Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 1 of 27 PageID #: 346
`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 1 of 27 PageID #: 346
`
`EXHIBIT A
`
`EXHIBIT A
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 2 of 27 PageID #: 347
`PAUL
`HASTINGS
`
`1(202) 551-1990
`naveenmodi@paulhastings.com
`
`July 7, 2017
`
`Matthew B. Lowrie
`Foley & Lardner LLP
`111 Huntington Avenue
`Suite 2600
`Boston, MA 02199
`
`Re:
`
`Univ. of Mass. Med. School and Carmel Labs., LLC v. L'Oreal S.A.
`and L'Oreal USA, Inc. , 1:17-cv-08868-UNA (D. Del.)
`
`Dear Matt:
`
`We have been engaged by L'Oreal USA, Inc. for the above-referenced matter. We have reviewed the
`Complaint filed in this matter, alleging infringement of U.S. Patent Nos. 6,423,327 (the "' 327 patent") and
`6,645,513 (the '"513 patent"). We have some serious concerns regarding the propriety of the Complaint.
`
`As you are aware, Rule 8 requires "a short and plain statement of [each] claim showing that the pleader is
`entitled to relief." Fed. R. Civ. P. 8(a)(2). This standard "demands more than an unadorned, the(cid:173)
`defendant-unlawfully-harmed-me accusation. " Ashcroft v. Iqbal, 556 U.S. 662, 678 (2009). Complaints
`must allege sufficient facts to "raise a right to relief above the speculative level .... " Bell At/. Corp. v.
`Twombly, 550 U.S. 544, 555 (2007). Plaintiffs have not met their pleading burden.
`
`For example, as set forth at 1f12, the Complaint admits that claim 1 of both of the '327 and '513 patents
`re3,uires that the "adenosine concentration applied to the dermal cells is 10-4 M to 10-7 M," and "10-3 M to
`1 o- M," respectively. As an initial matter, although the Complaint identified numerous brands "with
`products containing adenosine," only one product (L'Oreal Paris' Revitalift Triple Power Deep-Acting
`Moisturizer) is identified as an "Accused Adenosine Product." Complaint, 1Ji131, 34. However, nowhere in
`the Complaint do Plaintiffs even attempt to al lege that this sole Accused Adenosine Product meets the
`adenosine concentration claim requirement for either the '327 or '513 patents. Indeed, there is no
`assertion regarding the amount of adenosine in the sole Accused Adenosine Product, or any product of
`the identified brands. As such, the Complaint fails, on its face, to meet the proper pleading standard of
`Rule 8.
`
`You are aware that the pre-suit investigation mandated by Rule 11 requires a review of all relevant
`materials, including the prosecution history of the asserted patents. See, e.g., Vehicle Operation Techs.
`LLC v. Am. Honda Motor Co., 67 F. Supp. 3d 637 (D. Del. Sept. 12, 2014). In order to overcome a prior
`art rejection during prosecution of the '327 patent (to which the '513 patent also claims priority),
`Applicants distinguished over a composition containing an adenosine concentration of 0.033% (i.e., one
`third of 0.1 %). See, e.g., Amendment mailed February 11, 2002 ("Amendment"), and accompanying
`Declaration Under 37 C.F.R. § 1.132 ("Declaration") in U.S. Patent Application No. 09/672,348. As such,
`Plaintiffs cannot now try to cover any method using a composition containing an adenosine concentration
`greater than required by the claims of the '327 and '513 patents. In this regard , we presume that the only
`Accused Adenosine Product identified in the Complaint, L'Oreal Paris' Revitalift Triple Power Deep(cid:173)
`Acting Moisturizer, was appropriately analyzed in Plaintiffs' pre-suit investigation required by Rule 11 .
`Such testing would have shown that the amount of adenosine present in this lone Accused Adenosine
`Product falls outside the claimed range of both the '327 or the '513 patents. Thus, Plaintiff's identification
`
`Paul Hastings LLP I 875 15th Street, N .W. I Washington, DC 20005
`t: +1.202.551.1700 I www.paulhastings.com
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 3 of 27 PageID #: 348
`PAUL
`HAST I NGS
`
`Matthew B. Lowrie
`July?, 2017
`Page 2
`
`of L'Oreal Paris' Revitalift Triple Power Deep-Acting Moisturizer as the single Accused Adenosine
`Product fails to satisfy Plaintiffs' burden under either Rules 8 or 11 .
