`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`A,
`(OX
`Address: COMMISSIONER FOR PATENTS
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`FILING or
`371(c) DATE
`10/29/2007
`
`GRP ART
`UNIT
`
`
`
`
`
`FIL
`
`FEE REC'D
`210
`
`ATTY.DOCKET.NO
`NATNUT-30224/US/PRO
`CONFIRMATIONNO. 5450
`
`ITOT CLAIMSIND CLAIMS
`
`FILING RECEIPT
`
`
`
`APPLICATION
`NUMBER
`60/983,446
`
`72960
`Casimir Jones, S.C.
`
`440Science Drive A
`
`Madison, WI 53711
`
`Date Mailed: 11/09/2007
`
`It will not be examined for patentability and will
`Receipt is acknowledged of this provisional patent application.
`become abandonednotlater than twelve monthsafter its filing date. Any correspondence concerning the application
`mustinclude the following identification information: the U.S. APPLICATION NUMBER, FILING DATE, NAME OF
`APPLICANT, and TITLE OF INVENTION. Feestransmitted by checkor draft are subject to collection. Please verify
`the accuracy of the data presented on this receipt. If an error is noted on this Filing Receipt, please write to the
`Office of Initial Patent Examination's Filing Receipt Corrections. Please provide a copyof this Filing Receipt
`with the changes noted thereon. If you received a "Notice to File Missing Parts"for this application, please
`submit any corrections to this Filing Receipt with your reply to the Notice. When the USPTO processes the
`reply to the Notice, the USPTO will generate another Filing Receipt incorporating the requested corrections
`
`Applicant(s)
`
`Inge Bruheim, Volda, NORWAY;
`Mikko Griinari, Espoo, FINLAND;
`Jeffrey Cohn, Sydney, AUSTRALIA;
`Powerof Attorney: The patent practitioners associated with Customer Number 72960
`
`If Required, Foreign Filing License Granted: 11/01/2007
`
`The country code and number of your priority application, to be usedfor filing abroad under the Paris Convention,
`is US 60/983,446
`Projected Publication Date: None, application is not eligible for pre-grant publication
`
`Non-Publication Request: No
`
`Early Publication Request: No
`Title
`
`Method Of Improving Adipose Tissue Functioning And Lipid Metabolism
`
`PROTECTING YOUR INVENTION OUTSIDE THE UNITED STATES
`
`Since the rights granted by a U.S. patent extend only throughoutthe territory of the United States and have no
`effect in a foreign country, an inventor who wishes patent protection in another country must apply for a patent
`in a specific country or in regional patent offices. Applicants may wish to consider the filing of an international
`application under the Patent Cooperation Treaty (PCT). An international (PCT) application generally has the same
`effect as a regular national patent application in each PCT-member country. The PCT process simplifies the filing
`of patent applications on the same invention in member countries, but does notresult in a grantof "an international
`page 1 of 3
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0001
`
`page 0001
`
`
`
`patent" and doesnoteliminate the needof applicantsto file additional documents and fees in countries where patent
`protection is desired.
`
`Almost every country has its own patent law, and a person desiring a patent in a particular country must make an
`application for patent in that country in accordancewith its particular laws. Since the laws of many countries differ
`in various respects from the patent law of the United States, applicants are advised to seek guidance from specific
`foreign countries to ensure that patent rights are not lost prematurely.
`
`Applicants also are advised that in the case of inventions madein the United States, the Director of the USPTO must
`issue a license before applicants can apply for a patent in a foreign country. Thefiling of a U.S. patent application
`serves as a request for a foreign filing license. The application's filing receipt contains further information and
`guidance asto the status of applicant's license for foreign filing.
`
`Applicants may wish to consult the USPTO booklet, "General Information Concerning Patents”(specifically, the
`section entitled "Treaties and Foreign Patents") for more information on timeframes and deadlinesfor filing foreign
`patent applications. The guide is available either by contacting the USPTO Contact Center at 800-786-9199, or it
`can be viewed on the USPTO website at http://“www.uspto.gov/web/offices/pac/doc/general/index.html.
