UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`
`APOTEX INC.,
`Petitioner,
`
`v.
`
`CELGENE CORPORATION,
`Patent Owner
`
`____________________________________________
`
`Case IPR2023-00512
`Patent 8,846,628
`____________________________________________
`
`EXPERT DECLARATION OF JEFFREY ETTER, PHD
`
`CELGENE 2054
`APOTEX v. CELGENE
`IPR2023-00512
`
`

`

`
`
`TABLE OF CONTENTS
`
`INTRODUCTION ............................................................................................ 1
`I.
`II. QUALIFICATIONS AND EXPERIENCE...................................................... 1
`III. BASIS OF OPINIONS ..................................................................................... 2
`IV. THE DEVELOPMENT OF NON-ENTERIC COATED TABLETS
`COMPRISING A THERAPEUTICALLY EFFECTIVE AMOUNT OF 5-
`AZACYTIDINE ......................................................................................................... 2
`A. There Were Many Known Hurdles In Developing 5-Azacytidine As A
`Therapeutic. ............................................................................................................ 3
`B. We Began Work On An Oral Formulation of 5-Azacytidine Knowing The
`Significant Hurdles The Project Presented. ............................................................ 5
`C. We Proposed An Enterically Coated Oral Formulation Of 5-Azacytidine To
`Overcome 5-Azacytidine’s Known Issues.............................................................. 8
`D. We Serendipitously Discovered That Non-Enteric Coated 5-Azacytidine
`Tablets Were Therapeutically Effective ................................................................. 9
`E. Non-Enteric Coated Tablets of 5-Azacytidine Displayed Unexpected
`Pharmacokinetic Results .......................................................................................12
`V. AVAILABILITY FOR CROSS-EXAMINATION .......................................14
`VI. RIGHT TO SUPPLEMENT ...........................................................................15
`VII. JURAT ............................................................................................................16
`
`
`i
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`Etter Decl. IPR2023-00512
`
`I, Jeffrey B. Etter, Ph.D., declare as follows:
`
`I.
`
`INTRODUCTION
`
`1.
`
`I have been retained by counsel for Celgene Corporation (“Patent
`
`Owner”) in connection with Apotex Inc. v. Celgene Corporation, No.
`
`IPR2023-00512, challenging claims 1, 2, 6-9, 11-28, 32-36, and 38-43 of U.S.
`
`Patent No. 8,846,628 (“the ’628 patent”).
`
`2.
`
`I am a named inventor on ’628 patent, along with my former
`
`colleagues at Pharmion Dr. Mai Lai and Dr. Jay Thomas Backstrom.
`
`Ex.1001(’628 patent). I understand that Apotex Inc. (“Apotex”) has filed an Inter
`
`Partes Review (IPR) at the USPTO challenging claims 1, 2, 6-9, 11-28, 32-36, and
`
`38-43 of the ’628 patent. I have been asked to explain how I and my co-inventors
`
`developed the inventions described in the ’628 patent.
`
`3.
`
`I am being compensated for my time in connection with this matter at
`
`my standard consulting rate, which is $275.00 per hour. My compensation is not
`
`dependent in any way upon the substance of my testimony or the outcome of this
`
`matter.
`
`II. QUALIFICATIONS AND EXPERIENCE
`
`4.
`
`I earned my bachelor’s degree with a major in chemistry from
`
`Franklin & Marshall College in 1982. I earned my Ph.D. in organic chemistry
`
`from the University of Colorado in 1987.
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`Etter Decl. IPR2023-00512
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`5.
`
`Since earning my Ph.D., I have spent over 30 years in the drug
`
`development industry, holding positions as Director of Analytical Development at
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`Somatogen (1990-1998), VP of Manufacturing at RxKinetic (1998-2002), Director
`
`of Drug Product at Allos Therapeutics (2002-2004), Director of Drug Product at
`
`Pharmion (2005-2008), Director of Formulations at Celgene (2008-2009), and
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`Director, Senior Director, VP, and Senior VP of Pharmaceutical Development at
`
`Clovis Oncology (2009-2023). This year, I formed and am the managing member
`
`of Etter CMC Consulting, LLC where I consult for various clients on the
`
`production and development of drug products.
`
`6. My curriculum vitae, which lists my professional experience and
`
`qualifications in greater detail, is attached hereto as Appendix A.
