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`Part of the problem might reside with the regulatory process itself. The process for
`clearance of a new drug is complex and as the knowledge base concerning dry eye disease
`expands, the scientific basis for drug testing changes. According to Michael A. Lemp, MD,
`clinical professor at Georgetown and George Washington universities, "it was anticipated
`that the FDA would issue new guidelines for clinical trials in dry eye disease several years
`ago, but these have not been made public. The delay may rest with senior management
`within the Agency."
`
`The result is that there is no "one-stop shopping" source where would-be sponsors can learn
`the guidelines for clinical trial endpoints. Instead, sponsors must go to the FDA and make a
`proposal as to how they would perform a clinical trial; the FDA reviews the proposal and
`informs the sponsor if it is acceptable, or which portions are acceptable or unacceptable.
`
`"While the FDA is quite open to these inquires and willing to listen to novel ap proaches,
`many times companies new to this field feel as if they are guessing what the FDA wants,"
`Dr. Lemp explains. "They wonder if the FDA has changed what is acceptable since the last
`time they heard. It's like trying to read the tea leaves."
`
`Chugging Along
`
`Despite the regulatory hurdles, some dry eye drugs are making slow but steady progress
`toward beleaguered physicians and their patients. Most are anti-inflammatories, so their
`approval would fulfill a wish of Dr. Trattler's. "I use pulses of topical steroids frequently for
`dry eye patients, and if there were additional anti—inflammatory drugs that could work in
`this area, that would be very helpful for patients, since dry eye is an inflammatory
`condition."
`
`0 EGP-437. The closest drug to the goal is EyeGate's EGP-437. Currently in a phase 3
`efficacy study, it's a dexamethasonederived corticosteroid solution delivered to the eye via
`an iontophoretic drug delivery system that enables the drug to overcome the problem of low
`bioavailability that limits other topical agents. "You have to try to bypass natural barriers
`that are in place: the tear film and cornea," Mr. From says. "It's very difficult to get a large
`quantity of drug into the front of the eye, or any drug to the posterior pole of the eye for
`retinal diseases." Iontophoresis also allows EGP-437 to bypass the method physicians have
`had to resort to deliver large quantities of drug into the eye: needles.
`
`The doughnut-shaped applicator holds a sponge saturated with drug; the applicator is
`placed on the sclera after a topical anesthetic is applied to prevent the patient's blinking. An
`electrode at the base of the applicator is connected to a small, handheld generator that
`supplies a charge. A negatively charged drug in the foam portion gets a negative charge to
`the electrode, thus using the principle of electrorepulsion to push the drug at a high velocity
`into the eye.
`
`The process, Mr. From says, requires only a couple of minutes. "Depending on how high the
`current is, or how long we leave this on the eye, will dictate how much drug goes into the
`eye and how deep it penetrates into the eye."
`
`EGP-437 is a small molecule. In its recently-completed phase 2 study, it was able to treat
`multiple signs and symptoms of dry eye, rather than just one in each category, Mr. From
`says, "So we actually had the lucky advantage of being able to choose the best sign and the
`best symptom for our phase 3 trial." Even better, he says, was its onset of action, which
`begins within hours. "If you're a Sj6gren's patient and you have severe dry eye, you are in a
`lot of discomfort and pain" and at risk for scarring, Mr. From explains. Such patients would
`welcome a therapy with rapid onset of action. "No other drug that I'm aware of works as
`quickly as our drug is working," he says.
`
`Although data from EyeGate's 83-patient phase 2 trial are not yet available, the company
`did say that staining decreased in both fluorescein and lissamine green dyes, that
`conjunctival redness was reduced and that tear film breakup time increased.
`
`As for dosage, the drug would be administered in a physician's office, probably on a
`quarterly basis, according to Mr. From, depending on severity. The company has begun
`
`EXHIBIT 1004 (Part 4 of 4)
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`enrolling patients for the phase 3 clinical trial of approximately 180 planned. Mr. From
`anticipates that the trial should be completed during the first quarter of 2011, with top-line
`data available at the end of that period.