`
`We understand that, over the past two years , Plaintiffs have been repeatedly asked for identification of
`allegedly infringing products and the basis for any possible claim of infringement (e.g., testing results
`demonstrating that use of any product falls within the scope of the claims). Because this information was
`not provided despite repeated requests, and is notably absent from the Complaint, we are left to conclude
`that there is no reasonable basis for the accusation of infringement in the Complaint.
`
`In view of the foregoing, we ask that Plaintiffs immediately provide an adequate basis for the Complaint or
`dismiss their Complaint. If Plaintiffs fail to do so by July 14, 2017, we reserve the right to seek appropriate
`relief from the Court, including but not limited to a request for dismissal with prejudice, attorney fees, and
`costs.
`
`Since~ J~ A.
`
`Nave en Modi
`Global Vice Chair of IP
`
`cc: Brian E. Farnan
`Michael J. Farnan
`William Christopher Carmody
`Tamar E. Lusztig
`Justin A. Nelson
`Matthew A. Ambros
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 4 of 27 PageID #: 349
`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 4 of 27 PageID #: 349
`
`EXHIBIT B
`
`EXHIBIT B
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 5 of 27 PageID #: 350
`
`Ashraf, Amina
`
`From:
`Sent:
`To:
`Cc:
`
`Subject:
`
`Justin A. Nelson <jnelson@SusmanGodfrey.com>
`Monday, July 10, 2017 5:25 PM
`Ashraf, Amina; mlowrie@foley.com; Modi, Naveen
`bfarnan@farnanlaw.com; mfarnan@farnanlaw.com; Bill Carmody; Tamar Lusztig;
`mambros@foley.com
`RE: Univ. of Mass. Med. School and Carmel Labs., LLC v. L’Oréal S.A. and L’Oréal USA,
`Inc.
`
`Dear Naveen:
`
`Thank you for your letter of July 7, 2017. It is an inauspicious way to start a dialogue with
`opposing counsel by insinuating a Rule 11 violation. Rest assured, our firms have conducted a
`good faith investigation that more than satisfies Rule 11. Our experience is that further letter-
`writing campaigns on this point make little sense. We strongly disagree that we have somehow
`failed to adequately plead infringement. If, however, you believe in good faith that we have not
`adequately pleaded something, then make your motion. We look forward to interacting with
`you in a cooperative and friendly manner.
`
`On a separate note, can you please let us know whether you will accept service on behalf of
`L’Oreal S.A.? Should you accept, we will of course be amenable to a reasonable extension for
`you to file your responsive pleading on behalf of both defendants. I have included only you and
`Amina Ashraf on this email but please let us know whether we should include others from your
`firm or prior settlement counsel.
`
`Regards,
`
`Justin
`
`
`From: Ashraf, Amina [mailto:aminaashraf@paulhastings.com]
`Sent: Friday, July 07, 2017 2:25 PM
`To: mlowrie@foley.com
`Cc: bfarnan@farnanlaw.com; mfarnan@farnanlaw.com; Bill Carmody; Tamar Lusztig; Justin A. Nelson;
`mambros@foley.com
`Subject: Univ. of Mass. Med. School and Carmel Labs., LLC v. L’Oréal S.A. and L’Oréal USA, Inc.
` 
`Counsel,  
` 
`Please see the attached.  
` 
`Regards,  
`Amina Ashraf  
`
`____________________________________________________________________________ 
`1
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 6 of 27 PageID #: 351
`
`Amina Ashraf | Client Service Specialist
`Paul Hastings LLP | 875 15th Street, N.W., Washington, DC 20005 | Direct:
`+1.202.551.1230 | Main: +1.202.551.1700 | Fax: +1.202.551.0130 |
`AminaAshraf@PaulHastings.com | www.paulhastings.com  
`
` 
`
` 
`  
` 
` 
`
`******************************************************************************************
`This message is sent by a law firm and may contain information that is privileged or confidential. If you received
`this transmission in error, please notify the sender by reply e-mail and delete the message and any attachments.