`
`For information on preventing theft of your intellectual property (patents, trademarks and copyrights), you may wish
`to consult the U.S. Government website, http:/Avww.stopfakes.gov. Part of a Department of Commerceinitiative,
`this website includes self-help "toolkits" giving innovators guidance on how to protectintellectual property in specific
`countries such as China, Korea and Mexico. For questions regarding patent enforcementissues, applicants may
`call the U.S. Governmenthotline at 1-866-999-HALT (1-866-999-4158).
`
`LICENSE FOR FOREIGN FILING UNDER
`
`Title 35, United States Code, Section 184
`
`Title 37, Code of Federal Regulations, 5.11 & 5.15
`
`GRANTED
`
`if the phrase "IF REQUIRED, FOREIGN FILING
`The applicant has been granted a license under 35 U.S.C. 184,
`LICENSE GRANTED"followed by a date appears on this form. Such licenses are issuedin all applications where
`the conditions for issuance of a license have been met, regardless of whether or not a license may be required as
`set forth in 37 CFR 5.15. The scope andlimitations of this license are set forth in 37 CFR 5.15(a) unless an earlier
`license has been issued under 37 CFR 5.15(b). The license is subject to revocation upon written notification. The
`date indicatedis the effective date of the license, unless an earlier license of similar scope has been granted under
`37 CFR 5.13 or 5.14.
`
`This licenseis to be retained by the licensee and maybe usedat any time onor after the effective date thereof unless
`it is revoked. This license is automatically transferred to any related applications(s) filed under 37 CFR 1.53(d). This
`license is not retroactive.
`
`The grantof a license doesnot in any way lessen the responsibility of a licensee for the security of the subject matter
`as imposed by any Governmentcontract or the provisions of existing laws relating to espionage and the national
`security or the export of technical data. Licensees should apprise themselvesof current regulations especially with
`respect to certain countries, of other agencies, particularly the Office of Defense Trade Controls, Department of
`State (with respect to Arms, Munitions and Implements of War (22 CFR 121-128)); the Bureau of Industry and
`page 2 of 3
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0002
`
`page 0002
`
`
`
`Security, Department of Commerce (15 CFR parts 730-774); the Office of Foreign AssetsControl, Department of
`Treasury (31 CFR Parts 500+) and the Department of Energy.
`
`NOT GRANTED
`
`No license under 35 U.S.C. 184 has been granted at this time, if the phrase "IF REQUIRED, FOREIGN FILING
`LICENSE GRANTED" DOESNOTappear on this form. Applicant maystill petition for a license under 37 CFR 5.12,
`if a license is desired before the expiration of 6 months from thefiling date of the application. If 6 months has lapsed
`from thefiling date of this application and the licensee has not received any indication of a secrecy order under 35
`U.S.C. 181, the licensee mayforeign file the application pursuant to 37 CFR 5.15(b).
`
`page 3 of 3
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0003
`
`page 0003
`
`
`
`PTO/SB/14 (06-07)
`Approved for use through 06/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`document maybe printed and included in a paper filed application.
`
`Application Data Sheet 37 CFR 1.76
`
`—
`
`Title of Invention
`
`Method of improving adipose tissue functioning and lipid metabolism
`
`The application data sheetis part of the provisional or nonprovisional application for whichit is being submitted. The following form contains the
`bibliographic data arranged in a format specified by the United States Patent and Trademark Office as outlined in 37 CFR 1.76.
`This document may be completed electronically and submitted to the Office in electronic format using the Electronic Filing System (EFS) or the
`
`Secrecy Order 37 CFR 5.2
`[_] Portions or all of the application associated with this Application Data Sheet mayfall under a Secrecy Order pursuant to
`
`3/7 CFR 5.2 (Paper filers only. Applications that fall under Secrecy Order may not befiled electronically.)
