Application/Control Number: 10/311 ,814
`Art Unit 1614
`
`Page2
`
`CLAIMS 1, 2, 11-13, 22-26, 30-33, 35, 37, 39, 41, 43, 45, 47 AND 49 ARE PRESENTED
`
`FOR EXAMINATION
`
`Applicants' Amendment and Information Disclosure Statement filed December 8, 2004
`
`have been received and entered into the application.
`
`Accordingly, claims 1, 2, 11-13, 22-26, 30-33, 35, 37, 39, 41 , 43, 45, 47 and 49 have
`
`been amended and claims 8-10, 18, 55-58 and 60-62 have been canceled. Also, as reflected by
`
`the attached, completed copy of form PT0-1449 ( 15 pages), the Examiner has considered the
`
`cited references.
`
`In view of the above amendments, and the remarks by Applicants at pages 7-8 of their
`
`amendment, the objections and rejections set forth in the previous Office action dated September
`
`8, 2004 are withdrawn.
`
`Upon further review of the claims as well as a consideration of the state of the art as
`
`represented by the references newly cited by Applicants, the following new objection and claim
`
`rejection under 35 U.S.C. § 112, first paragraph are deemed proper.
`
`Allowable Claims
`
`Claims 12 and 13 are io condition for allowance.
`
`Claim Objection
`
`Claim 1 is objected to as containing a grammatical error. The expression
`
`"stabilize/reduce/iron accumulation" at lines 4-5 should read as ---stabilize/reduce iron
`
`accumulation---. Appropriate correction is required.
`
`
`331 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit: 1614
`
`Page 3
`
`Claim Rejection-35USC§112, First Paragraph
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112:
`
`The specification shall contain a written description of the invention, and of the manner and process of making
`and using it, in such full, clear, concise, and e.itact terms as to enable any person skilled in the art to which it
`pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode
`contemplated by the inventor of carrying out his invention.
`
`Claims 1, 2, 11, 23-26, 30-33, 35, 37, 39, 41, 43, 45, 47 and 49 are rejected under 35
`
`U.S.C. 112, first paragraph, because the specification, while being enabling for treating,
`
`stabilizing or reducing/stabilizing the risk of iron-induced cardiac disease through the
`
`administration of deferiprone or a physiologically acceptable salt thereof, does not reasonably
`
`provide enablement for the prevention or reversal of such disease. The specification does not
`
`enable any person skilled in the art to which it pertains, or with which it is most nearly
`
`connected, to practice the invention commensurate in scope with these claims.
`
`Burden on the Examiner for Making a Rejection Under 3 5 U.S. C § 112 First
`
`As set forth in In re Marzocchi, 169 USPQ 367, 370 (CCPA 1971):
`
`Paragraph
`
`"[A] [s]pecification disclosure which contains teaching of manner and process of making
`and using the invention in terms corresponding to the scope to those used in describing and
`defining subject matter sought to be patented must be taken as in compliance with enabling
`requirement of first paragraph of35 U.S.C. 112 unless there is reason to doubt the objective
`truth of statements contain therein which must be relied on for enabling support; assuming that
`sufficient reason for such doubt exists, a rejection for failure to teach how to make and/or use
`will be proper on that basis, such a rejection can be overcome by suitable proofs indicating that
`teaching contained in specification is truly enabling." (emphasis added).
`
`Here, the objective truth of the statement that iron-induced cardiac disease could be
`
`prevented or reversed is doubted because the "prevention" or "reversal" of iron-induced cardiac
`
`disease is tantamount to a cure for such disease, while the art (see the references relied upon
`
`
`332 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit: 1614
`
`Page4
`
`infra) and Applicants teach that, at best, iron-induced cardiac disease may be effectively treated
`
`through the administration of the claimed active agent. Also, the state of the art concerning the
`
`treatment of iron-induced cardiac disease with chelation therapy appeared to be that some degree
`
`of cardiac disease would occur. Support for this conclusion is Applicants' statement at page 34
`
`of the present specification, lines 26-29 "Although effe.ctive iron chelation with desferrioxamine
`
`has been available for over 25 years, cardiac disease remains a frequent cause of morbidity and is
`
`still responsible for 70% of the deaths among patients with transfusion-dependent thalassemia
`
`patients (sic)."
