UNITED STATES PATENT AND TRADEMARK OFFICE
`
`__________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`__________
`
`
`REGENERON PHARMACEUTICALS, INC.,
`Petitioner
`
`v.
`
`NOVARTIS PHARMA AG,
`NOVARTIS TECHNOLOGY LLC,
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owner
`
`__________
`
`
`Case IPR2021-00816
`Patent 9,220,631
`
`__________
`
`
`DECLARATION OF JUERGEN SIGG, PH.D., IN SUPPORT OF
`NOVARTIS’S
`PATENT OWNER RESPONSE
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`
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`Novartis Exhibit 2206.001
`Regeneron v. Novartis, IPR2021-00816
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`
`
`__________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`__________
`
`
`REGENERON PHARMACEUTICALS, INC.,
`Petitioner
`
`v.
`
`NOVARTIS PHARMA AG,
`NOVARTIS TECHNOLOGY LLC,
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owner
`
`__________
`
`
`Case IPR2021-00816
`Patent 9,220,631
`
`__________
`
`
`DECLARATION OF JUERGEN SIGG, PH.D., IN SUPPORT OF
`NOVARTIS’S
`PATENT OWNER RESPONSE
`
`
`
`
`
`
`Novartis Exhibit 2206.001
`Regeneron v. Novartis, IPR2021-00816
`
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`TABLE OF CONTENTS
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`INTRODUCTION .......................................................................................... 2
` I.
`II. GENENTECH TRIED TO DEVELOP A TERMINALLY
`STERILIZED PFS FOR INTRAVITREAL INJECTION OF A VEGF
`ANTAGONIST BUT FAILED ...................................................................... 2
`III. SILICONE OIL LEVELS IN COMMERCIALLY AVAILABLE
`SYRINGES ..................................................................................................... 7
`IV. VETTER’S SKEPTICISM THAT A PFS COULD FUNCTION
`PROPERLY WITH LESS THAN 100 µG OF SILICONE OIL ................... 9
`V. NOVARTIS WAS NOT ABLE TO TERMINALLY STERILIZE
`THE LUCENTIS PFS WITH THE PROCESS DESCRIBED IN WO
`’877 ............................................................................................................... 11
`VI. NOVARTIS REDESIGNED IMPORTANT ASPECTS OF THE
`SYRINGE AFTER FILING WO ’877 BUT BEFORE
`COMPLETING DEVELOPMENT OF THE LUCENTIS PFS ................... 14
`VII. TESTING OF LUCENTIS PFS ................................................................... 16
`VIII. GENENTECH LICENSE ............................................................................. 18
`IX. DECLARATION .......................................................................................... 20
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`1
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`Novartis Exhibit 2206.002
`Regeneron v. Novartis, IPR2021-00816
`
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`
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`I, Juergen Sigg, declare and state as follows:
`I.
`INTRODUCTION
`1.
`I am an Executive Director of Science and Technology in Biologics
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`Drug Product Development at Novartis Pharma AG (“Novartis”). As part of my
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`duties at Novartis, I serve as the lead scientist for formulation and process
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`development of assigned biologic drug products.
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`2.
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`I have a degree in pharmaceutical science and a Ph.D. in
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`pharmaceutical technology. Over the course of my career at Novartis, I have been
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`the lead formulation and process development scientist on several prefilled syringe
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`(“PFS”) products. My work in this area began in 1995, and continues to this day.
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`Several of the PFS products I worked on, including Xolair® and Extavia®, made it
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`to the market. Relevant here, I served as the technical lead in the development of
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`the Lucentis® PFS.
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`3.
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`I am a named inventor on several patents and patent applications,
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`including U.S. Patent No. 9,220,631 (“’631 patent”) and the abandoned patent
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`application WO 2011/006877 (“WO ’877”).
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`4.
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`I have personal knowledge of the facts set forth below.
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`II. GENENTECH TRIED TO DEVELOP A TERMINALLY
`STERILIZED PFS FOR INTRAVITREAL INJECTION OF A VEGF
`ANTAGONIST BUT FAILED
`5.
`Lucentis is the brand name for a compound discovered by Genentech
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`called ranibizumab. Ranibizumab functions as a VEGF antagonist and is used to
`2
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`Novartis Exhibit 2206.003
`Regeneron v. Novartis, IPR2021-00816
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`treat degenerative eye diseases. Lucentis is administered through intravitreal
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`injection into the eye.
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`6.
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`Novartis Exhibit 2206.004
`Regeneron v. Novartis, IPR2021-00816
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`Novartis Exhibit 2206.005
`Regeneron v. Novartis, IPR202 1-008 16
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`10.
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`———oS
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`11.
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`12.
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`Novartis Exhibit 2206.005
`Regeneron v. Novartis, IPR2021-00816
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`13.
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`——>we
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`Novartis Exhibit 2206.006
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.006
`Regeneron v. Novartis, IPR2021-00816
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`16.
