U.S. Patent 9,463,114
`Petition for Inter Partes Review
`
`Docket No.: 129285-00012
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`PATENT:
`
`9,463,114
`
`INVENTORS: STEVEN A. ODRICH; LIANE C. GLAZER
`
`FILED:
`
`AUGUST 29, 2014
`
`ISSUED:
`
`OCTOBER 11, 2016
`
`TITLE:
`
`PUNCTAL PLUG WITH ACTIVE AGENT
`
`___________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`
`Ocular Therapeutix
`Petitioner
`
`v.
`
`Mati Therapeutics, Inc.
`Patent Owner
`
`Case IPR2019-00442
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,463,114
`UNDER 35 U.S.C. § 312 AND 37 C.F.R. § 42.104
`
`
`
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`
`TABLE OF CONTENTS
`
`
`
`I.
`
`II.
`
`IV.
`
`V.
`
`VI.
`
`INTRODUCTION............................................................................................ 1
`A. The Parties ................................................................................................ 1
`B. The ‘114 Patent Is Invalid ......................................................................... 2
` MANDATORY NOTICES .............................................................................. 3
`A. Real Party-in-Interest ................................................................................ 3
`B. Related Matters ......................................................................................... 3
`C. Counsel ..................................................................................................... 3
`D. Service Information ................................................................................... 4
` CERTIFICATION OF GROUNDS FOR STANDING .................................... 4
`III. OVERVIEW OF CHALLENGE AND RELIEF REQUESTED ....................... 4
`A. Prior Art Patents and Printed Publications ................................................. 4
`B. Relief Requested ....................................................................................... 5
` BACKGROUND OF THE TECHNOLOGY ................................................... 5
`A. Lacrimal Punctum and Canaliculus ........................................................... 5
`B. Punctal Plugs ............................................................................................. 6
`C. Ophthalmic Drug Delivery ........................................................................ 8
` THE ’114 PATENT ......................................................................................... 9
`A. Claims ....................................................................................................... 9
`B. Challenged Claims .................................................................................... 9
`C. Summary of the Specification ..................................................................12
`D. Summary of the Prosecution History ........................................................13
`E. Level of Ordinary Skill in the Art .............................................................18
`
`CLAIM CONSTRUCTION .....................................................................19
`VII. THE PRIOR ART ....................................................................................22
`A. Schmitt .....................................................................................................22
`B. Higuchi ....................................................................................................24
`C. Cagle ........................................................................................................26
`D. Physician’s Desk Reference for Ophthalmic Medicines (2003) ................26
`
`VIII.
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`
` GROUNDS FOR CHALLENGE ....................................................................27
`A. Ground 1: Claims 1, 3, 6-8, 10 and 13 Are Anticipated by Schmitt ........29
`B. Ground 2: Claims 1, 3, 6-8, 10, 13, and 14 Are Obvious Over Schmitt in
`View of Higuchi .......................................................................................42
`C. Ground 3: Claims 1, 3, 6-8, 10, 13, and 14 Are Obvious Over Schmitt in
`View of PDR (2003) ................................................................................53
`D. Ground 4: Claims 1, 3, 5-8, 10, and 12-14 Are Obvious Over Schmitt in
`View of Cagle ..........................................................................................61
` Conclusion ......................................................................................................70
`
`IX.
`
`X.
`
`
`
`
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`TABLE OF EXHIBITS
`
`Description
`US Patent No. 9,463,114 to Odrich et al. (“‘114 Patent”)
`Declaration of Reza Dana, M.D., executed December 14, 2018
`(“Dana Decl.”)
`Curriculum Vitae of Reza Dana, M.D. (“Dana CV”)
`US Patent No. 5,469,867 to Schmitt (filed September 2, 1992)
`(“Schmitt”)
`US Patent No. 3,993,071 to Higuchi et al. (filed July 24, 1975)
`(“Higuchi”)
`Physician’s Desk Reference for Ophthalmic Medicines (2003)
`(published 2002) (“PDR2003”)
`US Patent No. 6,509,327 to Cagle et al. (filed May 19, 2000)
`(“Cagle”)
`File History of US Application 14/472,844 (“’844 FH”)
`W. Foulds “Intra-Canalicular Gelatin Implants In the Treatment
`of Kerato-Conjunctivitic Sicca,” BRIT. J. OPHTHAL. 45:625
`(1961) (“Foulds”)
`STEDMAN’S CONCISE MEDICAL DICTIONARY FOR THE HEALTH
`PROFESSIONS, 3rd Ed., Dirckx, J. (ed.) (“Stedman”)
`Snell, R., CLINICAL ANATOMY FOR MEDICAL STUDENTS, 5th Ed.