`
`Applicant Information:
`
`Applicant 1
`Applicant Authority ®!nventor|ClLegal Representative under 35 U.S.C. 117 C©Party ofInterest under 35 U.S.C. 118
`
`Prefix} Given Name
`Middle Name
`Family Name
`Suffix
`
`Residence Information (Select One) @) US Residency
`(© NonUS Residency
`(©) Active US Military Service
`City|Volda|State/Province|_| Country of Residencd|NO
`Citizenship under 37 CFR 1.41 (bj
`NO
`Mailing Address of Applicant:
`
`Martavegen 6 A
`
`Address1
`
`Address 2
`
`City
`
`Volda
`
`Postal Code
`
`State/Province
`
`NO
`
`
`
`Applicant 2
`Applicant Authority @) Inventor|(© Legal Representative under 35 U.S.C. 117 ©pPartyofInterest under 35 U.S.C. 118
`
`Prefix)GivenName Middle Name
`Family Name
`Suffix
`a
`Residence Information (Select One) @ US Residency
`(© NonUS Residency ©) Active US Military Service
`City|Espoo|State/Province|_| Country of Residencd|FI
`Citizenship under 37 CFR 1.41(b}
`Mailing Address of Applicant:
`Address1
`Kultarinnantie 1 b
`
`Address 2
`
`City
`
`Espoo
`
`Postal Code
`
`State/Province
`
`Fl
`
`Applicant 3
`Applicant Authority ®!nventor|ClLegal Representative under 35 U.S.C. 117 ©Party ofInterest under 35 U.S.C. 118
`
`Prefix} Given Name
`Middle Name
`Family Name
`Suffix
`
`Residence Information (Select One)
`(@) US Residency
`(©) NonUS Residency
`() Active US Military Service
`
`city|sysney|StatelProvince|| Crannertiistiderstpr’ 1003 page 000
`RIMFROST EXHIBIT 1003 page 0004
`
`EFS Web 2.2.0
`
`
`
`PTO/SB/14 (06-07)
`Approved for use through 06/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`Application Data Sheet 37 CFR 1.76
`
`—
`Application Number
`
`Title of Invention
`
`Method of improving adipose tissue functioning and lipid metabolism
`
`generated within this form by selecting the Add button.
`
`Mailing Address of Applicant:
`Address1
`
`Address 2
`
`All
`
`Inventors Must Be Listed - Additional
`
`Inventor
`
`Information blocks may be r
`
`CorrespondenceInformation:
`
`Enter either Customer Number or complete the Correspondence Information section below.
`For further information see 37 CFR 1.33(a).
`
`[_] An Addressis being provided for the correspondenceInformation of this application.
`
`Customer Number
`
`72960
`
`
`
`Email Address jmjones@casimirjones.com i|
`
`Application Information:
`
`Title of the Invention
`
`Method of improving adipose tissue functioning and lipid metabolism
`
`[SuggestedTechnologyCenter@fam)[CS
`
`
`Total Number of Drawing Sheets(if any) Po Suggested Figure for Publication (if any)||
`Publication Information:
`
`[_] Request Early Publication (Fee required at time of Request 37 CFR 1.219)
`
`
`
`eighteen months after filing.
`
`
`Request Not to Publish. | hereby requestthat the attached application not be published under 35 U.S.
`C. 122(b) and certify that the invention disclosed in the attached application has not and will not be the subject of
`an application filed in another country, or under a multilateral international agreement, that requires publication at
`
`Representative Information:
`
`Representative information should be provided for all practitioners having a power of attorney in the application. Providing
`this information in the Application Data Sheet does not constitute a power of attorney in the application (see 37 CFR 1.32).
`
`
`
`
`
`Enter the Representative Name_sectioneither Customer Number or complete below. If both sections
`
`
`are completed the Customer Number will be used for the Representative Information during processing.