`
`III. BASIS OF OPINIONS
`
`7.
`
`I have considered the materials listed in Appendix B.
`
`IV. THE DEVELOPMENT OF NON-ENTERIC COATED TABLETS
`
`COMPRISING A THERAPEUTICALLY EFFECTIVE AMOUNT OF
`
`5-AZACYTIDINE
`
`8.
`
`I was hired by Pharmion in 2004 to develop an oral formulation of 5-
`
`azacytidine to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia
`
`(AML or acute myelogenous leukemia). I worked closely with Dr. Mei Lai to
`
`develop oral formulations of 5-azacytidine, while Dr. Backstrom spearheaded the
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`Etter Decl. IPR2023-00512
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`clinical trials. Our work resulted in the inventions described in the ’628 patent and
`
`the FDA-approved drug Onureg®. I describe our work in more detail as follows.
`
`A.
`
`There Were Many Known Hurdles In Developing 5-Azacytidine
`As A Therapeutic.
`
`9.
`
`In taking on the project of developing an oral formulation of 5-
`
`azacytidine, I was well aware of the known hurdles identified in the literature
`
`through decades of others trying to formulate 5-azacytidine.
`
`10.
`
`5-azacytidine is a nucleoside similar to the common nucleoside,
`
`cytidine. Ex.1001(’628 patent), 2:37-62. 5-azacytidine has a nitrogen atom in
`
`place of a carbon atom present in cytidine, which is highlighted in the structure
`
`below (Ex.1001(’628 patent), 2:48-62):
`
`
`
`11.
`
`5-azacytidine was well-known as a promising anti-tumor drug since
`
`the 1960s. See, e.g., Ex.2012(Čihák), 2091, 2100 (noting the compound’s
`
`“pronounced… cancerostatic effects). After administration of 5-azacytidine,
`
`cancer cells will incorporate the nucleoside into DNA and RNA. Id., 3:9-27.
`
`Upon incorporation, 5-azacytidine “restor[es] normal functions” by promoting “re-
`
`
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`3
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`expression of genes involved in normal cell cycle regulation, differentiation and
`
`death” leading to “the death of rapidly dividing cells, including cancer cells….”
`
`Etter Decl. IPR2023-00512
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`Id., 3:9-22.
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`12. Despite its promise as an anti-cancer drug, there were well-known
`
`problems of using 5-azacytidine as a therapeutic. In fact, Dr. Ladislav Hanka, who
`
`first purified 5-azacytidine, informed me of his difficulty in isolating 5-azacytidine
`
`due to its instability. See also Ex.2021(Lin), 1229 (recognizing that a “major
`
`problem encountered in the clinical formulation of 5-azacytidine is its chemical
`
`instability”).
`
`13. One reason 5-azacytidine is unstable is that it breaks down in aqueous
`
`solutions via a process called hydrolysis. See Ex.1014(Chan), 807 (5-azacytidine’s
`
`“[i]nstab[ility] in aqueous solution” “ha[d] long been known.”);
`
`Ex.2003(Aparicio), 631 (concluding that “azacytidine… ha[s] not been
`
`dramatically successful [as a therapeutic], and pose[s] significant restrictions on
`
`dosing schedule adjustments because of [its] instability in aqueous solution and
`
`[its] side effects”).
`
`14. Another reason 5-azacytidine is unstable is that an enzyme, cytidine
`
`deaminase, rapidly breaks down 5-azacytidine. See Ex.2009(Chabner), 2763, 2765
`
`(noting that enzymatic degradation “may compromise the effectiveness of 5-
`
`azacytidine in treating human leukemia”).
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`Etter Decl. IPR2023-00512
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`15. Despite decades of research by several different entities, only one
`
`company, Pharmion, had successfully brought a 5-azacytidine product to market.
`
`In March 2004, Pharmion received FDA approval for the first 5-azacytidine
`
`formulation named Vidaza®, an injectable formulation for treating MDS.
`
`Ex.1007(Vidaza® Label 2004), 0008, 0023-0024; see also Ex.1008(Vidaza®
`
`Label 2007), 0008, 0011; Ex.2018(Kaminskas), 176.