`
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`
`2
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 7 of 27 PageID #: 352
`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 7 of 27 PageID #: 352
`
`EXHIBIT C
`
`EXHIBIT C
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 8 of 27 PageID #: 353
`
`International Journal of Cosmetic Science, 2006, 28, 447–451
`
`Evaluation of anti-wrinkle efficacy of adenosine-
`containing products using the FOITS technique
`
`M.L. Abella
`L’Ore´al Recherche, 188 rue Paul Hochart, 94152 Chevilly-Larue Cedex, France
`
`Received 1 April 2006, Accepted 15 August 2006
`
`Keywords: adenosine, facial wrinkles, fast optical in vivo topometry of human skin
`
`Synopsis
`
`Re´ sume´
`
`The objective of this study was to evaluate formu-
`lations containing adenosine to reduce periorbital
`lines and glabellar frowns in a blind, randomised,
`placebo-controlled study. One hundred twenty-six
`female volunteers between 45 and 65 years of age
`fulfilled inclusion criteria for periorbital lines. They
`were provided with two of three products (cream
`with adenosine, dissolvable film with adenosine or
`placebo), to be applied to the periorbital area on
`each side of the face (84 subjects per product).
`Eighty-four of these subjects also fulfilled the inclu-
`sion criteria for glabellar frowns, and received pla-
`cebo or cream with adenosine to be applied to the
`glabellar area. Products were applied twice daily
`for 2 months, and evaluation was performed
`under dermatological supervision at 0, 3 and
`8 weeks using Fast Optical
`in vivo Topometry of
`human Skin (FOITS) analysis to describe skin pro-
`file. Both adenosine-containing products led to sig-
`nificant improvements in skin smoothness in the
`periorbital area.
`Improvements were evidenced
`after 3 weeks of product application as measured
`by Ra and Rz parameters using the FOITS tech-
`nique, and were steadily confirmed after 2 months,
`despite severe climatic conditions and independ-
`ently of the analysis technique that was used with
`the FOITS data. Adenosine-containing cream also
`significantly improved glabellar frowns. This study
`demonstrates
`the potential beneficial effects of
`adenosine-containing products on crow’s feet and
`glabellar facial wrinkles.
`
`Correspondence: M.L. Abella, L’Ore´al Recherche, 188 rue
`Paul Hochart, 94152 Chevilly-Larue Cedex, France. Tel.:
`+33 (1) 49 79 55 21; e mail: mlabella@rd.loreal.com
`
`Le but de cette e´tude est d’e´valuer dans une e´tude
`randomise´e controle´e contre placebo des formules
`contenant l’ade´nosine pour re´duire les rides pe´rior-
`bitales et les sillons glabellaires. 126 femmes de 45
`a` 65 ans re´pondant aux crite`res d’inclusion pour
`les rides pe´riorbitales ont rec¸u 2 des 3 produits e´tu-
`die´s (cre`me a` l’ade´nosine, film solubilisable a` l’ade´-
`nosine ou placebo) pour application sur la zone
`pe´riorbitale de chaque cote´ du visage (84 sujets par
`produit). 84 de ces sujets remplissaient e´galement
`les crite`res d’inclusion pour les sillons glabellaires,
`et ont rec¸u soit la cre`me a` l’ade´nosine soit le pla-
`cebo pour application sur la zone glabellaire. Appli-
`cation des produits 2 fois par jour pendant 2 mois,
`et e´valuation sous controˆle dermatologique a` 0, 3
`et 8 semaines a` l’aide de la me´thode FOITS ( Fast
`Optical in vivo Topometry of human Skin) d’analyse
`du profil cutane´. Les deux produits contenant l’ade´-
`nosine ont conduit a` une ame´lioration significative
`du relief cutane´ de la zone pe´riorbitale. L’ame´liora-
`tion est mesure´e de`s 3 semaines pour les para-
`me`tres Ra et Rz de la me´thode FOITS, et se
`maintient apre`s 2 mois, malgre´ des conditions cli-
`matiques se´ve`res. La cre`me contenant l’ade´nosine a
`e´galement ame´liore´ de fac¸on significative les sillons
`glabellaires. Cette e´tude met en e´vidence les effets
`be´ne´fiques potentiels des produits contenant l’ade´-
`nosine sur les rides de la patte d’oie et de la glabelle.
`
`Introduction
`
`Wrinkle development, as a direct consequence of
`skin ageing, has important social and psychologi-
`cal impacts which have become exaggerated with
`
`ª 2006 L’Ore´al. Journal compilation
`ª 2006 Society of Cosmetic Scientists and the Socie´te´ Franc¸aise de Cosme´tologie
`
`447
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 9 of 27 PageID #: 354
`
`Evaluation of anti-wrinkle efficacy of adenosine-containing products
`
`M.L. Abella
`
`longer life expectancy and changing social values.