`
`
`
`
`
`Please Select One:|@CustomerNumber|OUSPatentPragiienreROOT HRPBETTHR
`RIMFROST EXHIBIT 1003 page 0005
`
`EFS Web 2.2.0
`
`
`
`PTO/SB/14 (06-07)
`Approved for use through 06/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`Application Data Sheet 37 CFR 1.76
`
`Method of improving adipose tissue functioning and lipid metabolism
`
`Customer Number
`
`72960
`
`Domestic Benefit Information:
`
`This section allows for the applicant to claim benefit under 35 U.S.C. 119(e), 120, 121, or 365(c). Providing this information in the
`application data sheet constitutes the specific reference required by 35 U.S.C. 119(e) or 120, and 37 CFR 1.78(a)(2) or CFR 1.78(a)
`(4), and need not otherwise be made part of the specification.
`
`Application
`
`.
`
`Prior Application
`
`Filing Date
`
`Issue Date
`
`Additional Domestic Priority Data may be generated within this form by selecting
`
`Foreign Priority Information:
`This section allows for the applicant to claim benefit of foreign priority and to identify any prior foreign application for which priority is
`not claimed. Providing this information in the application data sheet constitutes the claim for priority as required by 35 U.S.C. 119(b)
`and 37 CFR 1.55(a).
`
`— Title of Invention
`the Add button.
`Add button.
`button.
`
`Application Number
`ParentFiling Date (YYYY-MM-DD)
`Priority Claimed
`——CSC~*iYes
`Additional Foreign Priority Data may be generated within this form by selecting the
`
`AssigneeInformation:
`Providing this information in the application data sheet does not substitute for compliance with any requirement of part 3 of Title 37
`of the CFR to have an assignment recorded in the Office.
`
`Assignee 1
`If the Assignee is an Organization check here.
`
`Xx
`
`Organization Name|Aker BioMarine ASA
`
`Mailing Address Information:
`
`Address1
`
`Address 2
`
`Fjordalléen 16
`
`P. O. Box 1423 Vika
`
`Email Address
`
`merete.kildahl@akerbiomarine.com
`
`Additional Assignee Data may be generated within this form by selecting the Add
`
`Signature:
`A signature of the applicant or representative is required in accordancewitpOoy" EXHIBIT OdFS°$280006
`RIMFROST EXHIBIT 1003 page 0006
`CFR 1.4(d) for the form of the signature.
`EFS Web 2.2.0
`
`
`
`PTO/SB/14 (06-07)
`Approved for use through 06/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`Application Data Sheet 37 CFR 1.76
`
`—
`
`2007-10-29
`
`Sansone[aMitchellJones/
`
`Title of Invention
`
`Method of improving adipose tissue functioning and lipid metabolism
`
`Date (YYYY-MM-DD)|
`
`This collection of information is required by 37 CFR 1.76. The information is required to obtain or retain a benefit by the public which
`is to file (and by the USPTO to process) an application. Confidentiality is governed by 35 U.S.C. 122 and 37 CFR 1.14. This
`collection is estimated to take 23 minutes to complete, including gathering, preparing, and submitting the completed application data
`sheet form to the USPTO. Time will vary depending upon the individual case. Any comments on the amount of time you require to
`complete this form and/or suggestions for reducing this burden, should be sent to the Chief Information Officer, U.S. Patent and
`Trademark Office, U.S. Department of Commerce, P.O. Box 1450, Alexandria, VA 22313-1450. DO NOT SEND FEES OR
`COMPLETED FORMS TO THIS ADDRESS. SEND TO: Commissioner for Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`EFS Web 2.2.0
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0007
`
`page 0007
`
`
`
`Privacy Act Statement
`
`The information provided by you in this form will be subject to the following routine uses:
`
`1.
`
`The information on this form will be treated confidentially to the extent allowed under the Freedom of Information Act (5 U.S.C. 552)
`and the Privacy Act (5 U.S.C. 552a). Records from this system of records may be disclosed to the Department of Justice to determine
`whether the Freedom of Information Act requires disclosure of these records.
`
`A record from this system of records maybe disclosed, as a routine use, in the course of presenting evidence to a court, magistrate, or
`administrative tribunal, including disclosures to opposing counselin the course of settlement negotiations.
