

70. With respect to the ‘192 patent claims which encompass both the neutral form of the 

(-)-enantiomer and pharmaceutically acceptable salts thereof, Dr. Davies asserts that the ‘504 

patent specification can be used to assign a lower optical purity limit of 98% e.e. In fact, there 

is no disclosure in the ‘504 patent of a neutral form of a (-)-enantiomer having an optical purity 

of 98%. The only example of a free enantiomer reported as 98% e.e. is Example 13 directed to 

a (+)-enantiomer. And as pointed out above, there is no disclosure in the ‘504 patent of a (-) 

salt having an optical purity of 98% e.e. Thus, even under the improper methodology of 

limiting the claims to numerical values found only in illustrative working examples – based on 

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