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`I have reviewed WO 2008/077155 (“Lam”), Ex. 1029. Xanthe Lam,
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`the first named inventor on the patent application,
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`17.
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`Novartis Exhibit 2206.007
`Regeneron v. Novartis, IPR2021-00816
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`III. SILICONE OIL LEVELS IN COMMERCIALLY AVAILABLE
`SYRINGES
`19.
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` Novartis embarked on a
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`project to design its own novel PFS. I was appointed pharmaceutical development
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`lead of this project in late 2008. One of the design elements I focused on was the
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`amount of silicone oil in the syringe. A PFS requires lubrication, usually
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`pharmaceutical grade silicone oil, in order to function properly because of the
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`friction between the syringe’s glass barrel and its plunger. If there is too little
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`silicone oil, and therefore too much friction, it will take excessive force to move
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`7
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`Novartis Exhibit 2206.008
`Regeneron v. Novartis, IPR2021-00816
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`the plunger, resulting in difficulty to the physician in administering the injection
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`and possible damage to the patient’s eye during injection.
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`20.
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`Novartis Exhibit 2206.009
`Regeneron v. Novartis, IPR2021-00816
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`22.
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`IV. VETTER’S SKEPTICISM THAT A PFS COULD FUNCTION
`PROPERLY WITH LESS THAN 100 µg OF SILICONE OIL
`23.
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`25.
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`Novartis Exhibit 2206.0010
`Regeneron v. Novartis, IPR2021-00816
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`26.
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`NNNoo_D
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`Novartis Exhibit 2206.0011
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.0011
`Regeneron v. Novartis, IPR2021-00816
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`V. NOVARTIS WAS NOT ABLE TO TERMINALLY STERILIZE THE
`LUCENTIS PFS WITH THE PROCESS DESCRIBED IN WO ’877
`30.
`In addition to having low silicone oil levels, we also intended the
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`Lucentis PFS to be terminally sterilized, which, in the case of a syringe like the
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`Lucentis PFS, refers to sterilizing the outer surface of the PFS in its final protective
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`packaging.
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`31.
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`11
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`Novartis Exhibit 2206.0012
`Regeneron v. Novartis, IPR2021-00816
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`32.
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`33.
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`-1o*)OoGoGoGo
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`34.
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`12
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`Novartis Exhibit 2206.0013
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.0013
`Regeneron v. Novartis, IPR2021-00816
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`37.
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`38.
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`39.
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`40. Ex. 1007 is a copy of patent application WO ’877.
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`13
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`Novartis Exhibit 2206.0014
`Regeneron v. Novartis, IPR2021-00816
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`.
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`VI. NOVARTIS REDESIGNED IMPORTANT ASPECTS OF THE
`SYRINGE AFTER FILING WO ’877 BUT BEFORE COMPLETING
`DEVELOPMENT OF THE LUCENTIS PFS
`41. During Novartis’s development of the Lucentis PFS, we determined
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`14
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`42.
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`43.
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`(
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`Novartis Exhibit 2206.0015
`Regeneron v. Novartis, IPR2021-00816
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`44.
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`EN£mn-
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`45.
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`46.
`BROn
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`15
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`Novartis Exhibit 2206.0016
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.0016
`Regeneron v. Novartis, IPR2021-00816
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`47.
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`48.
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`VII. TESTING OF LUCENTIS PFS
`49.
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`50.
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`Novartis Exhibit 2206.0017
`Regeneron v. Novartis, IPR2021-00816
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`51.
`—
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`17
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`Novartis Exhibit 2206.0018
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.0018
`Regeneron v. Novartis, IPR2021-00816
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`VIII. GENENTECH LICENSE
`52.
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`53.
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`18
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`Novartis Exhibit 2206.0019
`Regeneron v. Novartis, IPR2021-00816
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`19
`19
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`Novartis Exhibit 2206.0020
`Regeneron v. Novartis, IPR202 1-008 16
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`Novartis Exhibit 2206.0020
`Regeneron v. Novartis, IPR2021-00816
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`
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`IX. DECLARATION
`
`54.
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`I hereby declare that all statements made herein of my own
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`knowledge are true and that all statements made on information and belief are
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`believed to be true; and further that these statements were made with the
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`knowledge that willful false statements and the like so made are punishable by fine
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`or imprisonment, or both, under Section 1001 of Title 18 of the United States
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`Code.
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`Dated: January 18, 2022
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`Digitally signed by Sigg
`Juergen
`ON: dc=com, dc=novartls,
`ou"'"peoplo, ou~Go,
`serialNumber= 196126,
`
`S I• g g
`J uergen ~:~:;~~~~1.~;2,:0631
`By: /Juergen Sigg2 Ph.D./
`Juergen Sigg, Ph.D.
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`+01'00'
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`20
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`Novartis Exhibit 2206.0021
`Regeneron v. Novartis, IPR2021-00816
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`
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