`
`16. The formulation and administration of Vidaza® were consistent with
`
`the known issues of 5-azacytidine as a treatment. Literature reported that 5-
`
`azacytidine needed to be “given immediately” intravenously after dissolution in
`
`water due to 5-azacytidine’s instability. Ex.2031(Weiss), 413-414, 418; see
`
`Ex.2090(Karon); Ex.2128(Von Hoff); Ex.2100(McCredie); Ex.2126(VoglerI);
`
`Ex.2127(VoglerII). Vidaza® is a lyophilized formulation that requires
`
`administration of the formulation shortly after reconstitution in water so a
`
`therapeutic pharmacokinetic profile is achieved before metabolism, hydrolysis, and
`
`degradation eliminate the drug. See Ex.1007-0008, -0023-0024(Vidaza® Label
`
`2004); Ex.1008-0008, -0011(Vidaza® Label 2004).
`
`B. We Began Work On An Oral Formulation of 5-Azacytidine
`Knowing The Significant Hurdles The Project Presented.
`
`17.
`
`I started at Pharmion shortly after the approval of Vidaza® and was
`
`specifically tasked with developing an oral formulation of 5-azacytidine.
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`Etter Decl. IPR2023-00512
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`18. We were interested in developing an oral formulation because as an
`
`injectable formulation, Vidaza® presented challenges in administration and patient
`
`comfort. Administration of Vidaza® required patients to receive the injection for
`
`seven consecutive days every four weeks. Ex.1007-0022(Vidaza® Label 2004);
`
`Ex.1008-0011(Vidaza® Label 2007). Many patients reported injection-site
`
`reactions including discomfort. Ex.1007-0018-0021(Vidaza® Label 2004);
`
`Ex.1008-0010(Vidaza® Label 2007). In comparison, if it could be achieved an
`
`oral formulation could provide a more convenient treatment with less
`
`complications. See Ex.1001(’628 patent), 3:50-54 (explaining that an oral
`
`administration “would be more desirable and convenient for patients and doctors,”
`
`“eliminat[e] injection-site reactions that may occur with SC [subcutaneous]
`
`administration,” and “permit[] improved patient compliance.”); see also
`
`Ex.2076(Curtiss), 575 (disclosing that oral dosage forms have potential benefits
`
`over injectable forms including “ease of administration, patient preference, and
`
`lower risk of complications”).
`
`19.
`
` Despite the benefits that an oral formulation could provide, I was
`
`keenly aware that nobody had been successful in developing one and of the issues
`
`of hydrolysis and enzymatic degradation facing 5-azacytidine formulations. I
`
`knew of the work of several research groups that had attempted to develop an oral
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`6
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`Etter Decl. IPR2023-00512
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`formulation. None had been able to develop an oral formulation that was
`
`therapeutically effective.
`
`20. For example, in the 1970s researchers reported that providing oral
`
`intubation of 5-azacytidine resulted in “much lower” 5-azacytidine blood levels
`
`compared to injectable formulations. Ex.2101(Neil), 463, 464. Researchers in
`
`1985 reported that in administering 5-azacytidine orally to baboons, “only a
`
`fraction of the administered amount [wa]s available,” possibly because 5-
`
`azacytidine “is rapidly deaminated … by cytidine deaminase, which is widely
`
`distributed in various tissues” including “the gastrointestinal mucosa….”
`
`Ex.2077(DeSimone), 285, 283-284; see also Ex.1031(Dover), Abstract, 528
`
`(reporting no effect when oral 5-azacytidine was given alone, instead only seeing
`
`an increase in F reticulocyte production if given with tetrahydrouridine). Even
`
`when formulated to overcome deamination, such as by administering 5-azacytidine
`
`with a cytidine deaminase inhibitor, researchers determined that oral 5-azacytidine
`
`“was ineffective.” Ex.2079(Dunbar), 467. Along with the rest of the field, we
`
`understood that that “oral delivery of members of this class of compounds [of
`
`deoxycytidine and cytidine analogs] has proven difficult due to combinations of
`
`chemical instability, enzymatic instability, and/or poor tissue permeability.”
`
`Ex.2123(60/824,320), ¶[0007].
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`7
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`Etter Decl. IPR2023-00512
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`21. Given these well-documented issues and the failure of anyone to
`
`develop an oral formulation of 5-azacytidine, I had no expectation that we would
`
`be successful in our own efforts.
`
`C. We Proposed An Enterically Coated Oral Formulation Of 5-
`Azacytidine To Overcome 5-Azacytidine’s Known Issues
`
`22. Starting around 2005, I began work to develop oral formulations of 5-
`
`azacytidine. I first conducted studies to determine in what part of the body 5-
`
`azacytidine would be best absorbed.