`
`A record in this system of records maybedisclosed, as a routine use, to a Member of Congress submitting a request involving an
`individual, to whom the record pertains, whenthe individual has requested assistance from the Member with respect to the subject matter of
`the record.
`
`A record in this system of records maybe disclosed, as a routine use, to a contractor of the Agency having need for the information in
`order to perform a contract. Recipients of information shall be required to comply with the requirements of the Privacy Act of 1974, as
`amended, pursuant to 5 U.S.C. 552a(m).
`
`A record related to an International Application filed under the Patent Cooperation Treaty in this system of records may be disclosed,
`as a routine use, to the International Bureau of the World Intellectual Property Organization, pursuant to the Patent Cooperation Treaty.
`
`A record in this system of records maybedisclosed, as a routine use, to another federal agency for purposes of National Security
`review (35 U.S.C. 181) and for review pursuant to the Atomic Energy Act (42 U.S.C. 218(c)).
`
`A record from this system of records may be disclosed, as a routine use, to the Administrator, General Services, or his/her designee,
`during an inspection of records conducted by GSAaspart of that agency's responsibility to recommend improvementsin records
`managementpractices and programs, under authority of 44 U.S.C. 2904 and 2906. Such disclosure shall be made in accordance with the
`GSAregulations governing inspection of records for this purpose, and any otherrelevant (i.e., GSA or Commerce) directive. Such
`disclosure shall not be used to make determinations aboutindividuals.
`
`A record from this system of records maybe disclosed, as a routine use, to the public after either publication of the application pursuant
`to 35 U.S.C. 122(b) or issuance of a patent pursuant to 35 U.S.C. 151. Further, a record may be disclosed, subject to the limitations of 37
`CFR 1.14, as a routine use, to the public if the record wasfiled in an application which became abandonedor in which the proceedings were
`terminated and which application is referenced by either a published application, an application open to public inspections or an issued
`patent.
`
`A record from this system of records maybe disclosed, as a routine use, to a Federal, State, or local law enforcement agency, if the
`USPTO becomesawareofa violation or potential violation of law or regulation.
`
`The Privacy Act of 1974 (P.L. 93-579) requires that you be given certain information in connection with your submission of the attached form related to
`a patent application or patent. Accordingly, pursuant to the requirements of the Act, please be advised that:
`(1) the general authority for the collection
`of this information is 35 U.S.C. 2(b)(2); (2) furnishing of the information solicited is voluntary; and (3) the principal purpose for which the information is
`used by the U.S. Patent and Trademark Office is to process and/or examine your submission related to a patent application or patent.
`If you do not
`furnish the requested information, the U.S. Patent and Trademark Office may not be able to process and/or examine your submission, which may
`result in termination of proceedings or abandonmentof the application or expiration of the patent.
`
`page 0008
`
`EFS Web 2.2.0
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0008
`
`
`
`Methodof improving adipose tissue functioning and lipid metabolism
`
`Inventors: Inge Bruheim (Volda, Norway), Mikko Griinari (Espoo, Finland) and Jeffrey Cohn
`
`(Sydney, Australia)
`
`FIELD OF THE INVENTION
`
`This invention relates to the specific uses ofkrill oil
`
`BACKGROUNDOF THE INVENTION
`
`10
`
`Krill oil has been disclosed targeting classical health problems such as cardiovascular risk
`
`factors, joint pain, cognitive problems,controlling diabetes and menstrual pain [1-5]. More
`
`specifically, krill oil compositions have been described as being effective for decreasing
`
`cholesterol,
`
`inhibiting platelet adhesion,
`
`inhibiting artery plaque formation, preventing
`
`hypertension, controlling athritis symptoms, preventing skin cancer, enhancing transdermal
`
`15
`
`transport, reducing the symptoms of premenstrual symptoms or controlling blood glucose
`
`levels in a patient [1]. Krill oil has not been disclosed as being effective in treating one of the
`
`most important life style problem of modernsocieties i.e. excess weight gain and obesity.