`(1995) (“Snell”)
`US Patent No. 3,949,750 to Freeman (filed October 7, 1974)
`(“Freeman”)
`US Patent No. 6,196,993 to Cohan et al. (filed April 19, 1999)
`(“Cohan”)
`Miller, J. and Wolf, E.H., “Antazoline phosphate and
`naphazoline hydrochloride, singly and in combination for the
`treatment of allergic conjunctivitis,” ANN. ALLERGY, 35:81-86
`(1975) (“Miller”)
`US Patent No 5,283,063 to Freeman (filed Jan. 31, 1992)
`(“Freeman 94”)
`US Patent No. 5,322,691 to Darougar et al. (filed June 29, 1993)
`(“Darougar”)
`File History of the ’202 Patent (“’202 FH”)
`US Patent No. 3,828,777 to Ness (filed November 8, 1971)
`(“Ness”)
`
`Exhibit
`Ex. 1001
`Ex. 1002
`
`Ex. 1003
`Ex. 1004
`
`Ex. 1005
`
`Ex. 1006
`
`Ex. 1007
`
`Ex. 1008
`Ex. 1009
`
`Ex. 1010
`
`Ex. 1011
`
`Ex. 1012
`
`Ex. 1013
`
`Ex. 1014
`
`Ex. 1015
`
`Ex. 1016
`
`Ex. 1017
`Ex. 1018
`
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`U.S. Patent 9,463,114
`US. Patent 9,463,114
`Petition for Inter Partes Review
`Petition for Inter Partes Review
`Berkow, R. ed., THE MERCK MANUAL, 13TH ED. (1977)
`Ex. 1019
`Berkow, R. ed., THE MERCK MANUAL, 13TH ED. (1977)
`Ex. 1019
`
`(“Merck”)
`(“Merck”)
`
`“CMC Chemical Profile,” icis.com (“CMC”)
`Ex. 1020
`“CMC Chemical Profile,” icis.com (“CMC”)
`Ex. 1020
`Ex. 1021
`Kibbe, A., ed., Handbook of Pharmaceutical Excipients 3rd Ed.
`Ex. 1021
`Kibbe, A., ed., Handbook of Pharmaceutical Excipients 3rd Ed.
`
`(2000) (“Handbook”)
`(2000) (“Handbook”)
`U.S. Patent No. 9,309,313, entitled “Therapeutic Compositions
`Ex. 1022
`US. Patent No. 9,309,313, entitled “Therapeutic Compositions
`Ex. 1022
`
`for Treatment of Ocular Inflammatory Disorders” (“Dana313”)
`for Treatment of Ocular Inflammatory Disorders” (“Dana313”)
`US Application Publication No. 2007/0265341, entitled
`US Application Publication No. 2007/0265341, entitled
`“Compositions and Methods for Treating Eye Disorders and
`“Compositions and Methods for Treating Eye Disorders and
`
`Conditions” (“Dana341”)
`Conditions” (“Dana341”)
`
`Netter, F.H., Atlas of Human Anatomy, 2nd E. (1997) (“Netter”)
`Ex. 1024
`Netter, F.H., Atlas of Human Anatomy, 2nd E. (1997) (“Netter”)
`EX. 1024
`Ex. 1025
`U.S. Pat. No. 5,902,598 to Chen et al. (filed Aug. 28, 1997)
`Ex. 1025
`US. Pat. No. 5,902,598 to Chen et al. (filed Aug. 28, 1997)
`
`(“Chen”)
`(“Chen”)
`US Application Publication No. 2005/0095269 to Ainpour et al.
`Ex. 1026
`US Application Publication No. 2005/0095269 to Ainpour et al.