`The skin ageing process can be separated into two
`simultaneous processes – chronological (or intrin-
`sic) ageing and extrinsic ageing (induced by cumu-
`lative
`exposures
`to
`environmental
`factors,
`especially UV light).
`Wrinkle development in intrinsically aged skin
`has been associated with decreased elastin [1] and
`laminin 5 [2],
`leading to the breakdown of the
`extracellular matrix and in particular disruption
`and flattening of the dermal–epidermal
`junction.
`This degradation of elastic fibres constituting the
`elastin network, in conjunction with marked colla-
`gen reduction, appears to be a major culprit in
`wrinkle formation, as it reduces the capacity of
`aged skin to resist gravitational effects and return
`to its native state after expressional changes.
`While expression lines such as periorbital wrinkles
`and glabellar frowns can be perceived as manifes-
`tations of personality, they are nevertheless early
`indicators of the future of the face, and will inevit-
`ably develop into ageing related wrinkles. These
`‘dynamic’ wrinkles are perpendicular to the direc-
`tion of the underlying facial muscles. Tensile forces
`are generated by these muscles and with time and
`repetition they can eventually lead to modifica-
`tions of the contractile properties of fibroblasts.
`The demonstration nearly 20 years ago in a
`controlled study that
`topical
`tretinoin could
`reduce both fine and coarse wrinkles in photo-
`aged skin [3], provided the impetus for consider-
`able research into the possibility of cosmetic
`correction of skin ageing. Products developed to
`date range from basic moisturisers (which offer
`only transient rehydrating effects on wrinkles) to
`sophisticated cosmetic formulations which exert a
`much more complex activity by protecting the
`skin from further damage, nourishing it, stimula-
`ting renewal of superficial layers, or even restor-
`ing skin structure, and contain functional agents
`with reported beneficial effects including vitamins,
`retinoids, hydroxy acids, fish and plant polysac-
`charides, enzyme inhibitors or antioxidant modu-
`lators [4].
`In this respect, products containing
`agents such as adenosine which have been elab-
`orated to limit the calcium-induced cellular con-
`tractions, are worthy of study for their possible
`beneficial
`effects on ‘dynamic’ wrinkles. This
`paper presents the results of a placebo-controlled
`study on the effects of cosmetic preparations con-
`taining adenosine to reduce crow’s feet and gla-
`bellar facial wrinkles.
`
`Subjects and methods
`
`feature of this study is its double
`The original
`design. Two different methodologies have been
`used on the same subject, an incomplete block
`design on the crow’s feet area and a parallel
`design on the glabellar area.
`A placebo cream known from previous studies
`to have no effect on wrinkles was used as control.
`
`Periorbital lines
`
`Inclusion criteria
`One hundred twenty-six women, aged between
`45 and 65 years and with wrinkles greater than
`2 cm in length without criss-crossing lines were
`enrolled. Wrinkle characteristics for inclusion in
`the study were assessed according to the L’Oreal
`crow’s feet wrinkle photographic Chart, and cri-
`teria for inclusion was set as follows: wrinkles
`graded greater
`than 4 (if only one wrinkle),
`greater than depth grade 3 (for two wrinkles) or
`greater than depth grade 2 (for three or four
`wrinkles).
`
`Methodology
`The study was carried out as an incomplete block
`design where not every subject got all treatments.
`According to randomization, subjects were given
`two of three blinded products – (C) cream with
`0.1% adenosine,
`(A) dissolvable film with 1%
`adenosine or (B) placebo cream (without adeno-
`sine), and requested to apply one product on the
`right crow’s feet only and the other one on the left
`crow’s feet only. Each product was used 84 times
`and all three combinations (A vs. B, C vs. A and B
`vs. C) 42 times.
`
`Glabellar frowns
`
`Inclusion criteria
`Eighty-four of the 126 total subjects also fulfilled
`criteria for inclusion in the glabellar frown arm of
`this study: glabellar frowns were assessed accord-
`ing to a photographic scoring method (L’Ore´al gla-
`bellar wrinkles Chart) in the same way as for the
`periorbital wrinkles.