`
`23. Specifically, I conducted a study using an ex vivo intestinal cell
`
`model, which suggested that 5-azacytidine is best absorbed through the colon. See
`
`e.g., Ex.2123(60/824,320), ¶¶ [00105]-[00108]; Ex.2041(WO2008/028193),
`
`¶¶[00120]-[00128]. Based on this and the well-documented issues with 5-
`
`azacytidine, I concluded that 5-azacytidine should be formulated “to avoid the
`
`chemical and enzymatic degradation occurring presystemically.” (Ex.1034(Stoltz).
`
`24.
`
`I proposed that we develop a formulation of 5-azacytidine using an
`
`enteric coating so that the drug would release in the colon. I also believed that
`
`given the well-documented issues with 5-azacytidine degradation, an enterically-
`
`coated formulation might protect the drug from degradation in the stomach and
`
`upper gastrointestinal tract. Ex.2123(60/824,320), ¶¶[0022]-[0023], [00114];
`
`Ex.2041(WO2008/028193), ¶¶[0024]-[0025], [00134]; Ex.1022, 2085-2094(Beach
`
`Decl.) (explaining that Pharmion “focused on [5-azacytidine formulations] that
`
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`Etter Decl. IPR2023-00512
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`were protected from the acidic environment of the stomach, e.g., those requiring
`
`enteric coating[s],” consistent with the understanding in the field at the time); see
`
`also Ex.1001(’628 patent), 3:58-65. In other words, we believed that by delaying
`
`the release of 5-azacytidine beyond the stomach, i.e., using an enteric coated
`
`formulation, we might improve oral bioavailability to target the colon through
`
`better tissue absorption and minimization of acid-dependent hydrolytic
`
`degradation. Ex.2123(60/824,320), ¶[0023]; see also ¶[00114].
`
`25. We proposed and tested a number of enterically-coated formulations,
`
`and this work is described in U.S. Provisional Patent Application 60/824,320 and
`
`subsequent U.S. and international patent applications. See Ex.2123(60/824,320);
`
`Ex.2124(US2008/0057086), ¶¶[0132], [0137], [0174]; Ex.2041(WO2008/028193).
`
`D. We Serendipitously Discovered That Non-Enteric Coated 5-
`Azacytidine Tablets Were Therapeutically Effective
`
`26. Using an enterically-coated formulation of 5-azacytidine, we
`
`conducted a small-scale pilot study which showed absorption following oral
`
`administration.
`
`27. Following up on these results, we performed additional tests using a
`
`second batch of enteric-coated tablets. See Ex.1001(’628 patent), Tables 4, 5, 7
`
`(disclosing enteric-coated “Formulation 2”). Unlike our initial study, this second
`
`batch of enteric-coated tablets resulted in minimal absorption of 5-azacytidine.
`
`Repeating these tests with additional batches of enteric-coated 5-azacytidine
`
`
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`9
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`Etter Decl. IPR2023-00512
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`(“Formulation 4” and “Formulation 5”) also did not demonstrate significant
`
`absorption by patients. See e.g., Ex.1050(61/157,875), Figs. 10-15, ¶¶[0039]-
`
`[0044], Tables 2-3, 5, ¶¶[00187], [00189]-[00193]; Ex.1051(’145 provisional),
`
`Tables 2-3; Ex.1001(’628 patent), Figs. 10-15, 9:6-25, Tables 3-5, 7, 73:1-74:16.
`
`28.
`
`In problem-solving these inconsistent results, Dr. Lai and I looked
`
`back at the tablet compositions used in our first pilot study and discovered that the
`
`tablet formulation was manufactured incorrectly. Despite our instructions for the
`
`tablet to be enterically coated, we later learned that “Formulation 1” had a “leaky”
`
`enteric coating. Ex.1001(’628 patent), 64:19-21.
`
`29. These results caused us to consider new ways of administering 5-
`
`azacytidine. Using what we learned from the pilot study, we hypothesized that 5-
`
`azacytidine could be administered in a therapeutically effective amount using a
`
`non-enteric coated tablet formulation. We therefore abandoned our research into
`
`enteric-coated tablets and took our research in a new direction. This new approach
`
`was contrary to our prior understanding, based on the decades of literature, that 5-
`
`azacytidine was chemically and enzymatically unstable such that it should not be
`
`released in the stomach or upper gastrointestinal tract.
