Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 1 of 15 PageID #: 48163
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit 16
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit 16
`
`
`
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 2 of 15 PageID #: 48164
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF WEST VIRGINIA
`AT CLARKSBURG
`
`
`
`
`
`
`
`
`
`
`Plaintiff,
`
`
`v.
`
`
`REGENERON PHARMACEUTICALS, INC.,
`
`
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`
`
`
`
`
`Defendant.
`
`
`
`Case No. 1:22-cv-00061-TSK
`
`
`CONFIDENTIAL:
`CONTAINS ATTORNEY’S EYES
`ONLY INFORMATION
`
`
`SUPPLEMENTAL
`RESPONSIVE EXPERT REPORT OF GREGORY MACMICHAEL, PH.D.
`REGARDING THE NON-INFRINGEMENT OF CLAIM 18 OF
`U.S. PATENT NO. 11,084,865
`
`
`
`
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 3 of 15 PageID #: 48165
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION. ............................................................................................................. 1
`
`PROFESSIONAL QUALIFICATIONS AND BACKGROUND. ..................................... 2
`
`III.
`
`SUPPLEMENTAL ANALYSIS. ........................................................................................ 2
`
`A.
`
`B.
`
`CLAIM 18. ................................................................................................................ 2
`
`MYLAN’S M710 BLA PRODUCT DOES NOT INFRINGE CLAIM 18. ........................... 3
`
`1.
`
`2.
`
`3.
`
`Materials Used. ........................................................................................... 3
`
`Testing Protocol and Equipment. ................................................................ 8
`
`Results and Findings. .................................................................................. 8
`
`REQUIRED DISCLOSURES. ......................................................................................... 10
`
`FUTURE OPINIONS. ...................................................................................................... 11
`
`IV.
`
`V.
`
`
`
`i
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 4 of 15 PageID #: 48166
`
`I.
`
`INTRODUCTION.
`
`1.
`
`I, Dr. Gregory MacMichael, having been retained to testify as an expert in this case
`
`on behalf of Mylan Pharmaceuticals Inc. (“Mylan”) in the above-captioned action submit this
`
`Supplemental Responsive Expert Report in the above identified proceeding.
`
`2.
`
`I am the same Gregory MacMichael that submitted Opening Expert Reports in this
`
`case dated February 2, 2023 (“MacMichael Opening Reports”) and Responsive Expert Report of
`
`Gregory MacMichael, Ph.D. Regarding the Non-Infringement of the Asserted Claims of U.S.
`
`Patent No. 11,084,865 dated March 2, 2023 (“MacMichael Responsive Report”). I am also the
`
`same Gregory MacMichael that submitted a declaration entitled “Declaration of Gregory
`
`MacMichael, Ph.D. in Support of Defendant’s Claim Construction Brief” dated November 28,
`
`2022 (“MacMichael Declaration”). I incorporate by reference the MacMichael Responsive
`
`Report, the MacMichael Declaration, and all associated Exhibits to the extent relevant and
`
`necessary, and reserve the right to provide testimony on any issues or subject matter contained
`
`therein.
`
`3.
`
`This Supplement discloses my opinions, and the bases and reasons supporting my
`
`opinions, regarding, among other things, issues that I understand relate to Regeneron
`
`Pharmaceuticals, Inc.’s (“Plaintiff” or “Regeneron”) claims for alleged infringement of U.S. Patent
`
`No. 11,084,865 (“the ’865 patent”) including in response to the Opening Expert Report of
`
`Bernhardt L. Trout, Ph.D., dated February 2, 2023 (“Trout Report”).
`
`4.
`
`This Supplement sets forth the additional opinions I have formed based on
`
`information available as of the date below. In the event Regeneron submits any expert report or
`
`other response to the subject matter addressed in this Report, I reserve the right to respond to such
`
`submission. I expect to be called to testify at trial in the above-captioned action.
`
`1
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 5 of 15 PageID #: 48167
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 5of15 PagelD #: 48167
`
`I.
`
`PROFESSIONAL QUALIFICATIONS AND BACKGROUND.
`
`5.
`
`Details regarding my background, education, and experience are summarized in
`
`paragraphs 2-14 of the MacMichael Opening Reports and are incorporated by reference herein.
`
`(See also MacMichael Declaration {ff 3-14).
`
`6.
`
`7.
`
`A copy of my current curriculumvitae is attached to this Report as Exhibit A.
`
`In forming my opinions in this Report, the materials I have considered, in addition
`
`to my experience, education, and training, are identified herein, in the MacMichael Opening
`
`Reports, the MacMichael Responsive Report, the MacMichael Declaration, and/or in Exhibit B.