`Ex. 1026
`
`(filed Nov. 4, 2003) (“Ainpour”)
`(filed Nov. 4, 2003) (“Ainpour”)
`US Patent No. 4,327,725 to Cortese et al. (filed Nov. 25, 1980)
`Ex. 1027
`US Patent No. 4,327,725 to Cortese et al. (filed Nov. 25, 1980)
`Ex. 1027
`
`(“Cortese”)
`(“Cortese”)
`US Patent No. 5,124,392 to Robertson et al. (filed May 31, 1990)
`US Patent No. 5,124,392 to Robertson et al. (filed May 31, 1990)
`(“Robertson”)
`(“Robertson”)
`Baxter et al., Punctal Plugs in the Management of Dry Eyes, 2
`Ex. 1029
`Baxter et al., Punctal Plugs in the Management of Dry Eyes, 2
`Ex. 1029
`
`THE OCULAR SURFACE, 255-265 (October 2004) (“Baxter”)
`THE OCULAR SURFACE, 255-265 (October 2004) (“Baxter”)
`
`
`
`
`
`
`
`Ex. 1023
`Ex. 1023
`
`Ex. 1028
`Ex. 1028
`
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`
`
`I.
`
`INTRODUCTION
`
`A. The Parties
`
`Petitioner Ocular Therapeutix, founded in 2006 and based in Bedford,
`
`Massachusetts, is an innovative biopharmaceutical company focused on the
`
`development and commercialization of therapies for various diseases and
`
`conditions of the eye. Currently, Ocular is developing the Dextenza® drug-eluting
`
`intracanalicular insert for treating post-surgical ocular pain and other ophthalmic
`
`conditions. On November 30, 2018, after extensive Phase 2 and Phase 3 studies,
`
`Ocular received FDA approval of Dextenza® for intracanalicular use for the
`
`treatment of ocular pain following ophthalmic surgery. Ocular expects to begin
`
`marketing Dextenza® during the first half of 2019.
`
`The patent owner, Mati Therapeutics, based in Austin, Texas, did not invent
`
`the technology claimed in the ’114 Patent but rather acquired the patent rights from
`
`another company, years after the original application in the chain of priority was
`
`filed. Mati has no products on the market. Nonetheless, aware of the impending
`
`FDA approval of the Dextenza® insert, Mati sent Ocular a letter dated October 18,
`
`2018, accusing the Dextenza® insert of infringing U.S. Patent No. 9,463,114 (the
`
`’114 Patent, Ex. 1001) and two other patents. This IPR is necessary to remove the
`
`cloud of Mati’s threats so that, now that the FDA has approved the Dextenza®
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`U.S. Patent 9,463,114
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`insert, Ocular can provide this important medical advancement to eye surgery
`
`patients.
`
`B.
`
`The ’114 Patent Is Invalid
`
`The ’114 Patent recites methods for administering an active agent to a
`
`subject by inserting a punctal plug into the subject’s punctal aperture, the punctal
`
`plug comprising an active and a hydrophilic polymer and/or porous or absorbent
`
`material and consisting of a constant diameter cylinder. The challenged claims
`
`were granted because the Examiner believed that “[t]he punctal plugs of the prior
`
`art all contain some sort of flange o[r] portion of greater diameter than the body of
`
`the plug” and “[t]herefore the insertion of cylindrical drug releasing implant of
`
`constant diameter for the entire length without a flange or other portion of greater
`
`diameter into the punctum of a subject is non-obvious.” Ex. 1008, ’844 FH, Notice
`
`of Allowability, 19. But, as explained below, cylinder-shaped punctal plugs—
`
`plugs without a flange or other portion of greater diameter—have been used and
`
`described in printed publications for generations. As just one example, Foulds
`
`(1961) describes and documents inserting cylindrical-shaped punctal plugs through
`
`the punctal aperture of human subjects for the treatment of kerato-conjunctivitis
`
`sicca. Ex. 1002, Decl., ¶32.