`
`It is noted that prevention and reversal do not necessarily equate to the term "cure".
`
`However, such is a proper interpretation because it is broad and reasonable as provided for in the
`
`MPEP at section 2111 . ("Claims must be given their broadest reasonable interpretation
`
`consistent with the supporting description").
`
`A prevention, reversal of or cure for iron-induced cardiac disease each circumscribe
`
`methods of absolute success. Absolute success is not reasonably possible with most
`
`diseases/disorders and more than a mere allegation that deferiprone is effective for preventing or
`
`reversing iron-induced cardiac disease would be necessary to satisfy the enabling requirement in
`
`the face of the doubt expressed by the Examiner which is based on the state of the art at the time
`
`of the invention.
`
`Concerning the state of the art of treating iron-induced heart cardiac disease, Applicants
`
`have set forth in their response filed August 23, 2004 at page 19, last full sentence that "The data
`
`reveals that iron induced heart disease occurs even in patients who are compliant with
`
`desferroxamine and even for those who do not have high levels of total body iron assessed by
`
`
`333 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit: 1614
`
`Page 5
`
`serum ferretin or liver iron concentrations."(emphasis original). This statement satisfies the
`
`Examiner's burden of doubt as expressed in In re Marzocchi, Id. as such establishes the
`
`difficulty known to the skilled artisan in the mere treatment of the disease. Logic would dictate
`
`that if such difficulty is encountered while trying to manage the disease while it exists in a
`
`patient, the prevention or reversal of such a disease, where absolute success would need to be
`
`demonstrated, would be therapeutic goals not readily or reasonably expected by the skilled
`
`artisan. In order to imbue the artisan with at least a reasonable expectation that the prevention or
`
`reversal of iron-induced cardiac disease could be obtained through the mere administration of
`
`deferiprone or a physiologically acceptable salt thereof, the artisan would need to review clinical
`
`data where such prevention or reversal was shown. Because such data is lacking in the present
`
`specification, and the Examiner cannot locate data showing such prevention or reversal, it is the
`
`Examiner' s position that the artisan would not be enabled to practice the present invention in a
`
`manner commensurate in scope with the claims, which include both the prevention and reversal
`
`of iron-induced cardiac disease. The reference cited by Applicants, Liu, P. "Personal letter from
`
`Dr. Liu on reversal of the heart failure in a patient with thalassemia treated with deferiprone"
`
`(cited on page 8 of form PT0-1449) is noted in this regard, but is insufficiently detailed to
`
`diminish the propriety of the Examiner's position. That is, a determination of whether a cardiac
`
`disease was, in fact, reversed, would involve consideration of more than just an anecdotal report
`
`of nonnal ventricular function.
`
`It is noted that claims 1-2 are not directed to the prevention or reversal of iron-induced
`
`cardiac disease. The claims do, however, include the requirement that "further iron
`
`accumulation in the heart" is prevented. It is doubted that such accumulation could actually be
`
`
`334 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit: 1614
`
`Page 6
`
`prevented, i.e., no iron whatsoever accumulating in the heart following the initiation of
`
`deferiprone therapy, because therapy with a related drug, i.e., desferroxxamine, was not known
`
`to be totally effective in removing iron-induced cardiac disease in patients who are compliant
`
`with therapy (see Applicants' remarks relied on above, i.e., "The data reveals ... ") and because
`
`the cardiac disease is characterized as "iron induced", it may be reasonably presumed that some
`
`level of iron would continue to accumulate so as to further contribute to the disease.