`
`He describes EyeGate's approach as acute therapy for a chronic problem. "We are able to
`put so much drug in so quickly to the tissues of the eye that we're knocking down the
`inflammatory cascade very rapidly. The drug doesn't stay in the eye very long, but the
`pharmacological effect lasts for a long time."
`
`0 CF101. Can—Fite BioPharma Ltd. recently opened an Investigational New Drug application
`(IND) with the FDA for a phase 3 study of its lead drug, CF101, for treatment of moderate
`to severe dry eye disease. Dr. Pnina Fishman, Can-Fite's CEO, says that CF101 exerts an
`anti-inflammatory effect and also an immunomodulatory one. The study will be initiated in
`few months.
`
`An earlier phase 2 study, in which CF101 was taken orally as a monotherapy for 12 weeks,
`showed a statistically significant benefit in the clearing of fluorescein staining in the nasal,
`temporal, pupillary and inferior cornea, the company reports. CF101 also was found to be
`safe and well tolerated in the Phase 2. Further, the study showed a decrease in intraocular
`pressure in patients with dry eye, findings that have prompted Can—Fite to initiate a phase 2
`clinical study for the drug's treatment of glaucoma.
`
`The randomized, double-masked phase 3 trial will compare two oral doses of CF101 to
`placebo. Approximately 240 patients will be enrolled at multiple centers, to be treated for 24
`weeks. The clinical endpoints are improvement of corneal fluorescein staining, tear
`production and dry eye symptom score.
`
`0 Low-dose bromfenac. Ista Pharmaceuticals’ phase 2 trial of low-dose bromfenac
`(Remura) demonstrated improvement in both a key sign (lissamine green staining) and in
`symptoms (as measured by the Ocular Surface Disease Index) of dry eye in 38 patients
`over a six—week period. Further, patients treated with low-dose bromfenac maintained the
`improvement in signs and symptoms for 10 days after discontinuing treatment. The
`company is currently in the process of initiating the efficacy portion of the phase 3 program,
`which will entail two studies with a total of approximately 1,000 patients followed over a six-
`week period, according to Dr. Chandler. The safety portion of the phase 3 trial is tentatively
`scheduled to begin later this year and will comprise a six-month and a 12-month trial, with
`a total of approximately 4,000 patients.
`
`Dr. Chandler notes that low-dose bromfenac could address the impact of inflammation on
`the ocular surface, a central feature of dry eye. "Controlling inflammation could both quiet
`the symptoms — that is, irritation, dryness, gritty, sandy feeling, burning in some cases —
`and improve the signs, such as staining, of ocular surface disease," he explains. The
`approach yields a dual benefit, Dr. Chandler contends, because of bromfenac's efficacy in
`dealing with pain as well as its ability to interrupt the inflammatory cycle, thereby allowing
`the ocular surface to heal. "There are very few medications that truly address the
`inflammatory cascade that is central to the disease while improving patient comfort," he
`says.
`
`Although the inflammatory etiology of dry eye remains theoretical, Dr. Chandler says it does
`explain the results seen in the phase 2 open—label trial. Dr. Chandler contends that low-dose
`bromfenac has an onset of action that is "much faster" than the approximately eight weeks
`required for topical cyclosporine. In studies completed to date, he says, the drug produced a
`response rate that hovers around 70%.
`
`Regarding safety, Dr. Chandler points out that higher-dose bromfenac studied in more than
`1,600 patients did not result in any serious corneal adverse events; ocular adverse events
`observed in these studies resolved with no sequelae. From the perspective of global clinical
`experience with bromfenac, in about 19 million ophthalmic uses of the currently marketed
`higher concentration, there have been 22 serious corneal adverse events reported overall.
`Not all were considered drug related, Dr. Chandler points out, and most were in subjects
`who had undergone cataract surgery. "Lowering the concentration of bromfenac as we have
`done could further reduce the likelihood of severe corneal adverse events," he says. As part
`
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`Ophthalmology Management
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`of its commitment to patient safety, Ista has incorporated frequent monitoring of the cornea
`into the protocols for the large safety trials being planned.