`
`30. We then engaged in extensive research to test our new hypothesis.,
`
`We developed several different non-enteric coated tablets of 5-azacytidine “which
`
`did not undergo the enteric film-coating step” (i.e., the non-enteric coated
`
`
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`10
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`Etter Decl. IPR2023-00512
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`“Formulation 3” and “Formulation 6”). Ex.1051(’145 provisional), ¶[0056],
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`Figure 1. These non-enterically coated tablet formulations of 5-azacytidine are
`
`described in the ’628 patent. Ex.1001(’628 patent), Tables 3-5, 7, 64:29-50, Fig. 1.
`
`31. Using the non-enterically coated tablet formulations of the ’628
`
`patent, we demonstrated for the first time that non-enteric, “immediate release
`
`azacitidine formulations provide a superior percent exposure… than enteric-coated
`
`azacitidine formulations.” Ex.1001(’628 patent), 73:3-6; see also id., 74:14-16;
`
`Ex.1051(’145 provisional), ¶[0070]. Specifically, we observed positive clinical
`
`activity in patients following administration of the non-enteric coated tablet
`
`formulation of 5-azacytidine. See e.g., Ex.1001(’628 patent), 68:48-71:44; see
`
`also Ex.1050(’875 provisional), ¶[0174]-[0183]. Thus, contrary to the known
`
`chemical and enzymatic instability of 5-azacytidine, we made the surprising and
`
`unexpected “discovery that 5-azacytidine… [is] best absorbed and most
`
`efficaciously delivered if instantly released, upon oral administration, in the upper
`
`gastrointestinal tract, e.g., the stomach.” Ex.1051-0018(’145 provisional), ¶[0022].
`
`32.
`
`In sum, and as described in the ’628 patent, we demonstrated for the
`
`first time that a non-enteric coated oral tablet formulation of 5-azacytidine was
`
`therapeutically effective in treating AML or MDS. As we described in the ’628
`
`patent, these non-enteric coated formulations “demonstrated bioavailability in
`
`patients” with “positive clinical activity [for] patients” and had superior exposure
`
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`11
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`Etter Decl. IPR2023-00512
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`compared to enterically coated formulations despite 5-azacytidine being released in
`
`the harsh gastric environment. Id., 71:39-44, 73:1-6. We made this discovery
`
`serendipitously, running counter to over forty years of scientific research.
`
`E. Non-Enteric Coated Tablets of 5-Azacytidine Displayed
`Unexpected Pharmacokinetic Results
`
`33.
`
`I was surprised by the results of my team’s fortuitous discovery that
`
`not only did a non-enterically coated tablet of 5-azacytidine provide a
`
`therapeutically effective amount, but it also provided a much higher amount than
`
`the analogous enterically coated formulations and provided strong efficacy as
`
`compared to a subcutaneous dose. Our studies showed that non-enteric coated
`
`tablets of 5-azacytidine demonstrated superior pharmacokinetic values as
`
`compared to enteric coated tablets.
`
`34. For example, the patent describes that non-enteric coated tablets
`
`achieve higher maximum plasma concentration values. Figure 13, annotated and
`
`reproduced below, demonstrates that the non-enteric coated tablet, labeled
`
`“Formulation 3” or “F3,” had a higher maximum plasma concentration than that of
`
`the enteric coated “Formulation 4” or “F4”.
`
`
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`12
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`Etter Decl. IPR2023-00512
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`
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`Ex.1001(’628 patent), Fig. 13; see also id., Fig. 10, -0063, Table 7. Likewise, the
`
`’628 patent describes the non-enteric coated tablets provided shorter times to
`
`maximum plasma concentration (id., Fig. 10, Fig. 16, 72:39-52, 72:44-58, 73:22-
`
`32, 74:18-23), greater area-under-the-curve values (id., Fig. 12, 72:39-52, 72:44-
`
`58, 73:1-8, 74:4-16), and larger relative bioavailabilities (id., Fig. 14, Fig. 15,
`
`73:59-74:16) than corresponding enteric formulations.
`
`35.