`
`Further, although a family member of the closest prior art, Schmitt, was
`
`before the Patent Office during prosecution, it was neither applied nor appreciated
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`U.S. Patent 9,463,114
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`by the Examiner. Schmitt discloses inserting a cylindrical-shaped punctal plug
`
`into the punctal aperture. Ex. 1004, Schmitt. Schmitt teaches that its plug may
`
`comprise a biological active, such as an antibiotic, as well as hydrophilic polymers
`
`and absorbent materials. Id. The person of ordinary skill in the art would have
`
`been motivated to combine the cylindrical-shaped punctal plug of Schmitt with
`
`other references disclosing medications for ophthalmic delivery, such as Higuchi
`
`(Ex. 1005), the Physician’s Desk Reference for Ophthalmic Medicines (Ex. 1006),
`
`and Cagle (Ex. 1007). Therefore, Schmitt anticipates most of the Challenged
`
`Claims and, in combination with Higuchi, the Physician’s Desk Reference, or
`
`Cagle, renders each of the Challenged Claims obvious. Ex. 1002, Decl., ¶41.
`
` MANDATORY NOTICES
`II.
`
`A. Real Party-in-Interest
`
`Ocular Therapeutix (“Petitioner”) is the real party in interest.
`
`B. Related Matters
`
`Currently, Ocular is not aware of any pending litigation related to the ’114
`
`Patent. Ocular is, however, aware of a co-pending IPR petition regarding U.S. Pat.
`
`No. 9,849,082, also filed by Ocular against the same patent owner, Mati
`
`Therapeutics. The ’082 Patent is not related to the ’114 Patent but is owned by the
`
`same company (Mati) and is directed to analogous ocular implant devices.
`
`C. Counsel
`
`Lead Counsel:
`
`Brian M. Seeve (Registration No. 71,721)
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`Backup Counsel: Kia L. Freeman (Registration No. 47,577)
`
`Backup Counsel: Erik Paul Belt (pro hac vice to be requested)
`
`Backup Counsel: Wyley S. Proctor (pro hac vice to be requested)
`
`Backup Counsel: Thomas F. Foley (Registration No. 76,384)
`
`D.
`
`Service Information
`
`E-mail: OCLIPR@mccarter.com
`
`Delivery Address: McCarter & English, 265 Franklin St., Boston, MA 02110
`
`Telephone: 617-449-6500
`
`Petitioner consents to service by email.
`
` CERTIFICATION OF GROUNDS FOR STANDING
`III.
`
`Petitioner certifies pursuant to Rule 42.104(a) that U.S. Patent No. 9,463,114
`
`(the “’114 Patent”) is available for inter partes review and that Petitioner is not
`
`barred or estopped from requesting an inter partes review on the grounds identified
`
`in this Petition.
`
` OVERVIEW OF CHALLENGE AND RELIEF REQUESTED
`IV.
`
`Pursuant to Rules 42.22(a)(1) and 42.104(b)(1)-(2), Petitioner challenges
`
`Claims 1, 3, 5-8, 10, and 12-14 of the ’114 Patent (the “Challenged Claims”) and
`
`requests that each Challenged Claim be canceled.
`
`A.
`
`Prior Art Patents and Printed Publications
`
`Petitioner relies upon the patents and printed publications listed in the Table
`
`of Exhibits, including:
`
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`1. U.S. Patent No. 5,469,867 to Schmitt (filed September 2, 1992) (“Schmitt,”
`
`Ex. 1004).
`
`2. U.S. Patent No. 3,993,071 to Higuchi et al. (filed July 24, 1975) (“Higuchi,”
`
`Ex. 1005).
`
`3. Physician’s Desk Reference for Ophthalmic Medicines (2003) (published
`
`2002) (“PDR (2003),” Ex. 1006).
`
`4. U.S. Patent No. 6,509,327 to Cagle et al. (filed May 19, 2000) (“Cagle,” Ex.
`
`1007).
`
`B. Relief Requested
`
`Petitioner requests that the Patent Trial and Appeal Board cancel the
`
`Challenged Claims because they are unpatentable under 35 U.S.C. §§ 102 and 103
`
`as set forth in this Petition. This conclusion is supported by the declaration of Dr.
`
`Reza Dana, MD, M.Sc., MPH (“Decl.,” Ex. 1002), filed herewith.
`
`V.
`
` BACKGROUND OF THE TECHNOLOGY
`
`A. Lacrimal Punctum and Canaliculus
`
`The tear duct is comprised of a series of channels and reservoirs, including
`
`the lacrimal canaliculus, the canal running from the inner corner of the eye to the
`
`lacrimal sac, and the lacrimal punctum, the opening to the lacrimal canaliculus.