`
`Methodology
`The study was carried out as a parallel group
`design. Subjects were divided into two groups of
`42 each and given one of two blinded products (C)
`
`448
`
`ª 2006 L’Ore´al. Journal compilation
`ª 2006 Society of Cosmetic Scientists and the Socie´te´ Franc¸aise de Cosme´tologie, 28, 447–451
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 10 of 27 PageID #: 355
`
`Evaluation of anti-wrinkle efficacy of adenosine-containing products
`
`M.L. Abella
`
`cream or (B) placebo, to be applied to the glabellar
`area. Product A was not used on this location.
`
`Exclusion criteria
`
`sign an
`Subjects who did not or could not
`informed consent form, those unable to comply
`with the requirements of the protocol and those
`who were participating in any other clinical study
`were excluded.
`
`Test substance application protocol
`
`The study took place between mid September and
`mid December in the central part of Germany.
`Application of any cosmetic products was prohi-
`bited 3 days prior to the start of the study. During
`the study,
`facial cleansing was allowed in the
`morning using pure water, and in the evening
`using only the cleansing milk provided. Subjects
`were instructed to apply the test product twice
`daily (once in the morning, once in the evening).
`For periorbital
`lines, the right hand index was
`used to apply one product to the left periorbital
`region, and the left hand index to apply the other
`product on the right periorbital region. For those
`subjects also enrolled in the glabellar frown study,
`test product (C or B) was applied after periorbital
`applications, using the right-hand middle finger.
`For both studies, cream (products C and B) was
`applied by gentle circular massaging motion, and
`for those subjects applying dissolvable film (prod-
`uct A), the treated area was first moistened, and
`the dissolvable film applied in a similar way by
`gentle circular massage.
`
`Assessment calendar, methodologies and statistical
`analyses
`
`The study protocol included evaluation at day 0,
`and after 3 and 8 weeks of treatment. Subjects
`were requested to apply test products at
`least
`12 h prior to assessment. Measurements of skin
`roughness were performed using the FOITS tech-
`nique [5, 6],
`followed by analysis of
`the skin
`profile with the ‘classical’ Din parameters method
`and by the Frequency of distribution of Heights
`method (FDH) which gives additional information
`on effects on wrinkles of different depth. Meas-
`urements were taken after an acclimatization
`period of 45 min in a strictly controlled environ-
`ment. Hygrometry
`and
`ambient
`temperature
`
`the study
`
`were recorded each day throughout
`period.
`FOITS classical analysis was used to record the
`two roughness parameters Ra (average roughness)
`and Rz (average of the heights measured between
`the peaks and troughs of each relief
`feature) as
`described previously [5]. FOITS is an optical meas-
`urement procedure which uses a combination of
`grey code and phase shift technique. The system
`comprises a projection unit and a CCD camera. As
`for PRIMOSÒ, both methods use fringe projection,
`they differ in the way stripes are generated on the
`skin. Ra and Rz were determined on 50 parallel
`lines perpendicular to the axis of the main wrinkle
`and starting from the corner of the eye (for perior-
`bital
`lines), adjacent
`lines being separated by
`250 lm.
`FDH measured the frequency of distribution of
`the heights
`in the field of
`[minus]600 to
`+600 lm with an interval step of 5 lm. So,
`three types of relief were evaluated according to
`(0–50 lm), fine
`time: micro-relief
`lines
`(55–
`110 lm) and coarse wrinkles (115–600 lm). As
`an average profile comprises approximately 65%
`micro-relief, 25% fine lines and only 10% coarse
`wrinkles, an increase in skin smoothness as
`detected by a reduction in coarse wrinkles will
`simultaneously affect fine lines or micro-relief.
`This additional analysis was performed for the
`periorbital area.
`For Ra and Rz parameters, the statistical signifi-
`cance of measured parameters was evaluated
`using the ANOVA test. Logarithms of the true Ra
`and Rz values were used as the values do not fol-
`low the law of normal distribution. For measure-
`ments which were statistically significant after
`variance analysis, three types of comparison were
`performed:
`initial vs. final value; and for the
`crow’s feet area study, comparison of effects of
`product C (cream) or A (dissolvable film) vs. pla-
`cebo (Dunnett test) and for the glabellar study,
`comparison of product C (cream) vs. placebo (Dun-
`nett test).