`
`Further supporting the Examiner' s doubt as to the accuracy of Applicants' statements
`
`that iron-induced cardiac disease may be prevented or reversed through the administration of
`
`deferiprone or a physiologically acceptable salt thereof are the following statements which
`
`appear to indicate the efficacy of deferiprone in only reducing the risk of such disease, rather
`
`than actually preventing or reversing the disease:
`
`"Applicant's (sic) have discovered that the administration of effective amounts of
`
`deferiprone results in patients being at less risk of developing cardiac disease than a patient
`
`treated with desferroxamine."(emphasis added) (Applicants' amendment filed August 23, 2004
`
`at page 20, middle of the second paragraph); and
`
`"This specification teaches an even greater protective effect than could be expected from
`
`overall body iron reduction alone." (emphasis added) (Applicants' amendment filed August 23,
`
`2004 at page 20, third full paragraph).
`
`Also, the data in the present specification at pages 22-39 has also been noted, but does
`
`not demonstrate that the administration of deferiprone resulted in the prevention or reversal of
`
`iron-induced cardiac disease. The statement that "the successful reversal of the iron-induced
`
`congestive heart failure in a patient participating in the study provides evidence for the
`
`
`335 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311 ,814
`Art Unit: 1614
`
`Page7
`
`cardioprotective effect of this iron chelator'' references the above mentioned Liu, P. "Personal
`
`letter from Dr. Liu on reversal of the heart failure in a patient with thalassernia treated with
`
`deferiprone" reference (cited on page 8 of form PT0-1449). This anecdotal report fails to
`
`establish, however, that the heart disease, was in fact, "reversed" . The reference does not
`
`provide objective data upon which the author's opinion is based and it is further not believed that
`
`the results demonstrated in but a single patient provides meaningful information upon which to
`
`base a reasonable conclusion respecting the efficacy of deferiprone on iron-induced cardiac
`
`disease.
`
`Summary
`
`As the cited art and discussion above establish, practicing the claimed method in the
`
`manner disclosed by Applicants would not imbue the skilled artisan with a reasonable
`
`expectation that the iron-induced cardiac disease could be prevented or reversed or that iron
`
`accumulation in the heart could be prevented, i.e., no accumulation of iron whatsoever. In order
`
`to actually achieve these objectives, it is clear from the discussion above that the skilled artisan
`
`could not rely on Applicant's disclosure as required by 35 U.S.C. § 112, first paragraph. Given
`
`that the art fails to recognize, and Applicants have failed to demonstrate, that iron-induced
`
`cardiac disease could actually be prevented or reversed, the skilled artisan would be faced with
`
`the impermissible burden of undue experimentation in order to practice this embodiment of the
`
`claimed invention.
`
`Accordingly, the claims are deemed properly rejected.
`
`Claim Rejection - 35USC§112, Second Paragraph
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`
`336 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit: 1614
`
`Page8
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the
`subject matter which the applicant regards as his invention.
`
`Claims 22-24, 30-33, 35, 37, 39, 41, 43, 45, 47 and 49 are rejected under 35 U.S.C. 112,
`
`second paragraph, as being indefinite for failing to particularly point out and distinctly claim the
`
`subject matter which applicant regards as the invention.
`
`"The primary purpose of this requirement of definiteness of claim language is to ensure
`
`that the scope of the claims is clear so the public is informed of the boundaries of what
`
`constitutes infringement of the patent. A secondary purpose is to provide a clear measure of what
`
`applicants regard as the invention so that it can be detennined whether the claimed invention
`
`meets all the criteria for patentability and whether the specification meets the criteria of 35
`
`U.S .C. 112, first paragraph with respect to the claimed invention." (MPEP 2173).
`
`The phrase "less critical" in the expression "less critical organs/tissue in the body"
`
`(claims 22-24) and "substantially" in the expression "substantially in the range of.." (claims 35,
`
`37 and 39) are relative terms which renders the claim indefinite. The phrase "less critical" and
`
`"substantially" are not defined by the claim, the specification does not provide a standard for
`
`ascertaining the requisite degree, and thus one of ordinary skill in the art would not be
`
`reasonably apprised of the scope of the invention.
`
`The terms "less critical" and "substantially" would invite subjective interpretations of
`
`whether or not a particular dosage amount of deferiprone or a physiologically acceptable salt
`
`thereof is included by or excluded from the present claims and it is thus the Examiner's position
`
`that the public would not be informed of the boundaries of what constitutes infringement of the
`
`present claims. Therefore, the claims fail to meet either the tenor or express requirements of 35
`
`U.S.C. § 112, second paragraph and are properly rejected.