`
`See, e.g., Ex. 1002, Decl., ¶29; see also Ex. 1010, STEDMAN’S CONCISE MEDICAL
`
`DICTIONARY FOR THE HEALTH PROFESSIONS, 3rd Ed. (“Stedman”), 5. Portions of
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`the lacrimal system are shown in the following image from Ex. 1024, ATLAS OF
`
`HUMAN ANATOMY, 2nd Ed. (“Netter”), 7. Ex. 1002, Decl., ¶29.
`
`The punctum and canaliculus allow tears to drain away from the eye; “the
`
`punctum and canaliculus serve to carry tears down into the nose.” Ex. 1011, Snell,
`
`R., CLINICAL ANATOMY FOR MEDICAL STUDENTS, 5th Ed. (“Snell”), 6; Ex. 1002,
`
`
`
`Decl., ¶31.
`
`B.
`
`Punctal Plugs
`
`Since at least the 1960s, doctors have treated ophthalmic conditions by
`
`placing cylindrical-shaped inserts through the punctum and into the lacrimal
`
`canaliculus. For example, Foulds (1961), entitled “Intra-Canalicular Gelatin
`
`Implants in the Treatment of Kerato-Conjunctivitis Sicca,” teaches occluding the
`
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`lacrimal punctum using “fine solid rods of gelatin.” Ex. 1009, Foulds, 4.
`
`Specifically, as described in Foulds and illustrated in Foulds’ Figures 1 and 2, a
`
`“gelatin rod is inserted in one movement so as to fill the whole length of the
`
`canaliculus” for treatment of kerato-conjunctivitis. Id., 4; see also id., Fig. 1, Fig. 2
`
`(reproduced below). Ex. 1002, Decl., ¶32.
`
`
`
`Since the 1960s, cylindrical punctal plugs, such as those described in Foulds,
`
`have evolved into plugs of different shapes and comprising different materials. For
`
`example, U.S. 3,949,750 to Freeman, issued in 1976, teaches punctal plugs
`
`comprising hydrophilic polymers in which the traditional cylinder-shaped plug
`
`body is sandwiched between “a projecting tip or barb portion” and “a larger
`
`smooth head portion…” Ex. 1012, Freeman, 2:1-6; see also id., Abstract (“The
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`U.S. Patent 9,463,114
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`rod-like plug is formed with an oversized tip or barb portion … a smaller neck or
`
`waist portion … and a relatively larger, smooth head portion…”). Ex. 1002, Decl.,
`
`¶33.
`
`Like other ocular devices, punctal plugs have long been used as drug
`
`delivery devices. Freeman, for example, teaches punctal plugs used as an
`
`“effective vehicle for dispensing ophthalmic medication on a sustained release
`
`basis” in “situations involving infection, inflammation or other ocular diseases.”
`
`Ex. 1012, Freeman, 2:27-31; see also id., 1:8-14. Similarly, Schmitt, issued in
`
`1995, teaches that its punctal plugs can comprise “a biologically active substance
`
`that could leach out” of its punctal plug, and that “[t]hese biological active
`
`substances could be … antibiotics and the like.” Ex. 1004, Schmitt, 8:34-39. In
`
`another example, U.S. 6,196,993 to Cohan teaches using a punctal plug to release
`
`active agents into the eye, such active agents including latanoprost. Ex. 1013,
`
`Cohan, 7:5-12, Abstract. Ex. 1002, Decl., ¶34.
`
`As Dr. Dana explains, numerous other drug-eluting punctal plugs and other
`
`ocular inserts were described and used before 2004. Ex. 1002, Decl., ¶35-40.
`
`C. Ophthalmic Drug Delivery
`
`Doctors routinely administer a wide range of medications to the ocular area.
`
`Such actives include topical medications for treating ocular conditions, such as
`
`glaucoma, infection and allergic conjunctivitis. See, e.g., Ex. 1002, Decl., ¶35; Ex.
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`U.S. Patent 9,463,114
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`1006, PHYSICIAN’S DESK REFERENCE OF OPHTHALMIC MEDICINES (2003)
`
`(“PDR2003”), 22 (identifying travoprost as prostaglandin and agent for treatment
`
`of glaucoma); Ex. 1014, Miller, J. and Wolf, E.H., “Antazoline phosphate and
`
`naphazoline hydrochloride, singly and in combination for the treatment of allergic
`
`conjunctivitis – a controlled, double-blind clinical trial,” (“Miller”), 1-6. Ex. 1002,
`
`Decl., ¶35
`
` THE ’114 PATENT
`VI.