`
`In addition, our studies showed that the lower drug exposure of non-
`
`enterically coated oral 5-azacytidine provided surprisingly effective clinical results
`
`compared to higher levels achieved by traditional intravenous administration. In
`
`our studies, non-enteric tablets comprising 360 mg of 5-azacytidine or less
`
`achieved bioavailability of between 11% and 21% of that achieved with traditional
`
`
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`13
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`Etter Decl. IPR2023-00512
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`subcutaneously administered 5-azacytidine. See Ex.1001(’628 patent), 73:64-74:3,
`
`Fig. 12, Fig. 14. Even though only a fraction of the 5-azacytidine was
`
`bioavailable, this low amount was surprisingly effective. For instance, non-
`
`enterically coated tablets containing either 240 mg or 300 mg of 5-azacytidine
`
`were provided to several patients diagnosed with MDS. See Ex.1001(’628 patent),
`
`66:50-67, Table 8. Not only did these non-enteric coated tablets “permit the
`
`delivery of azacitidine at lower doses over a more prolonged period of time,” but
`
`several of the patients exhibited notable improvements in their conditions
`
`following receipt of these lower doses released in the stomach. Ex.1001(’628
`
`patent), 71:9-18. I understand from discussions with Dr. Jay Backstrom and his
`
`team at the time that two of the patients receiving these non-enteric coated tablets
`
`exhibited major hematologic improvements, two patients exhibited complete
`
`morphological responses, and two patients exhibited extended complete marrow
`
`responses. Ex.1001(’628 patent), Table 10. Thus, we surprisingly discovered oral
`
`5-azacytidine’s ability to achieve positive clinical outcomes in patients despite a
`
`lower exposure to the drug than with subcutaneous doses. See, e.g., Ex.1022,
`
`2085-2094(Beach Decl.), 2093.
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`V. AVAILABILITY FOR CROSS-EXAMINATION
`
`36.
`
`In signing this declaration, I recognize that the declaration will be
`
`filed as evidence in a contested case before the Patent Trial and Appeal Board of
`
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`14
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`Etter Decl. IPR2023-00512
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`the United States Patent and Trademark Office. I also recognize that I may be
`
`subject to cross examination in the case and that cross examination will take place
`
`within the United States. If cross examination is required of me, I will appear for
`
`cross examination within the United States during the time allotted for cross
`
`examination.
`
`VI. RIGHT TO SUPPLEMENT
`
`37.
`
`I reserve the right to supplement my opinions in the future to respond
`
`to any arguments that Petitioner raises and to take into account new information as
`
`it becomes available to me.
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`15
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`Etter Deel. IPR2023-005 l 2
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`VII. JURAT
`
`3 8.
`
`I declare that all statements made herein of my own knowledge are
`
`true and that al] statements made on information and belief are believed to be true;
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`and further that these statements were made with the knowledge that willful false
`
`statements and the like so made are punishable by fine or imprisonment, or both,
`
`under Section 1001 of Title 18 of the United States Code.
`
`Dr. effrey B. Etter
`
`Date:
`
`/) Oc} .2DE
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`16
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`APPENDIX A
`APPENDIX A
`
`17
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`17
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`

`

`Jeffrey B. Etter, Ph.D.
`
`Jeffrey B. Etter, Ph.D.
`Curriculum Vitae
`
`SUMMARY:
`Over 35 years of experience in the biotechnology/pharmaceutical industry in the areas of
`formulation development, analytical method development, manufacturing, and drug
`delivery of traditional and nuclear medicinal products. Extensive experience with project
`and personnel management, method and process validation, quality programs and
`regulatory requirements/submissions.
`
`RESEARCH AND WORK EXPERIENCE:
`
`ETTER CMC CONSULTING, LLC, BOULDER, CO
`8/23 – Present Managing Member
` Consulting to support drug substance and drug product development and
`manufacturing for clinical studies and commercial products
`
`CLOVIS ONCOLOGY CORPORATION, BOULDER, CO
`9/16 – 7/23
`Senior Vice President Pharmaceutical Development
`2/13 - 9/16
`Vice President Pharmaceutical Development
`3/10 – 2/13
`Senior Director Pharmaceutical Development
`7/09 – 2/10
`Director of Pharmaceutical Development
`Direction of process and analytical development at contract manufacturing and
`research organizations to produce both clinical and commercial drug substances.
`Direction of process, formulation, and analytical development at contract
`manufacturing and research organizations to produce oncology non-nuclear and
`nuclear drug products.