`
`
`337 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Application/Control Number: 10/311,814
`Art Unit 1614
`
`Page9
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Raymond J. Henley Ill whose telephone number is 571-272-
`
`0575. The examiner can normally be reached on M-F, 8:30 am to 4:00 pm Eastern Time.
`
`If attempts to reach the examiner by telephone are unsuccessfu~ the examiner's
`
`supervisor, Christopher Low can be reached on 571-272-0951. The fax phone number for the
`
`organization where this application or proceeding is assigned is 703-872-9306.
`
`Information regarding the status of an application may be obtained from the Patent
`
`Application Information Retrieval (PAIR) system Status information for published applications
`
`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
`
`applications is available through Private PAIR only. For more information about the PAIR
`
`system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
`
`system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
`
`-~~fm-
`
`Primary Examiner
`Art Unit 1614
`
`March 22, 2005
`
`
`338 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`..
`
`Interview Summary
`
`Application No.
`
`10/311 ,814
`
`Examiner
`
`Applicant(s)
`
`SPINO ET AL
`
`Art Unit
`
`Raymond J. Henley Ill
`
`1614
`
`All participants (applicant, applicant's representative, PTO personnel):
`
`(1) Raymond J. Henley Ill.
`(2) bk.J.~- ~IA~µ..e,.s
`
`Date of Interview: 01 December 2004.
`
`(3) __ .
`
`(4) _ _ .
`
`Type: a)l8] Telephonic b)O Video Conference
`c)O Personal [copy given to: 1)0 applicant 2)0 applicant's representative]
`
`Exhibit shown or demonstration conducted: d)O Yes
`.
`If Yes, brief description: _ _
`
`e)181 No.
`
`Claim(s) discussed: All. generally.
`
`Identification of prior art discussed: None.
`
`Agreement with respect to the daims f)l81 was reached . g)O was not reached. h)O NIA.
`
`Substance of Interview including description of the general nature of what was agreed to if an agreement was
`reached, or any other comments: If all objections/rejections are overcome. the aoplication should be in condition for
`allowance ..
`
`(A fuller description, if necessary, and a copy of the amendments which the examiner agreed would render the claims
`allowable, if available, must be attached. Also, where no copy of the amendments that would render the claims
`allowable is available, a summary thereof must be attached.)
`
`THE FORMAL WRITTEN REPLY TO THE LAST OFFICE ACTION MUST INCLUDE THE SUBSTANCE OF THE
`INTERVIEW. (See MPEP Section 713.04). If a reply to the last Office action has already been filed, APPLICANT IS
`GIVEN ONE MONTH FROM THIS INTERVIEW DATE, OR THE MAILING DATE OF THIS INTERVIEW SUMMARY
`FORM, WHICHEVER IS LATER, TO FILE A STATEMENT OF THE SUBSTANCE OF THE INTERVIEW. See
`Summary of Record of Interview requirements on reverse side or on attached sheet.
`
`Examiner Note: You must sign this form unless ii is an
`Attachment to a signed Office action.
`
`U.S . Paten! anl Tnufamarl< O!!lce
`PTOL-413 (Rev. 04--03)
`
`Interview Summary
`
`Paper No. 03222005
`
`
`339 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Summary of Record of Interview Requirements
`
`Manual of Patent Examining Procedure (MPEP), Section 713.04, Substance of Interview Must be Made of Record
`A complete written statement as to the substance or any raco-to-face, video conference, or telephone intervi- with regard to an application must be made of record in the
`application whether or not an agreement with the examiner was reached at the interview.
`
`Title 37 Code of Federal Regulations (CFR) § 1.133 Interviews
`Paragraph {b)
`In every instance where reconsideration is requested in view of an intervi- with an examiner, a complete written statement of the reasons presented at the interview as
`warranting favorable action must be f~ed by tho applicant An interview does not remove tho necessity for reply to Of!leo action as specified in§§ 1.111 , 1.135. (35 U.S.C. 132)
`
`37 CFR § 1.2 Business to be transacted in writing.