`
`A. Claims
`
`U.S. Patent No. 9,463,114 (“the ’114 Patent”), entitled “Punctal Plug with
`
`Active Agent” issued to Steven Odrich and Liane Glazer on April 15, 2004. The
`
`’114 Patent claims priority to U.S. Ser. No. 10/825,047, filed April 15, 2004, the
`
`earliest possible priority date for the ’114 Patent.
`
`B. Challenged Claims
`
`Petitioner challenges Claims 1, 3, 5-8, 10, and 12-14 (“Challenged Claims”).
`
`Petitioner challenges each of the three independent claims: claims 1, 8, and 14.
`
`Claims 1 and 8 are identical, except that claim 1 recites that the plug comprise “a
`
`porous or absorbent material,” while claim 8 recites that the plug comprise “a
`
`hydrophilic polymer.” Claims 8 and 14 are identical, except that claim 14 lists
`
`only a subset of the actives recited in claim 8. Specifically, the independent claims
`
`of the ’114 Patent recite:
`
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`U.S. Patent 9,463,114
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`1. A method for administering an active agent to a subject using a
`
`punctal plug, the method comprising:
`
`inserting the punctal plug into a punctal aperture of the subject,
`
`wherein the composition of the punctal plug comprises:
`
`a) an active agent selected from the group consisting of topical
`
`prostaglandin; latanoprost; travoprost; bimatoprost; a medication for
`
`treatment of a corneal
`
`infection; ciprofloxacin; moxifloxacin;
`
`gatifloxacin; a systemic medication; a medication for treating
`
`hypertension; atenolol; nifedipine; hydrochlorothiazide; and a
`
`medication for treating allergic conjunctivitis, and
`
`b) a porous or absorbent material, and
`
`wherein the shape of the punctal plug consists of a constant diameter
`
`cylinder configured to be inserted into a canalicular puncta of the
`
`subject.
`
`
`
`8. A method for administering an active agent to a subject using a
`
`punctal plug, the method comprising:
`
`inserting the punctal plug into a punctal aperture of the subject,
`
`wherein the composition of the punctal plug comprises:
`
`a) an active agent selected from the group consisting of topical
`
`prostaglandin; latanoprost; travoprost; bimatoprost; a medication for
`
`treatment of a corneal
`
`infection; ciprofloxacin; moxifloxacin;
`
`gatifloxacin; a systemic medication; a medication for treating
`
`hypertension; atenolol; nifedipine; hydrochlorothiazide; and a
`
`medication for treating allergic conjunctivitis, and
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`U.S. Patent 9,463,114
`Petition for Inter Partes Review
`
`b) a hydrophilic polymer, and
`
`wherein the shape of the punctal plug consists of a constant diameter
`
`cylinder configured to be inserted into a canalicular puncta of the
`
`subject.
`
`
`
`14. A method for administering an active agent to a subject using a
`
`punctal plug, the method comprising:
`
`inserting the punctal plug into a punctal aperture of the subject,
`
`wherein the composition of the punctal plug comprises:
`
`a) an active agent wherein the active agent is selected from the group
`
`comprising: travoprost; moxifloxacin; and a medication for treating
`
`allergic conjunctivitis, and
`
`b) a hydrophilic polymer,
`
`wherein the shape of the punctal plug consists of a constant diameter
`
`cylinder configured to be inserted into a canalicular puncta of the
`
`subject.
`
`The dependent claims limit their respective independent claims to punctal
`
`plugs having a specific topical prostaglandin, specific categories of medications or
`
`specific medications, and hydrophilic polymers. Specifically, claims 3 and 10,
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`which depend from claims 1 and 8, respectively, recite “wherein the topical
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`prostaglandin is travoprost.” Claims 5 and 12, which depend from claims 1 and 8,
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`respectively, recite “wherein the active agent is moxifloxacin.” Claims 6 and 13,
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`which depend from claims 1 and 8 respectively, recite “wherein the active agent is
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`a medication for the topical treatment of glaucoma or corneal infection.” Finally,
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`claim 7, which depends from claim 1, recites “[t]he punctal plug of claim 1,
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`wherein the plug body comprises hydrophilic polymers.”