`
`0 SAR 1118. Sarcode Corp. says that the phase 2 results for SAR-118, a topical small-
`molecule lymphocyte function—associated antigen-1 antagonist, showed clear improvements
`in signs and symptoms of dry eye at 12 weeks. The trial was a randomized, multisite,
`doublemasked study involving 230 subjects. Various dose levels (0.1, 1.0 and 5.0%) were
`compared to placebo, with subjects receiving the drops BID for 12 weeks. The primary
`objective measure was inferior corneal staining; major secondary measures were OSDI
`symptom score and tear production by Schirmer test. The company will present full details
`of the phase 2 study in spring 2011. Sarcode is currently preparing for a phase 3 trial to
`begin in mid-2011.
`
`0 Mapracorat. Bausch + Lomb is addressing the issue of tear hyperosmolarity in dry eye
`disease, which research suggests is a mechanism involved in ocular surface inflammation,
`with its selective glucocorticoid receptor agonist (mapracorat), currently in phase 2 trials. In
`vitro studies suggest mapracorat inhibits hyperosmolar-induced cytokine release and
`mitogenactivated protein kinase pathways in human corneal epithelial cells. Development of
`the compound continues to progress as a novel product with a new mechanism of action for
`the treatment of dry eye, according to B+L.
`
`A study in the September 2010 issue of Molecular Vision showed it to have comparable
`activity to dexamethasone in combating inflammation. The investigators evaluated
`mapracorat's anti—inflammatory effects in an in vitro osmotic stress model that induced
`hyperosmolar conditions in cultured human corneal cells. The model stimulated the release
`of pro—inflammatory cytokines interleukin—6, interleukin—8 and monocyte chemotactic
`protein-1, and also altered the phosphorylation state of p38 and c—Jun N-terminal kinase
`(JNK), and the transcriptional activity of NFkappaB and AP—1. The researchers found that
`the incubation of cells with mapracorat inhibited hyperosmolarinduced cytokine release with
`potency comparable to the dexamethasone control group. Additionally, increased
`phosphorylation of p38 and JNK caused by hyperosmolarity was inhibited by mapracorat,
`and the compound caused a significant decrease in the hyperosmolar-induced rise in
`NFkappaB and AP-1 transcriptional activity.
`
`0 RX-10045. One of a class of medicines called resolvins, RX-10045 is a small-molecule
`lipid mediator that Resolvyx Pharmaceuticals says activates the body's own mechanisms for
`shutting off inflammation. It is administered as a topical eye drop. Resolvyx completed a
`phase 2 trial last year for chronic dry eye. In the randomized, placebo—controlled, 232-
`patient trial, RX-10045 produced dose-dependent, statistically significant improvement on
`the primary endpoints for both the signs and symptoms of dry eye, and was generally
`shown to be safe and well tolerated, the company says.
`
`The phase 2 study examined three doses of RX-10045 and used a controlled adverse
`environment (CAE) simulator to measure corneal staining in a stressful drying environment,
`as well as daily patient diaries using a standard visual analog scale to assess symptom
`improvement over the course of the 28-day study. The drug produced a significant
`dosedependent improvement from baseline in symptoms recorded in daily patient diaries. It
`also reduced staining of the central cornea by 75% (P<0.00001) versus placebo, the
`difference approaching statistical significance (P=0.11). Additionally, the drug showed a
`significant improvement in CAE-induced staining in the inferior cornea and in the composite
`of central and inferior cornea, which also approached statistical significance over placebo
`(P=0.09).
`
`Resolvyx says the phase 3 trial should begin by the end of the year.
`
`0 Azasite. Currently there is no prescription product indicated for blepharitis, a void Inspire
`Pharmaceuticals would like to fill with AzaSite (azithromycin). The drug is already approved
`as a treatment for bacterial conjunctivitis, but it did not meet statistically significant
`endpoints in two phase 2 trials for anterior blepharitis last spring. Though a four—week trial
`did demonstrate improvement in measured signs and symptoms compared to placebo,
`statistical significance was not achieved for the primary endpoint of mean lid margin
`hyperemia.