`All business with the Patent or Trademark Office should be transacted In writing. The personal attendance or applicants or their attorneys or agents at the Patent and
`Trademark Office is unnecessary. The action of the Patent and Trademark Office will be based exclusively on the written record in the Office. No attention will be paid to
`any alleged oral promise, stipulation, or understanding In relation to which there Is disagreement or doubt.
`
`The action Of the Patent and Trademark Office cannot be based exclusively on the written record in the Office if that record is itself
`incomplete through the failure to record the substance of interviews.
`It is the responsibility of the applicant or the attorney or agent to make the substance of an interview of record in the application file, unless
`the examiner indicates he or she will do so. It is the examiner's responsibility to see that such a record is made and to correct material inaccuracies
`which bear directly on the question of patentability.
`Examiners must complete an Interview Summary Form for each interview held where a matter of substance has been discussed during the
`interview by checking the appropriate boxes and filling in the blanks. Discussions regarding only procedural matters, directed solely to restriction
`requirements for which interview recordation is otherwise provided for in Section 812.01 of the Manual of Patent Examining Procedure, or pointing
`out typographical errors or unreadable script in Office actions or the like, are excluded from the interview recordation procedures below. Where the
`substance of an interview is completely recorded in an Examiners Amendment, no separate Interview Summary Record is required.
`The Interview Summary Form shall be given an appropriate Paper No., placed in the right hand portion of the file. and listed on the
`•contents• section of the file wrapper. In a personal interview, a duplicate of the Form Is given to the applicant (or attorney or agent) at the
`conclusion of the interview. In the case of a telephone or video-conference interview, the copy is mailed to the applicant's correspondence address
`either with or prior to the nex1 official communication. If additional correspondence from the examiner is not likely before an allowance or if other
`circumstances dictate, the Form should be mailed promptty after the interview rather than wtth the nex1 official communication.
`
`The Form provides for recordation of the following Information:
`Application Number (Series Code and Serial Number)
`-
`Name of applicant
`Name of examiner
`Date of interview
`Type of interview (telephonic, video-conference, or personal)
`Name of participant(s) (applicant, attorney or agent .• examiner, other PTO personnel, etc.)
`An indication whether or not an exhibit was shown or a demonstration conducted
`An identification of the specific prior art discussed
`An indication whether an agreement was reached and if so, a description of the general nature of the agreement (may be by
`attachment of a copy of amendments or claims agreed as being allowable). Note: Agreement as to allowability is tentative and does
`not restrict further action by the examiner to the contrary.
`The signature of the examiner who conducted the interview (if Form is not an attachment to a signed Office action)
`
`It is desirable that the examiner orally remind the applicant of his or her obligation to record the substance of the interview of each case. It
`should be noted, however, that the Interview Summary Form will not normally be considered a complete and proper recordation of the interview
`unless it includes, or is supplemented by the applicant or the examiner to Include, all of the applicable items required below concerning the
`substance of the interview.
`
`A complete and proper recordation of the substance of any interview should include at least the following applicable items:
`1) A brief description of the nature Of any exhibit shown or any demonstration conducted,
`2) an identification of the claims discussed,
`3) an identification of the specific prior art discussed,
`4) an identification of the principal proposed amendments of a substantive nature discussed, unless these are already described on the
`Interview Summary Form completed by the Examiner,
`5) a brief identification of the general thrust of the principal arguments presented to the examiner,
`(The identification of arguments need not be lengthy or elaborate. A verbatim or highly detailed description of the arguments is not
`required. The identification of the arguments is sufficient if the general nature or thrust of the principal arguments made to the
`examiner can be understood in the contex1 of the application file. Of course, the applicant may desire to emphasize and fully
`describe those arguments which he or she feels were or might be persuasive to the examiner.)
`6) a general indication of any other pertinent matters discussed, and
`7) if appropriate, the general results or outcome of the interview unless already described in the Interview Summary Form completed by
`the examiner.
`
`Examiners are expected to carefully review the applicant's record of the substance of an interview. If the record is not complete and
`accurate, the examiner will give the applicant an ex1endable one month time period to correct the record .