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`C.
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`Summary of the Specification
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`The ’114 Patent discloses methods for administering an active agent to a
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`subject using an ocular insert such as a punctal plug. Ex. 1001, ’114 Patent,
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`Abstract. Ex. 1002, Decl., ¶43.
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`The ’114 Patent specification acknowledges that “[p]unctal plugs are known
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`which are made in suitable dimensions and of suitable materials to be removably
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`inserted into the upper and/or lower punctal apertures or punctum of the eye…”
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`and that “[s]uch plugs are known to be made of suitable materials, such as
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`polymers, for example polytetrafluorethylene (known by the trademark TEFLON),
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`or hydroxyethylmethacrylate (HEMA), hydrophilic polymer, methyl methacrylate,
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`or silicon…” Ex. 1001, ’114 Patent, 1:13-22.
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` The specification further
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`acknowledges “[i]t was known to apply an active agent … to the inner surface of a
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`patch which can be worn against the skin of a subject for transdermally
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`administering the active agent to the subject.” Id., 1:25-28. Ex. 1002, Decl., ¶43.
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`The specification describes punctal plugs of various shapes and materials.
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`Ex. 1001, ’114 Patent, 2:11-13 (“Plug 10 has a large stopper structure 14
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`connected to the outer end of stem 12 for seating against the aperture”); id., 2:17-
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`20 (“Implant 10a is a substantially cylindrical and solid collagen plug that has been
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`inserted into the upper punctum or tear duct … while lower implant 10b is hollow
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`like a straw for the passage of tears. Implant 10b includes a tapered shaft or stem
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`12a with a flared open end….”). The specification states, “Unlike the usual tear
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`stopping punctal plug, the hollow implant of the present invention provides a very
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`different drug administering method, scheme and structure.” Id., 2:47-50. Ex.
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`1002, Decl., ¶44.
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`
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`The specification states, “This invention is meant to embody all implants or
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`devices which are implanted into the eye-lid canalicular puncta of the naso-
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`lacrimal system with the goal of delivering drug to the eye or to the body.” Id., 3:9-
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`12. Ex. 1002, Decl., ¶45.
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`D.
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`Summary of the Prosecution History
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`Applicant Mati Therapeutics, Inc. filed Application No. 14/472,844 (“’844
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`Application”) on August 29, 2014. The ’844 Application is a continuation of
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`U.S. Patent 9,463,114
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`Application No. 13/533,676, filed June 26, 2012 and since abandoned, which is a
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`continuation of Application No. 12/604,202, filed October 22, 2009 and since
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`abandoned, which is a divisional of Application No. 10/825,047, filed April 14,
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`2004 and since abandoned.
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`1.
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`Examiner Findings and Applicant Admissions
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`During prosecution of the ’844 Application, the Examiner found, and the
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`Applicant acknowledged, that the prior art discloses punctal plugs for delivery of
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`active agents comprising, inter alia, hydrophilic polymers and actives agents. For
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`example, the Examiner found that Freeman discloses punctal plugs for delivery of
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`actives and insertion into the punctum:
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`Freeman discloses a plug suitable for insertion into the upper and/or
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`lower punctal apertures, reading on a punctal plug (e.g., abstract,
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`figure 3). The plug can serve as an effective vehicle for dispensing
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`ophthalmic medication ….
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`Ex. 1008, ’844 FH, 96 (8/28/2015 Office Action); see also Ex. 1012, Freeman.
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`The Examiner also found that “Freeman discloses that the punctal plug can be
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`made from HEMA (hydroxyethylmethacrylate; col 4, ln 40 onward), a hydrophilic
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`polymer.” Ex. 1008, ’844 FH, 167 (9/22/2015 Office Action) (emphasis added).