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`On the secondary endpoints, however, Inspire president and chief executive officer Adrian
`Adams reports seeing some statistical significance in the areas of signs and symptoms. In
`the two—week trial, there were no statistically significant improvements for AzaSite
`compared to vehicle; this included the primary endpoint of clearing of lid debris.
`
`The company says it will use the data obtained from these studies to continue to develop
`trial parameters using Azasite as a treatment for both anterior and posterior blepharitis,
`and expects to refine the trial design through the end of this year. The refinement will
`include study populations and "seeking improved mappability for assessing and measuring
`signs and symptoms," says Mr. Adams. "With that, we are looking to utilize the
`photographic reading centers to maximize the trial."
`'
`
`Inspire anticipates completing the additional phase 2 Azasite clinical work in 2011. The
`initiation of the phase 3 trial should begin sometime later next year.
`
`0 LX—214. Lux Biosciences' dose-ascending phase 1 trial showed that LX-214, a novel
`topical formulation of voclosporin, was well tolerated by healthy volunteers. There was no
`difference in tolerability between the vehicle control and the concentrations of drug tested
`(0.2% and 0.02%). In five subjects diagnosed with dry eye syndrome, the cohort "showed
`some improvement in their signs (measured by Schirmer‘s tear test) and symptoms
`(measured by the OSDI); most notably, the changes observed occurred in the relatively
`brief timeframe of the study, two weeks compared to what has been reported previously
`with cyclosporine emulsion," according to Dr. Anglade.
`
`Voclosporin affects the immune response at the surface of the eye, he explains. "We think
`by controlling the local inflam matory response, it will allow the tear-producing lacrimal
`gland and the surface of the eye to heal and improve tear production.
`
`LX—214 belongs to a class of agents known as calcineurin phosphatase inhibitors, developed
`by the company into a nanomicellar formulation. "This renders LX214, a highly insoluble
`compound, a solution as opposed to an emulsion," Dr. Anglade explains. He believes the
`drug's solution formulation will help make it better tolerated than cyclosporine emulsion.
`
`Another advantage, says Dr. Anglade, is voclosporin's higher concentration. "A limitation of
`other forms of topical cyclosporine is that sufficiently high concentrations may not be
`achieved locally. The ability to achieve high local concentrations may translate into
`improved efficacy. We'll be able to assess that concept hopefully in the phase 3 when we do
`a large dose-ranging study."
`
`Dr. Anglade adds that the company is planning a phase 2 proof-of-concept study for the
`near future.
`
`0 Restasis X. Allergan reports that it is currently testing a new variation of cyclosporine,
`Restasis X, in phase 2 clinical trials. The company is not able to speculate on expected
`timing for FDA approval.
`
`In related news, in a study published in the August issue of the British Journal of
`Ophthalmology, researchers evaluated the efficacy and safety of two concentrations (0.05%
`and 0.1%) of cyclosporine A in aqueous solution compared to vehicle in treating the signs
`and symptoms of moderate-tosevere dry eye patients.‘ At Day 21, the 1°/o group showed
`statistically significant improvement (p<0.05) in four symptoms and three ocular signs; the
`0.05% showed statistically significant improvement in three symptoms and three signs; and
`the vehicle—only group in two symptoms and two signs. According to the researchers, at Day
`42, the 0.1% group performed demonstrated improvement in four symptoms, while the
`0.05% group demonstrated improvement in one symptom and one sign.
`
`Hope for The Future
`
`Dr. Lemp’s vantage point as a participant in many FDA trials gives him reason to believe
`that the regulatory situation for dry eye drugs will soon improve. "As we learn more about
`the pathological processes at work in dry eye disease, new treatment strategies are
`emerging and data to support new endpoints are being published," he notes.
`
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`Ophthalmology Management
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`For one thing, in a meeting earlier this year, the FDA‘s Wiley Chambers, MD, expanded the
`criteria for primary endpoints that the agency will accept, including studies that document a
`correlation between signs and symptoms. Included in that slide was a list of inflammatory
`cytokines in the tears and tear osmolarity. "That's new," says Dr. Lemp. "That's potentially
`big."