`For FDH measurements, Student’s t-tests were
`performed separately for each class of periorbital
`wrinkles. Climatic conditions can dramatically
`affect
`facial
`skin smoothness, and during the
`2 months duration of the study in the winter sea-
`son, climatic variations were unavoidable. To cor-
`rect
`for
`this effect,
`the values obtained with
`adenosine-containing products were corrected for
`the placebo values.
`
`ª 2006 L’Ore´al. Journal compilation
`ª 2006 Society of Cosmetic Scientists and the Socie´te´ Franc¸aise de Cosme´tologie, 28, 447–451
`
`449
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 11 of 27 PageID #: 356
`
`Evaluation of anti-wrinkle efficacy of adenosine-containing products
`
`M.L. Abella
`
`Cream C
`
`0
`
`3
`Week of study
`
`8
`
`(a)
`
`+5
`
`0
`
`–5
`
`–10
`
`–15
`
`–20
`
`after correction for placebo effects
`
`% Difference to baseline (T0)
`
`Film A
`
`3
`Week of study
`
`8
`
`+5
`
`0
`
`–5
`
`–10
`
`–15
`
`–20
`0
`
`after correction for placebo effects
`
`(b)
`
`% Difference to baseline (T0)
`
`Cream C
`
`3
`Week of study
`
`8
`
`Film A
`
`3
`
`Week of study
`
`8
`
`0
`
`–5
`
`correction for placebo
`
`(a)
`
`% Reduction in R value after
`
`–10
`
`0
`
`0
`
`–5
`
`correction for placebo
`
`(b)
`
`% Reduction in R value after
`
`–10
`
`0
`
`Figure 1 FOITS analysis of skin smoothness parameters
`in the periorbital region after application of cream C (a) or
`dissolvable film A (b) containing adenosine. The rough-
`ness parameters Rz and Ra were measured by FOITS tech-
`nique. R values are plotted as percentage reduction from
`baseline values at the start of the study after correction
`for evolution of values obtained with placebo, as a func-
`tion of time. Solid lines, Rz; dashed lines, Ra.
`
`Figure 2 FDH analysis of periorbital regions after appli-
`cation of cream C (a) or dissolvable film A (b) containing
`adenosine. FDH measurements of micro-relief (0–50 lm,
`dashed lines), fine wrinkles (55–110 lm, solid lines), and
`coarse wrinkles (115–600 lm, bold lines) are plotted
`against time, and expressed as per cent difference to
`baseline values after correction for values obtained with
`placebo.
`
`Results
`
`Periorbital lines
`
`All of the included 126 subjects completed this
`randomized trial. As measured by FOITS, both the
`Ra and Rz skin roughness parameters diminished
`dramatically following applications of both the C
`cream and A dissolvable film containing adenosine
`(Fig. 1a,b). Significant differences in evolution of
`skin smoothness were evidenced between both
`cream and film with adenosine and placebo at 3
`and 8 weeks (P £ 0.05 for both Ra and Rz, Tukey
`test). Similar results were obtained using the FDH
`method (Fig. 2). With both adenosine-containing
`
`products, C cream and A dissolvable film, signifi-
`cant improvements in skin smoothness were detec-
`ted as early as 3 weeks after the start of the study
`(as evidenced by a decrease in the frequency of
`coarse wrinkles and fine lines, with a corres-
`ponding increase in micro-relief) and were main-
`tained at week 8.
`
`Glabellar frowns
`
`All 84 subjects completed the study. As assessed
`by FOITS analysis, application of cream with
`adenosine (C) produced considerable reductions in
`both the Rz and Ra parameters in the glabellar
`region at 3 and 8 weeks into the study (Fig. 3),
`
`450
`
`ª 2006 L’Ore´al. Journal compilation
`ª 2006 Society of Cosmetic Scientists and the Socie´te´ Franc¸aise de Cosme´tologie, 28, 447–451
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 12 of 27 PageID #: 357
`
`Evaluation of anti-wrinkle efficacy of adenosine-containing products
`
`M.L. Abella
`
`bellar frowns were also significantly improved by
`regular application of cream-containing adenosine.
`This double design has been useful to assess
`simultaneously wrinkles at
`two different
`sites.
`While FOITS has been extensively used on the
`crow’s feet area, experience is still limited on the
`glabella area, which is very relevant to the study
`of dynamic wrinkles.
`These data were obtained in a rigorously blinded
`manner and were obtained in comparison with a
`placebo cream. They are particularly striking given
`that while the study duration was 8 weeks positive
`results were observed as early as week 3.