`Responsibilities: Establishment and direction of strategic drug substance and drug
`product development and manufacturing programs. Identification and coordination
`of development, manufacturing, and testing facilities to execute those programs.
`Troubleshooting of manufacturing, formulation and analytical method issues for
`drug substance and drug product. Preparation and maintenance of division budgets.
`Coordination of Technical Operations, Validation, Manufacturing, Supply Chain
`Operations with Quality Assurance, Regulatory Affairs, Clinical Operations, and
`Commercial group activities. Review and approval of CMC sections for regulatory
`submissions. Interaction with Health Authorities on CMC related issues. Technical
`review of drug in-licensing opportunities.
`
`PHARMION CORPORATION, BOULDER, CO
`7/04 – 7/09
`Director of Formulation Development
`(As of March 2007, Pharmion was purchased by Celgene Corp)
`Direction of formulation development, contract manufacturing, and research
`organizations relative to oncology drug products.
`Responsibilities: Development of drug product formulation programs.
`Identification and coordination of testing facilities to execute those formulation
`programs. Troubleshooting of manufacturing, formulation and analytical method
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`Jeffrey B. Etter, Ph.D.
`
`issues for drug product. Compilation of drug product sections for regulatory
`submissions. Technical review of drug in-licensing opportunities.
`
`ALLOS THERAPEUTICS, INC.., WESTMINSTER, CO
`9/02 – 7/04
`Director of Drug Products
`Direction of contract manufacturing and research organizations relative to oncology
`drug products.
`Responsibilities: Simultaneous management of multiple contract drug product
`manufacturers. Establishment and monitoring of drug product stability studies.
`Trouble shooting formulation and analytical method issues for drug product.
`Compilation of drug product sections for regulatory submissions.
`
`RXKINETIX INC., LOUISVILLE, CO
`9/98 – 9/02
`Vice President of Manufacturing
`Direction of Manufacturing, Process Development, Formulation Development and
`Analytical Development for the production of innovative drug delivery products.
`Target drugs include proteins, peptides, genetic materials and small molecules.
`Responsibilities: Develop research programs and establish standard operating
`procedures for formulation, analytical and production processes, coordination of
`collaborations with external clients, selection and management of contract
`manufacturing of clinical trial materials, submission of patent disclosures, and
`maintenance of division budgets and grants.
`
`SOMATOGEN INC. (BAXTER HEALTHCARE), BOULDER, CO
`2/97-9/98
`Director of Analytical Development
`(As of May 1998, Somatogen was purchased by Baxter Healthcare)
`Management of all analytical development activities including Analytical
`Chemistry, Protein Chemistry, Immunoassay and Analytical Services laboratories
`in support of process validation and cGMP manufacturing operations.
`Responsibilities: Direction of research, preparation of regulatory submissions,
`interaction and coordination with internal and external groups to ensure target
`production times, and development and maintenance of division budgets.
`
`Staff Scientist (Grades II through Senior)
`8/93-1/97
`Direction of three research associates and of Analytical Services lab containing five
`technicians and one supervisor.
`Responsibilities: Development, validation and technology transfer of analytical
`methods to be employed for in-process analysis, bulk product and final product
`release of recombinant human hemoglobin. Coordinated resources for process
`troubleshooting. Assistance in the preparation of regulatory submissions.
`
`Manager Quality Control
`7/92-7/93
`Direction of a staff of two supervisors and twenty analysts covering chemical and
`microbiological analysis for manufacturing of recombinant human hemoglobin.
`Compliance with cGMP FDA regulations. Establishment of IQA program for
`process raw materials. Coordination with departmental heads for analytical
`services. Development and implementation of LIMS system.
`
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`Jeffrey B. Etter, Ph.D.
`
`Supervisor Quality Control
`1/91-6/92
`Development and validation of new analytical techniques. Compliance with cGMP
`FDA regulations. Assisted in the development of purification-isolation and final
`fill-finish strategies of product.
`
`Process Development Scientist
`7/90-12/90
`Evaluation of physical characteristics of produced protein. Design and evaluation
`of drug formulations for improved stability.
`
`BIOSTAR MEDICAL PRODUCTS INC., BOULDER, CO
`6/88-6/90
`Research Scientist
`Research and development of novel techniques for covalent coupling biologically
`reactive proteins to continuous silicon surfaces for immunoassay production.