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`In addition, the Examiner found that the person of ordinary skill in the art
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`would have been motivated to combine references disclosing punctal plugs for
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`delivery of medications with references disclosing ophthalmic medications with a
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`reasonable expectation of success. For example, the Examiner found that the
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`person of ordinary skill would have been motivated to combine Freeman’s punctal
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`plug with the disclosure of useful glaucoma medications:
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`It would have been obvious to the person of ordinary skill in the art at
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`the time the invention was made to incorporate a drug such as
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`bimatoprost and travoprost into the drug releasing implants of
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`Freeman and Cohan. The person of ordinary skill in the art would
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`have been motivated to make those modifications and reasonably
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`would have expected success because a variety of drugs can be
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`delivered using these devices as taught by Freeman and Cohan as
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`Hellberg et al. discloses the usefulness of latanoprost, bimatoprost and
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`travoprost in the treatment of ocular conditions. The person of
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`ordinary skill in the art can readily select the appropriate drugs to
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`include in a drug releasing implant from those that are known in the
`prior art.
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`Ex. 1008, ’844 FH, 168 (9/22/2015 Office Action) (emphases added). For the same
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`reasons, the Examiner held that it would have been obvious to the person of
`
`ordinary skill to combine Freeman’s drug-releasing punctal plug with a reference
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`disclosing moxifloxacin for ophthalmic, otic, and nasal administration. Id., 169.
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`2.
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`Alleged Points of Novelty: Cylindrical Shape and Plug Size
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`Rather than contradict these findings, the Applicant focused on the alleged
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`novelty of the shape and size of its claimed punctual plugs. Specifically, the
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`Applicant argued that the prior art failed to disclose “cylindrical” drug dispensing
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`punctal plugs of a size capable of being inserted into the human eye.
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`First, the Applicant’s principle argument throughout prosecution was that
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`the cited prior art failed to disclose cylindrical-shaped punctal plugs. After the
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`Examiner rejected all of the originally proposed claims, the Applicant cancelled
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`those claims and proposed new claims, reciting, inter alia, “[a] punctal plug
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`comprising a cylindrical plug body configured to be inserted into a canalicular
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`puncta ….” Ex. 1008, ’844 FH, 179 (8/30/2015 Response). The Applicant argued
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`that the cited prior art failed to disclose the newly-claimed “cylindrical plug body”
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`because the punctal plugs of the prior art allegedly comprised a wider portion that
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`sits outside the punctum:
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`[A] cylindrical shaped plug (e.g. 10a) does not included [sic] a flared
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`end 12b that sits at our [sic] outside the punctum aperture, or a
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`mushroom shaped stopper 14a for setting or retaining the location of
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`the implant in the tear duct. In contrast, a cylindrical shaped plug sits
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`within the canaliculus (intracanalicular).
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`Id., 128. The Examiner maintained the rejections of the claims despite the new
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`“cylindrical plug body” limitation. Id., 163-73 (9/22/2015 Office Action). The
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`Applicant tried to amend the “cylindrical” limitation multiple times to overcome
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`the cited art, but the Office refused to enter the amendments. Id., 137-45
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`(10/14/2015 Advisory Action); 111-15 (11/12/2015 Advisory Action). In
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`attempting to amend the claims, the Applicant reiterated its argument that the cited
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`references failed to disclose a “cylindrical shaped punctal plug.” Id., 128
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`(10/27/2015 Response). The Office rejected this argument. Id., 91-107 (12/3/2015
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`Office Action). Eventually, the Applicant amended the claims to recite “wherein
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`the punctal plug consists of a constant diameter configured to be inserted into a
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`canalicular puncta.” Id., 78 (2/4/2016 Response).
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`Although this amendment overcame some rejections, the Examiner rejected
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`all pending claims as anticipated by, and obvious in view of, U.S. 5,322,691 to
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`Darougar, which discloses an ocular insert device for sustained release of a drug.
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`Id., 67-73 (3/16/2016 Office Action). In response, the Applicant argued that
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`Darougar is not enabled as prior art because “[t]he device of Darouger et al. is
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`physically too large[] to be placed in a punctum.” Id., 83 (2/4/2016 Response); see
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`also Ex. 1016, Darougar. Following additional attempts to amend and further
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`rejections, the Examiner suggested during an interview that method of use claims
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`could overcome Darougar. Ex. 1008, ’844 FH, 44 (4/27/2016 Interview Summary).
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`The Applicant amended the claims to their present form, amending the apparatus
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`claims to method claims. Id., 32-34 (6/1/2016 Amendment). The Applicant
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`argued, inter alia, “Darouger et al. do not disclose, teach or reasonably suggest the
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`active step of inserting a punctal plug into a punctal aperture of a s