`
`I.
`
`SUPPLEMENTAL ANALYSIS.
`
`A.
`
`8.
`
`CLAIM 18.
`
`Claim 18 of the ’865 patent recites as follows (along with certain unasserted claims
`
`from whichasserted claim 18 depends):!
`
`Claim 1
`[UNASSERTED]
`
`A vial comprising an ophthalmic formulation suitable for intravitreal
`administration that comprises:
`
`a vascular endothelial growth factor (VEGF) antagonist
`
`an organic co-solvent,
`
`a buffer, and
`
`a stabilizing agent,
`
`wherein said VEGFantagonist fusion protein is glycosylated and
`comprises amino acids 27-457 of SEQ ID NO:4;and
`
`wherein at least 98% of the VEGFantagonist is present in native
`conformation following storage at 5° C. for two months as measured by
`size exclusion chromatography.
`
`Thevial of claim 2, wherein said organic co-solvent comprises 0.01% to
`
`Thevial of claim 1, wherein the concentration of said VEGF antagonist
`Claim 2
`[UNASSERTED]_|fusion protein is 40 mg/ml, and wherein said organic co-solvent
`comprises polysorbate.
`
`1 As stated in the MacMichael Opening Reports, I understand that Regeneronis currently asserting
`claims 4, 7, 9, 11, and 14-18 (i.e., the “Asserted Claims”).
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 6 of 15 PageID #: 48168
`
`
`
`[UNASSERTED]
`
`3% polysorbate 20.
`
` Claim 18
`
`Thevial of claim 5, wherein said formulation does not contain
`phosphate.
`
`(865 patent at claims 1-2, 5, 18).
`
`In my opinion, the POSA would understand that claim 18
`
`requires that the formulation contained in the vial does not contain phosphate.
`
`B.
`
`9.
`
`MYLAN’s M710 BLA Propwuct DoEs Not INFRINGE CLAIM18.
`
`In myopinion, Dr. Trout’s opening expert report did not prove that Mylan’s M710
`
`BLA Product infringes claim 18 of the ’865 patent under either Mylan’s Proposed Constructions
`
`or Regeneron’s Claim Construction Proposals. (Trout Report at §§ 141-142). After reviewing Dr.
`
`Trout’s opinion, I requested testing of Mylan’s M710 BLA Product to determine if Mylan’s M710
`
`BLAProduct does or does not contain phosphate. The results of this testing are the subject of this
`
`supplementalreport.
`
`10.
`
`[have reviewed the testing performed by Emery Pharmaattached as Exhibits C-F,
`
`further discussion of which can be found below.
`
`I have also had the opportunity to discuss the
`
`testing with Emery Pharma and agree that the testing was performed correctly and accurately.
`
`1.
`
`Materials Used.
`
`11.|Emery Pharma received samples of Mylan’s M710 BLA Product identified as
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 7 of 15 PageID #: 48169
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 7 of 15 PagelD #: 48169
`
`(Exhibit G). The samples were shipped on March 16, 2023, from Thermofisher Scientific and
`
`arrived at Emery Pharma on March 17, 2023. The samples were kept at 2-8 °C during shipping:
`
`Bling reference
`Liendl
`252 714 6367
`
`Account$ 23989
`
`Danel Ancrews
`Tharmofsher Scasniific
`5900 Maron Luther King Hwy
`
`Greenvéle NC 27834 US
`
`‘ShipmentInformation
`Full description ofcontents
`PHARMACEUTICAL - RESEARCHANVESTIGATIONAL.Reingerated +20 to +8C
`
`23112542B/Ann
`
`-
`
`Rec'd by WC {nama}
`ST]
`NA
`
`=
`
`ewnet
`
`Neelajan Bose
`Emery Pharma
`1000 Atlante Ave. Suile 410
`
`Mameda CA 9450! US
`
`‘Special handing
`PICKUP. promde t S6L at 2-8¢ with TT. Use ACCT# 9710
`
`DELIVERY teave TT win consgnee
`
`amiPier V4/23|"(im Coselh
`
`Eanatere of shipper oeamipper's ageat
`—
`‘Signature of consignee or consignee's agent
`LE (305|(Loe
`
`
`(Exhibit G). Upon receipt at Emery Pharma on March 17, 2023, the samples werestored at
`
`2-8 °C. Pictures were taken of the samples as shown below:
`
`
`
`
`Doesthis angment contin cangerousgoods?