`
`Patient-reported outcomes are gaining favor with the FDA as well. The most common
`vehicle for reporting patient symptoms has been the 100-point scale OSDI. However,
`showing the required 29-point improvement in symptoms has been onerous. It has required
`sponsors to find patients who were highly symptomatic —— "Who at least start out with 50 to
`60 points on the scale," Dr. Lemp says. "And that rules out 90% of the population with dry
`eye."
`
`New studies re—examining the relationships between subjective patient changes and levels
`of disease severity, novel ways to assess patient-reported improvement and a better
`understanding of the relationship between signs and symptoms in dry eye disease all have
`the potential to open the door to less onerous but scientifically rigorous study designs, Dr.
`Lemp notes. He believes that this augurs well for demonstration of clinical efficacy and the
`appearance of an expanded therapeutic portfolio of drugs for the more effective
`management of dry eye disease.
`
`Perhaps the best reason to believe that the fortunes of prescription dry eye drugs will
`improve? "Let's put it this way, to my knowledge, there are probably more than 30 drugs in
`the pipeline," says Dr. Lemp. Many companies are investing in the dry eye market, and not
`just "the usual suspects" such as Alcon, Allergan and B+L.
`
`The fact that Restasis could generate an approximate half a billion dollars in revenue last
`year despite its demonstrated effect in only about 15% of the patients studied (according to
`the package label), indicates significant unmet medical need and a healthy bottom line for
`those willing to invest.
`
`with industry on board and the FDA willing to update its clinical trial criteria, the conditions
`for victories seem to be increasingly in place. OM
`
`Reference
`
`1. Baiza—Durén L, Medrano—Palafox J, Hernéndez—Quintela E, Lozano—A|cazar J, Alaniz-de la
`0 JF. A comparative clinical trial of the efficacy of two different aqueous solutions of
`cyclosporine for the treatment of moderate—to—severe dry eye syndrome. Br] Ophthalmol.
`2010 Aug 1. [Epub ahead of print]
`
`
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`Clinical Trial Pearls
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`0422
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`Ora, Inc. has been helping drug makers navigate clinical trials for 15 years, says George
`Ousler, director of the company's dry eye department, so they have a lot of experience in
`knowing what makes for a successful program. Here are his recommendations:
`0 Identify proper inclusion/exclusion criteria. Because there are many different
`causes of dry eye, and different medications that could potentially treat it, it is critical that
`companies take the time to match the medication's mechanism of action to the
`appropriate patient population.
`0 Focus on both signs and symptoms. Related to proper inclusion criteria, it is
`necessary to only include patients who show both signs and symptoms of dry eye. "It
`sounds pretty straightforward, but there's actually a fair amount of lack of correlation
`between the two," Mr. Ousler says.
`0 Design well-controlled studies and standardize. Certain clinical models enable
`better control for the endpoints of dry eye. Toward this end, Ora has developed the
`Controlled Adverse Environment (CAE). By controlling environmental factors such as
`humidity, temperature, air flow and visual tasking, "you can establish a screening tool to
`identify the right patient, and an endpoint to demonstrate efficacy. If it's better controlled,
`there's not so much background noise like traditional environmental studies," Mr. Ousler
`explains.
`'
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`e Refiuce ciinicefl sites. This heips to keep the triai weii contreiied and standardized.
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`E athwaa " Mr Ousier
`................................. , ..
`
`
`
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`Ophthameiagy Management, Issue: November 2010
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`0423
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`0426
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`Inspire shelves dry-eye drug, shifts focus with Allergan - Triangle Business Journal
`
`Page 1 of 2
`
`From the Triangle Business Journal
`:http: / /www.bizjournals.com/triangle/stories/ 2010/ 08/ 23/daily31.html
`
`Aug 25, 2010, 12:52pm EDT
`
`Inspire shelves dry-eye drug, shifts
`focus with Allergan
`
`Jeff Drew
`
`After a decade of development and disappointment, Inspire Pharmaceuticals finally has put
`a stop to its efforts to win U.S. Food and Drug Administration approval of a dry eye drug
`now called Prolacria.