`In conclusion, the data presented in this report
`strongly suggest that the long-term use of cosmetic
`products containing adenosine can significantly
`reduce existing ‘dynamic’ wrinkles, at least in the
`two facial areas studied (periorbital and glabellar
`regions), and thus can partially reverse the signs
`of chronological ageing.
`
`Acknowledgements
`
`I would like to thank Dr M. Rohr, who conducted
`the study, and Chantal Fanchon for her advice.
`
`References
`
`1. Braverman, I.M. and Fornferko, E. Studies on cutane-
`ous ageing: the elastin fibre network. J. Invest. Derma-
`tol. 78, 434–443 (1982).
`2. Amano, S., Matsunaga, Y., Akutsu, N., et al. Early
`ageing and Laminin 5, a key player in basement
`membrane care. XXII. FSCC International Congress,
`Berlin (2000).
`3. Weiss, J.S., Ellis, C.N., Headington, J.T. et al. Topical
`tretinoin improved photoaged skin: a double blinded,
`vehicle
`controlled study.
`JAMA 159, 527–532
`(1988).
`4. Rona, C., Vailati, F. and Berardesca, E. The cosmetic
`treatment of wrinkles. J. Cosmet. Dermatol. 3, 26–34
`(2004).
`in vivo
`5. Rohr, M. and Schrader, K. Fast Optical
`Topometry of Human Skin (FOITS). SOFW J. 124,
`52–54 (1998).
`6. Rohr, M., Brandt, M. and Schrader, K. Skin surface
`claim supported by FOITS. SOFW J. 126, 2–11
`(2000).
`
`Rz
`Ra
`
`3
`Week of study
`
`8
`
`0
`
`–5
`
`correction for placebo
`
`% Reduction in R value after
`
`–10
`
`0
`
`Figure 3 Effects of adenosine-containing cream on gla-
`bellar frowns after application of cream C. Data from
`FOITS analysis of skin smoothness parameters Rz and Ra
`are plotted against time as described in the legends to
`Figs 1 and 2.
`
`with a significantly different evolution vs. placebo
`for both parameters (P £ 0.05, Tukey test).
`
`Discussion
`
`The present study shows that application of cos-
`metic preparations containing adenosine signifi-
`cantly reduced facial wrinkles. Data from FOITS
`analysis
`indicate
`that
`periorbital
`lines were
`reduced by both a cream and a dissolvable film
`containing adenosine.
`The FDH analysis, by separating the effects on
`different classes of wrinkles according to their
`depth, gives further information. The beneficial
`effect of an anti-wrinkle product is characterized
`by an improvement of the micro-relief (correspond-
`ing to an increase of the class of 0–50 lm depth
`lines) together with an improvement of the coarse
`wrinkles (which corresponds to a decrease of the
`class 115–600 lm). While it is well accepted that
`a good moisturizer is able to improve micro-relief,
`only real anti-wrinkle products may significantly
`reduce coarse wrinkles. As shown in Fig. 2 with
`the
`adenosine-containing
`products,
`beneficial
`effects on micro-relief are observed for both C
`cream and A dissolvable film, together with an
`impressive beneficial effect on coarse wrinkles. Gla-
`
`ª 2006 L’Ore´al. Journal compilation
`ª 2006 Society of Cosmetic Scientists and the Socie´te´ Franc¸aise de Cosme´tologie, 28, 447–451
`
`451
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 13 of 27 PageID #: 358
`Case 1:17-cv-00868—JFB-SRF Document 17-1 Filed 08/23/17 Page 13 of 27 PageID #: 358
`
`EXHIBIT D
`
`EXHIBIT D
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 14 of 27 PageID #: 359
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`UNIVERSITY OF MASSACHUSETTS
`MEDICAL SCHOOL and CARMEL
`LABORATORIES, LLC,
`
`Plaintiffs,
`
`v.
`
`L’ORÉAL S.A. and L’ORÉAL USA, INC.,
`
`Defendants.
`
`Civil Action No. 17-cv-868-JFB-SRF
`
`JURY TRIAL DEMANDED
`
`FIRST AMENDED COMPLAINT FOR PATENT INFRINGEMENT
`
`1.