`
`Excess adipose tissue mass
`
`(overweight and obesity)
`
`is associated with low grade
`
`20
`
`inflammation in adipose tissue and in the whole body reflecting the inflammatory mediators
`
`“spilling over’ from fat tissue [6]. Inflammation appears to be an important link between
`
`obesity and metabolic syndrome/type-II diabetes as well as cardiovascular disease [7]. Thus,
`
`excess adipose tissuc is an unhcalthy condition. Weight
`
`reduction will
`
`improve the
`
`inflammatory condition, but persistent weight reduction is difficult to achieve. Omega-3 fatty
`
`25
`
`acid supplementation may alleviate the inflammatory condition in adipose tissue and thus
`
`ideally complement the principal strategies of weight reduction i.e.
`
`low calorie diet and
`
`exercise. There are clinical studies in humans that demonstrate that omega-3 enhance the
`
`effect of very low calorie diet [8] and exercise [9] in reducing body fat mass. Although diet
`
`and exercise regime may fail to result in consistent decrease in weight in long term, the effect
`
`30
`
`of omega-3 fatty acids alleviating the inflammatory condition in the adipose tissue maypersist
`
`generating a condition that can be described as "healthy adipose tissue". Previously, it was
`
`shown [10] that dictary omcga-3 fatty acids can be used to reduce inflammation in adipose
`
`tissue without influencing level of obesity. Reduction in adipose tissue inflammation was
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0009
`
`page 0009
`
`
`
`demonstrated by an increase in circulating levels of adiponectin. Adiponectin is an adipose
`
`tissue derived anti-inflammatory hormone. Results on the treatment of obese people with
`
`omcega-3 fatty acids to alleviate circulating levels of inflammatory markcrs are inconclusive
`
`[11]. However, duration of these studies may not have been sufficient given the slow turnover
`
`of adipose tissue in humans. Itoh et al. [12] found that 1.8 g/d of EPA increased adiponectin, a
`
`marker of adipose tissue derived inflammation,
`
`in a group of overweight subjects with
`
`metabolic syndrome.
`
`SUMMARYOF THE INVENTION
`
`10
`
`This invention relates to the specific uses of krill oil. In some embodiments, the
`
`present invention provides methods of reducing diet-induced hyperinsulinemia, insulin
`
`insensitivity, muscle mass hypertrophy, scrum adiponcctin reduction or hepatic stcatosis
`
`comprising in a subject exposed to a high fat diet: administering to said subject exposedto a
`
`high fat diet an effective amountof a krill oil composition under conditions such that a
`
`15
`
`condition selected from the group consisting of diet-induced hyperinsulinemia,insulin
`
`insensitivity, muscle mass hypertrophy, serum adiponectin reduction and hepatic steatosis is
`
`reduced. The present invention is not limited to any particular krill oil composition. In some
`
`embodiments, the krill oil composition is a Euphausia superba krill oil composition. The
`
`present invention is not limited to any particular formulation of krill oil. In some
`
`20
`
`embodiments, the krill oil composition is encapsulated. In some preferred embodiments, the
`
`effective amount ofa krill oil composition is from 0.2 grams to 10 gramsofsaid krill oil
`
`composition. In some embodiments, the krill oil composition comprises: from about 45% to
`
`55% w/w phospholipids; from about 35% to 45% w/w triglycerides; and from about 400 to
`
`about 1500 ppm astaxanthin. In some embodiments, the krill oil composition comprises a
`
`25
`
`blendof lipid fractions obtained from Euphausia superba. In some embodiments, the krill oil
`
`composition comprises from about 25% to 30% omega-3 fatty acids as a percentage oftotal
`
`fatty acids and wherein from about 80% to 90% of said omega-3 fatty acids are attached to
`
`said phospholipids. In some embodiments, the krill oil composition comprises from about
`
`30% to 60% w/w phospholipids; from about 30% to 50% triglycerides; from about 400 to
`
`30
`
`about 1500 ppm astaxanthin; and from about 20% to 35% omega-3 fatty acids as a percentage
`
`of total fatty acids in said composition, and wherein from about 70% to 95% of said omega-3
`
`fatty acids are attached to said phospholipids.