`Dimensions
`Cues
`$4 X 52X53
`cs
`no jo 1Mannedpeat +eee
`Cecaredvalue for carriage
`Dectered value for customs
`uso
`000
`WORLDCOUNIER'SUAmITY 19LintTED 460 2V8/EE1TO WORLO COURSCONDTIONSOFCANALAOE yonIEHARE AUAAABLEAT AAT WORLD COURIER OPPEE AnD At
`harsconnet
`*
`<iaruansimmeeseneceaaPeun Print name of consignagar consignee's agent
`
`vom
`mo
`
`-
`career +secteranen ntrenner
`CO YES
`Check if surcharge elected
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 8 of 15 PageID #: 48170
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 8 of 15 PagelD #: 48170
`
`5
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 9 of 15 PageID #: 48171
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 9 of 15 PagelD #: 48171
`
`6
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 10 of 15 PageID #:
`48172
`
`12.
`
`Once received, the samples were stored at 2-8 °C in accordance to the conditions
`
`set forth in the accompanying documents and the labels on the boxes. (Exhibits G-H). Emery
`
`Pharma performed testing on 3 vials of Mylan’s M710 BLA Product
`
`
`
`
`
`7
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 11 of 15 PageID #:
`48173
`
`2.
`
`Testing Protocol and Equipment.
`
`13.
`
`The testing protocol and equipment used for the phosphate test is described in
`
`Exhibit C. I have appended Exhibit C to this Report that includes the protocol that underlies the
`
`results below, Exhibit D that includes the laboratory notebook pages, Exhibit E that includes
`
`calibration curve and test sample data, and Exhibit F that includes the results.
`
`14.
`
`The testing protocol performed by Emery Pharma is listed in the document entitled
`
`PiPer™ Phosphate Assay Kit (P22061). (Exhibit C).
`
`15.
`
`16.
`
`A calibration curve was prepared according to the protocol. (Exhibits C-E).
`
`The fluorometric phosphate assay test was performed according to the protocol.
`
`(Exhibits C, D, and F).
`
`17.
`
`Spike recovery assessments were performed to determine whether analyte detection
`
`is affected by the sample matrix. (Exhibits C,D, and F).
`
`3.
`
`Results and Findings.
`
`18.
`
`Emery Pharma tested samples of Mylan’s M710 BLA Product using the procedures
`
`described in Exhibits C-E.
`
`19.
`
`The results of preparing the calibration curve according to the protocol is shown
`
`below:
`
`8
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 12 of 15 PageID #:
`48174
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 13 of 15 PageID #:
`48175
`
`
`
`(Exhibit F). These results show that the phosphate results are accurate for the detection of
`
`phosphate in the samples.
`
`22.
`
`In my opinion, Emery Pharma’s testing has been performed correctly and I am
`
`satisfied that the method used is capable of detecting phosphate at the levels shown in the chart
`
`above.
`
`23.
`
`The testing showed that Mylan’s M710 BLA Product does contain phosphate and,
`
`as such, in my opinion, does not infringe claim 18 of the ’865 patent.
`
`24.
`
`Furthermore, as Mylan’s M710 BLA Product contains phosphate, Dr. Trout has
`
`failed in paragraphs 141-42 of the Trout Report to show that Mylan’s M710 BLA Product infringes
`
`claim 18 of the ’865 patent.
`
`IV. REQUIRED DISCLOSURES.
`
`25.
`
`The terms of my retention, compensation, or the matters in which I have given
`
`testimony over the last four years have not changed since the MacMichael Opening Reports.
`
`10
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 14 of 15 PageID #:
`48176
`
`V.
`
`FUTURE OPINIONS.
`
`26.
`
`This Report sets forth the opinions I have formed based on information available
`
`as of the date of this Report. Because other as yet unknown and unidentified material may be
`
`introduced during this litigation, which may fall within my area of expertise, I may have relevant
`
`and important opinions regarding such as yet unknown and unidentified material. I reserve the
`
`right to be able to offer such opinions if they may become relevant or important as such material
`
`becomes known. I further reserve the right and intend to testify and offer additional opinions in
`
`response to any opinions offered by Regeneron or its purported experts.
`
`27.
`
`I further reserve the right to supplement or amend this Report based on additional
`
`information made available to me, including in light of ongoing fact discovery (including third
`
`party discovery) and any expert reports submitted on behalf of Regeneron, or in order to clarify
`
`the information provided herein. I also reserve the right to supplement or amend this Report in
`
`light of any claim interpretations (or changes or supplements thereto) made by the Court.
`
`11
`
`
`
`Case 1:22-cv-00061-TSK-JPM Document 623 Filed 09/01/23 Page 15 of 15 PageID #:
`48177
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