`
`The Durham company on Wednesday unveiled a modified collaboration agreement with
`longtime partner Allergan (NYSE: AGN) that opens the way for Inspire to close the door on
`Prolacria and move its focus to pink eye treatment AzaSite and the gggggggagg;«:j§,§;:g,{33j§jg1g
`
`Investors hailed the new agreement, pushing up Inspire shares by 3.88 percent, to $4.66, in
`mid-day trading Wednesday.
`
`Inspire twice saw its dry eye drug fail to outperform a placebo in the last stage of human
`testing. The company tried changing the drug's name and adjusted the end point of the
`phase III clinical trial but gnngiedigfluggwjtgumtlgemsawmgeggesggztg.
`
`After studying the potential of moving forward with Prolacria, Inspire and Allergan were
`ready to move on. But the complicated nature of their drug development deal — which
`involves another dry eye treatment, Restasis — left Inspire facing a significant and
`immediate revenue hit.
`
`Inspire (Nasdaq; ISPH) receives royalties from Allergan on sales of Restasis and received
`payments from the Irish company for hitting development milestones on Prolacria. The
`previous terms called for a 30 percent reduction in Inspire’s Restasis royalty rate of 7.5
`percent if the company dropped the Prolacria program and didn't begin contributing to the
`marketing and promotion of Restasis.
`
`The new terms keep Inspire’s Restasis royalty rate unchanged at 7.5 percent for 2010,
`before reducing it by 3 percentage points in 2011, a further 0.25 percentage point in 2013,
`and a final 0.50 percentage point in 2014. The rate will remain at 3.75 percent until 2020,
`when the contract runs out.
`
`Restasis generated $11.2 million in royalty revenue for Inspire during the second quarter,
`which ended June 30. That was up from $8.9 million in the year-ago quarter.
`
`0427
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`
`Inspire shelves dry-«eye drug, shifts feeus with Ailergan — Triangle Business Jeurnai
`
`Page 2 of 2
`
`For the quarter, Restasis accounted fer mere than 46 percent at Inspires total revenue of
`$27.3 miiiien and tapped AzaSite, which produced revenue of $9.6 miiiien.
`
`“This agreement provides ciarity en the revenue stream and respective respensibiiities of the
`parties in our ephthairnic coiiaberatipn,” said Adrian Adams, president and CEQ pf Inspire,
`which has 243 empioyees.
`
`Reporter e-maii: jdrew@hizjournais.com
`
`0428
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`Electronic Acknowledgement Receipt
`
`17119376
`
`Application Number:
`
`13967168
`
`International Application Number:
`
`Confirmation Number:
`
`Title of Invention:
`
`METHODS OF PROVIDING THERAPEUTIC EFFECTS USING CYCLOSPORIN
`COMPONENTS
`
`First Named Inventor/Applicant Name:
`
`Andrew Acheampong
`
`Customer Number:
`
`51957
`
`Laura Lee Wine/Alexis Swan
`
`Filer Authorized By:
`
`Laura Lee Wine
`
`Attorney Docket Number:
`
`17618CON7B (AP)
`
`Receipt Date:
`
`14—OCT—201 3
`
`Filing Date:
`
`14-AUG-2013
`
`Time Stamp:
`
`16:25:48
`
`Application Type:
`
`Utility under 35 USC111(a)
`
`Payment information:
`
`Submitted with Payment
`
`File Listing:
`
`Document
`Number
`
`Document Description
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`(if appl.)
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`17618CON7B-Response-to-
`NFOA.pdf
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`Multi
`
`Part /.zip
`
`Pages
`
`File Size(Bytes)/
`Message Digest
`1536018
`
`9679d4362e0626801a97904f2695f356bc0
`7a5dd
`
`0429
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`Multipart Description/PDF files in .zip description
`
`.
`.