`
`In some embodiments, the present invention provides methods of reducing diet-
`
`induced hyperinsulinemia, insulin insensitivity, muscle mass hypertrophy, serum adiponectin
`
`2
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0010
`
`page 0010
`
`
`
`reduction or hepatic steatosis comprising in a subject consuming a high fat diet or a normalfat
`
`diet: administering to said subject consuming a high fat diet or a normal fat diet an effective
`
`amountofa krill oil composition under conditions such that a condition selected from the
`
`group consisting of diet-induced hyperinsulinemia, insulin insensitivity, muscle mass
`
`hypertrophy, serum adiponectin reduction and hepatic steatosis is reduced. The present
`
`invention is not limited to any particular krill oil composition. In some embodiments, the krill
`
`oil composition is a Euphausia superbakrill oil composition. The present invention is not
`
`limited to any particular formulation ofkrill oil. In some embodiments, the krill oil
`
`composition is encapsulated. In some preferred embodiments, the effective amount ofa krill
`
`10
`
`oil composition is from 0.2 grams to 10 gramsof said krill oil composition. In some
`
`embodiments, the krill oil composition comprises: from about 45% to 55% w/w
`
`phospholipids; from about 35% to 45% w/w triglycerides; and from about 400 to about 1500
`
`ppm astaxanthin. In some embodiments,thekrill oil composition comprises a blend oflipid
`
`fractions obtained from Euphausia superba. In some embodiments, the krill oil composition
`
`15
`
`comprises from about 25% to 30% omega-3 fatty acids as a percentage of total fatty acids and
`
`wherein from about 80% to 90% of said omega-3 fatty acids are attached to said
`
`phospholipids. In some embodiments, the krill oil composition comprises from about 30% to
`
`60% w/w phospholipids; from about 30% to 50% triglycerides; from about 400 to about 1500
`
`ppm astaxanthin; and from about 20% to 35% omega-3 fatty acids as a percentage oftotal
`
`20
`
`fatty acids in said composition, and wherein from about 70% to 95% of said omega-3 fatty
`
`acids are attached to said phospholipids.
`
`DEFINITIONS
`
`25
`
`As used herein, "phospholipid" refers to an organic compound having the following general
`
`structure:
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0011
`
`page 0011
`
`
`
`wherein R1 is a fatty acid residue, R2 is a fatty acid residue or -OH, and R3 is a —H or
`nitrogen
`containing
`compound
`choline
`(HOCH2»CH2N’(CH;);0H),
`ethanolamine
`
`(HOCH2CH2NHz2), inositol or serine. R1 and R2 cannot simultaneously be OH. When R3 is
`
`an —OH, the compound is a diacylglycerophosphate, while when R3is a nitrogen-containing
`
`compound, the compoundis a phosphatide such as lecithin, cephalin, phosphatidyl serine or
`
`plasmalogen.
`
`10
`
`Asused herein, the term omega-3 fatty acid refers to polyunsaturated fatty acids that have the
`
`final double bond in the hydrocarbon chain between the third and fourth carbon atoms from
`
`the methyl end of the molecule. Non-limiting examples of omega-3 fatty acids include,
`
`5,8,11,14,17-eicosapentaenoic acid (EPA), 4,7,10,13,16,19-docosahexanoic acid (DHA) and
`
`7,10,13,16,19-docosapentanoic acid (DPA).
`
`15
`
`Asused herein, astaxanthin refers to the following chemicalstructure:
`
`
`
`Asused herein, astaxanthin esters refer to the fatty acids esterified to OH group in the
`
`astaxanthin molecule.
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0012
`
`page 0012
`
`
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`An embodiment of the invetion is the use of krill oil to increase serum adiponectin levels.