`
`Plaintiffs UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL
`
`(“UMass”) and CARMEL LABORATORIES, LLC (“Carmel Labs”) for their Complaint against
`
`Defendants L’ORÉAL S.A. (“L’Oréál”) and L’ORÉAL USA, INC. (“L’Oréál USA”) (together,
`
`“Defendants”) allege:
`
`THE PARTIES
`
`1.
`
`Plaintiff UMass is a public institution of higher education with its principal
`
`address at 333 South Street, Suite 400, Shrewsbury, MA 01545.
`
`2.
`
`Teresian Carmelites, Inc. (“Teresian Carmelites”) is a non-profit religious
`
`organization with its principal address at 167 Riverlin Street, Millbury, MA 01527.
`
`3.
`
`Plaintiff Carmel Labs is a limited liability company with its principal place of
`
`business at 167 Riverlin Street, Millbury, MA 01527. Carmel Labs is a wholly-owned for-profit
`
`subsidiary of Teresian Carmelites. Profits realized by Carmel Labs are used to support Teresian
`
`Carmelites’ charitable works.
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 15 of 27 PageID #: 360
`
`4.
`
`UMass is the assignee and Carmel Labs is the exclusive licensee of United States
`
`Patent Numbers 6,423,327 (attached as Exhibit 1) and 6,645,513 (attached as Exhibit 2) (the
`
`“patents-in-suit”).
`
`5.
`
`Plaintiffs are informed and believe, and on that basis allege, that Defendant
`
`L’Oréal is a French corporation with its principal place of business at 41 Rue Martre, Clichy,
`
`Paris, Ile-de-France 92117, France.
`
`6.
`
`Plaintiffs are informed and believe, and on that basis allege, that Defendant
`
`L’Oréal USA is a Delaware corporation with its principal place of business at 10 Hudson Yards,
`
`New York, NY 10001. Plaintiffs are further informed and believe that L’Oréal USA’s registered
`
`agent is The Prentice-Hall Corporation System, Inc., 2711 Centerville Road Suite 400,
`
`Wilmington, DE 19808.
`
`7.
`
`L’Oréal USA is a wholly-owned subsidiary of L’Oréal. On information and belief,
`
`L’Oréal USA is the agent of L’Oréal, which controls or otherwise directs and authorizes the
`
`activities of L’Oréal USA.
`
`JURISDICTION AND VENUE
`
`8.
`
`The court has subject matter jurisdiction pursuant to 28 U.S.C. §§ 1331 and
`
`1338(a) because this action arises under the patent laws of the United States, 35 U.S.C. §§ 1 et
`
`seq. Venue is proper in this federal district pursuant to 28 U.S.C. §§ 1391(b)-(c) and 1400(b).
`
`THE CLAIMED ADENOSINE TECHNOLOGY
`
`9.
`
`Adenosine is a naturally occurring purine nucleoside that plays an important role
`
`in a variety of biochemical processes. It is used by physicians in therapeutic and diagnostic
`
`cardiac applications, for example, to treat arrthymias or during cardiac stress tests.
`
`10.
`
`Dr. James G. Dobson, Jr., a renowned cardiovascular physiologist and the former
`
`Chairman of the Department of Physiology at the University of Massachusetts Medical School,
` 2
`
`

`

`Case 1:17-cv-00868-JFB-SRF Document 17-1 Filed 08/23/17 Page 16 of 27 PageID #: 361
`
`has been conducting research on adenosine since approximately the mid 1960’s. Dr. Dobson
`
`and his colleague, Dr. Michael Ethier, discovered that topical application of adenosine can be
`
`used to enhance the condition of the skin by applying adenosine to the dermal cells in specified
`
`concentrations without increasing dermal cell proliferation.
`
`11.
`
`Their discoveries are embodied in U.S. Patent Nos. 6,423,327 (the “’327 patent”)
`
`and 6,645,513 (the “’513 patent”) (collectively, the “patents-in-suit”).
`
`12.
`
`Claim 1 of the ’327 patent recites, for example: “A method for enhancing the
`
`condition of unbroken skin of a mammal by reducing one or more of wrinkling, roughness,
`
`dryness, or laxity of the skin, without increasing dermal cell proliferation, the method comprising
`
`topically applying to the skin a composition comprising a concentration of adenosine in an
`
`amount effective to enhance the condition of the skin without increasing dermal cell
`
`proliferation, wherein the adenosine concentration applied to the dermal cells is 10−4 M to 10−7
`
`M.” Claim 1 of the ’513 patent r