`_
`_
`_
`Affidavit-traversing rejectns or objectns
`ru1e132
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`17618CON7B-Exhibit-1.pdf
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`a200ddb77f2832f7af94e1a8faf579658491 ‘
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`Affidavit-traversing rejectns or objectns
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`Affidavit-traversing rejectns or objectns
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`
`73f37Cd3b7dd18045796bad606229a8be6 =
`24edd
`
`7072017
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`The page size in the PDF is too large. The pages should be 8.5 x 11 or A4. If this PDF is submitted,the pages will be resized upon entry into the
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`PTO/SB/06 (09-11)
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`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
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`Application or Docket Number
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`08/14/2013 D To be Mailed
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`PATENT APPLICATION FEE DETERMINATION RECORD
`Substitute for Form PTO-875
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`ENTITY:
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`IZI LARGE |:| SMALL |:| MICRO
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`APPLICATION AS FILED — PART I
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`(Column 2)
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`FOR
`
`NUMBER FILED
`
`NUMBER EXTRA
`
`I:I BASIC FEE
`37CFR1.16a, b,or c
`
`El SEARCH FEE
`37CFR1.16k,
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`i,or m
`
`D EXAMINATION FEE
`(37 CFR1.16( ), (p), or (q))
`TOTAL CLAIMS
`37 CFR 1.16 i
`INDEPENDENT CLAIMS
`37 CFR1.16 h
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`DAPPLICATION SIZE FEE
`(37 CFR1.16(s))
`
`N/A
`
`N/A
`
`N/A
`
`N/A
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`N/A
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`minus 20 =
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`minus3=
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`* If the difference in column 1 is less than zero, enter “0" in column 2.
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`APPLICATION AS AMENDED — PART II
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`P RESENT EXTRA
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`ADDITIONAL FEE ($)
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`1o/14/2013
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`Total (37 CFR
`
`Independent
`37CFR1.16h
`
`CLAIMS
`
`f,‘E$”E’*,',N'NG
`AMENDMENT
`,
`
`HIGHEST
`NUMBER
`PREVIOUSLY
`PAID FOR
`,,
`
`24
`“*3
`
`-
`Mm
`-
`Mmus
`
`I:I Application Size Fee (37 CFR1.16(s))
`
`D FIRST PRESENTATION OF MULTIPLE DEPENDENT CLAIM (37 CFR1.16(j))
`
`AMENDMENT
`
`AMENDMENT
`
`CLAIMS
`REMAINING
`AFTER
`AMENDMENT
`~k~k
`-
`*
`I
`T I
`2 Mm -
`Minus
`(37 CFR1.16(h))
`
`HIGHEST
`NUMBER
`PREVIOUSLY
`PAID FOR
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`I:I Application Size Fee (37 CFR1.16(s))
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`D FIRST PRESENTATION OF MULTIPLE DEPENDENT CLAIM (37 CFR1.16(j))
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`P RESENT EXTRA
`
`ADDITIONAL FEE (515)
`
`II
`
`>< %CD 0
`
`TOTAL ADD‘L FEE
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`X %
`>< %
`
`ll
`
`TOTAL ADD‘L FEE
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`* If the entry in column 1 is less than the entry in column 2, write “0" in column 3.
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`Docket No. 17618CON7B (AP)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant: Acheampong, et al.
`
`Examiner: Marcela M Cordero Garcia
`
`Serial No.: 13/967,168
`
`Group Art Unit: 1658
`
`Filed: August 14, 2013
`
`Confirmation No. 3265
`
`For: METHODS OF PROVIDING
`
`Customer No.: 51957
`
`THERAPEUTIC EFFECTS USING
`
`CYCLOSPORIN COMPONENTS
`
`INTERVIEW SUMMARY
`
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Dear Sir:
`
`Attached herewith please find an interview summary.
`
`Summary of the Interview begins at page 2.
`
`0433
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`

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`Docket No. 17618CON7B (AP)
`
`SUMMARY OF INTERVIEW
`
`Attendees, Date and Type of Interview
`
`A telephone interview was conducted on November 7, 2013 and was attended by
`
`Examiner Cord