`
`Adiponectin is a protein hormone that modulates a number of metabolic processes, including
`
`glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose
`
`tissue into the bloodstream and is very abundantin plasmarelative to many hormones. Levels
`
`of the hormone are inversely correlated with body mass index (BMI). The hormoneplays a
`
`role in alleviating the metabolic dysregulation that may result in type 2 diabetes, obesity,
`
`10
`
`atherosclerosis and non-alcoholic fatty liver disease (NAFLD)[13-14].
`
`Another embodiment of the invention is to use krill oil in an overweight and obese subjects
`
`for alleviating diet induced adipose tissue dysfunction and diet induced changes in the lipid
`
`metabolism.
`
`This invention discloses that krill oil is effective in reducing risk factors of type 2 diabetes
`
`such as hyperinsulinemia and insulin resistance and cardiovascular disease risk factors in
`
`overweight subjetcs. In addition this invention discloses that krill oil is effective in preventing
`
`accumulation of fat in muscles andin the liver(liver steatosis).
`
`15
`
`20
`
`In some cmbodiments, the methods of the present invention utilize a krill oil composition,
`
`preferably a Euphausia superba krill oil composition, comprising from about 40% to about
`
`60% w/w phospholipids, preferably from about 45% to 55% w/w phospholipids and from
`
`about 300 ppm astaxanthin to about 2000 ppm astaxanthin, preferably from about 400 to
`
`25
`
`about 1500 ppm astaxanthin.
`
`In further embodiments, the compositions comprise from about
`
`35% to 45% w/w triglycerides; and from about 400 to about 1500 ppm astaxanthin.
`
`In some
`
`embodiments, the compositions comprise from about 20% to 35%, preferably from about 25%
`
`to 35%, omega-3 fatty acids as a percentage of total fatty acids in the composition, wherein
`
`from about 70% to 95%, preferably from about 80% to 90% of the omega-3 fatty acids are
`
`30
`
`attached to the phospholipids.
`
`In some embodiments,
`
`the compositions of this invention are contained in acceptable
`
`excipients and/or carriers for oral consumption. The actual form of the carrier, and thus, the
`
`composition itself, is not critical. The carrier may be a liquid, gel, gelcap, capsule, powder,
`
`5
`
`RIMFROST EXHIBIT 1003
`
`RIMFROST EXHIBIT 1003 page 0013
`
`page 0013
`
`
`
`solid tablet (coated or non-coated), or the like. The composition is preferably in the form of a
`
`tablet or capsule and most preferably in the form of a soft gel capsule. Suitable excipient
`
`and/or carricrs include maltodextrin, calcium carbonate, dicalcium phosphate,
`
`tricalctum
`
`phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid,
`
`croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums,
`
`lactose, methylcellulose, povidone, carboxymethylcellulose,
`
`corn starch, and the like
`
`(including mixtures thereof). Preferred carriers include calcium carbonate, magnesium
`
`stearate, maltodextrin, and mixtures thereof. The various ingredients and the excipient and/or
`
`carrier are mixed and formedinto the desired form using conventional techniques. The tablet
`
`10
`
`or capsule of the present invention may be coated with an enteric coating that dissolves at a
`
`pH of about 6.0 to 7.0. A suitable enteric coating that dissolves in the small intestine but not
`
`in the stomachis cellulose acetate phthalate. Further details on techniques for formulation for
`
`and administration may be foundin the latest edition of Remington's Pharmaceutical Sciences
`
`(Maack Publishing Co., Easton, PA).
`
`15
`
`The dietary supplement may comprise one or more inert ingredients, especially if it is
`
`desirable to limit the number of calories added to the diet by the dietary supplement. For
`
`example,
`
`the dietary supplement of the present
`
`invention may also contain optional
`
`ingredients
`
`including,
`
`for example, herbs, vitamins, minerals,
`
`enhancers,
`
`colorants,
`
`20
`
`sweeteners, flavorants, inert ingredients, and the like. For