`
`EDUCATION:
`1987-1988
`
`Postdoctoral Research Associate with Professor Barry M. Trost at Stanford
`University, Stanford, CA.
`
`1982-1987
`
`Ph.D. in Organic Chemistry with Professor Gary A. Molander at the
`University of Colorado, Boulder, CO.
`
`1978-1982
`
`A.B. in chemistry at Franklin and Marshall College, Lancaster, PA.
`
`AWARDS AND HONORS:
`1987-1988
`National Institute of Health Postdoctoral Fellowship, Stanford
`University, Stanford, CA.
`
`1985-1986
`
`University of Colorado Fellowship, University of Colorado, Boulder,
`CO.
`
`1983
`
`John S. Meek Teaching Award, University of Colorado, Boulder, CO.
`
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`US PATENTS:
`
`Jeffrey B. Etter, Ph.D.
`
`Oral Formulations of Cytidine Analogs and Methods of Use Thereof. Etter, J.B.;
`Lai, M.; Backstrom, J.T., U.S. Patent Number 11,571,436, February 7, 2023
`
`Isotopologues of 5-Azacitidine. Traverse, J.F.; Leong, W.W.; Etter, J.B.; Lai, M.;
`Backstrom, J.T., U.S. Patent Number 10,646,5033; May 12, 2020.
`
`Isotopologues of 5-Azacitidine. Traverse, J.F.; Leong, W.W.; Etter, J.B.; Lai, M.;
`Backstrom, J.T., U.S. Patent Number 10,463,683; November 5, 2019.
`
`Isotopologues of 5-Azacitidine. Traverse, J.F.; Leong, W.W.; Etter, J.B.; Lai, M.;
`Backstrom, J.T., U.S. Patent Number 10,220,050; March 5, 2019.
`
`High Dosage Strength Tablets of Rucaparib; Etter, J., US Patent Number
`10,130,636, November 20, 2018
`
`High Dosage Strength Tablets of Rucaparib; Etter, J., US Patent Number
`9,987,285, June 5, 2018
`
`Pharmaceutical Compositions of Cytidine Analogs and Method of Use Thereof.
`Tutino, A.; Lai, M.; Etter, J.B., U.S. Patent Number 9,393,255, July 19, 2016
`
`Oral Formulations of Cytidine Analogs and Methods of Use Thereof. Etter, J.B.;
`Lai, M.; Backstrom, J.T., U.S. Patent Number 8,846,628, September 30, 2014
`
`High-Concentration Protein Formulations and Method of Manufacture. Carpenter,
`J.F.; Etter, J.B.; Samaniego, A.C. U.S. Patent Number 8,372,798, February 12,
`2013
`
`Composition of Allosteric Hemoglobin Modifiers and Methods of Making the
`Same. Quick, A.; Santos, A.M.; Carvalho, A.J.G.G.; Johnson, D.G; Etter, J.B.;
`Murray, C. U.S. Patent Number 7,847,120, December 7, 2010.
`
`Flow-through Optical Assay Devices Providing Laminar Flow if Fluid Samples,
`and Methods of Construction Thereof. Drews, J.A.; Bogart, G.R.; Etter, J.B.;
`Steaffens, J.W.; Ostroff, R.M.; Crosby, M., U.S. Patent Number 7,153,651
`December 26, 2006.
`
`Particulate Drug-Containing Products and Method of Manufacture. Etter, J.B. U.S.
`Patent Number 7,125,566, October 24, 2006.
`
`Device for Mass Transport Assisted Optical Assays. Drewes, J.A.; Bogart, G.R.;
`Etter, J.B.; Steafens, J.W.; Ostroff, R.M.; Crosby, M. U.S. Patent Number
`6,933,112, August 23, 2005.
`
`Composition for Delivery of Hematopoetic Growth Factor. Rosenthal, G.J.; Etter,
`J.B. U.S. Patent Number 6,875,441, April 5, 2005.
`
`Particulate Insulin-Containing Products and Method of Manufacture. Etter, J.B.
`U.S. Patent Number 6,761,909, July 13, 2004.
`
`Treatment of Mucositis. Rosenthal, G.J.; Etter, J.B.; Rodell, T.C.; Scahuer, W.H.;
`Samaniego, A. U.S. Patent Number 6,685,917, February 3, 2004.
`
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`Jeffrey B. Etter, Ph.D.
`
`Particulate Drug-Containing Products and Method of Manuf