`
`Examiner to Check for Accuracy
`
`If the claims are allowable for other reasons of record, the examiner should send a letter setting forth the examiner's version of the
`statement attributed to him or her. If the record is complete and accurate, the examiner should place the indication, "Interview Record OK" on the
`paper recording the substance of the interview along with the date and the examiner's initials.
`
`2
`
`
`340 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page 1of15
`
`FORM ~1449 US. DEPARTMENT OF COMMERCE
`PATENT AND nADEMARJ< OFFICE
`(REV. U3)
`INFORMATION DISCLOSURE OTA TION
`se several sheets if necusa
`
`APPLICANT
`A otex Inc.
`AUNGDATE
`2003
`
`APPLICATION SERIAL NO.
`1 11,814
`
`GROUP ART UNIT
`1614
`
`U.S. PATENT DOCUMENTS
`
`~R
`DOCUMENT NUMBER
`INITIAL
`
`DATE
`
`NAME
`
`CLASS
`
`SUBClA5.5
`
`RUNCDATE
`IF APPROPRIATE
`
`FOREGN PATENT DOCUMENTS
`
`DATE
`
`COUNTRY
`
`IRAN5LATION
`NO
`YES
`
`OTHER DOCUMENTS (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`Gabutti V, Piga A. Results of Long-Term Iron-Chelating Therapy. Acta Haematol 1996; 95:26-
`36.
`WoUe LC, Olivieri NF, Sallan D, Colan S, Rose V, Propper RD et al. Prevention of cardiac
`disease by subcutaneous desferrioxamine in patients with thalassemia major. N Engl J Med
`1985;312(25): 1600-1603.
`Aldouri MA, Wonke B. Hoffbrand AV, Flynn DM, Ward SE, Agnew JE et al. High Incidence
`of Cardiomyopathy in Beta-Thalassemia Patients Receiving Regular Transfusion and Iron
`Chelation: Reversal by Intensified Chelation. Acta Haematol 1990; 84:113-117.
`Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE et al. Efficacy
`of Desf errioxamine in Preventing Complications of Iron Overload in Patients with
`Thalassemia Major. N Enid J Med 1994; 331(9):567-573.
`Giardina PJV, Ehlers I<H, Engle MA, Grady RW, Hilgartner MW. The Effect of Subcutaneous
`Desferrioxamine on the Cardiac Profile of Thalassemia Major: A Five-Year Study. Ann NY
`Acad Sci 1985; 445:282-292.
`Borgna-Pignatti C, Rugologgo S, DeStefano P, Piga A, et al. Survival and Disease
`Complications in Thalassemia Major. Ann NY Acad Sci 1998; 850:227-231.
`
`I
`........
`
`~
`
`i(6'
`
`:/'7 //
`
`J
`
`DATE C'IDERED
`
`s 22-fal
`
`EXAM™ER
`
`---·-2 l
`
`.~
`EXAMllllER: ln.itial ii citation conside1ed, wl\e(her or not citation is in confdnnance'with MPEP fl»; Draw Une through citation ii
`not in confonnance and not considered. Include coov of this fonn with next commW1ication to aoolicant
`
`
`341 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page 2 of IS
`
`TION OF PRIOR ART
`
`I
`
`ATTY. OOCl<ET NO.
`PC-1834033
`APl'UCANT
`A otex Inc:.
`flUNCDATE
`003
`
`APPUCATION SERIAL NO.
`1 11,814
`
`CROUP ART UNIT
`1614
`
`U.S. PATENT DOCUMENTS
`
`EXAMINER
`INTTIAL
`
`DOCUMENT NUMBER
`
`DATE
`
`NAME
`
`CT.ASS
`
`SUBCLASS
`
`FIUNGDATE
`IF APPROPRJATE
`
`FOREIGN PATENT DOCUMENTS
`
`DATE
`
`COUNTRY
`
`TRANSLAJ]ON
`YES
`NO
`
`OTHER DOCUMENTS (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu P, McGee A et al. Survival in
`Medically Treated Patients with Homozygous Beta-Thalassemia. N Engl J Med 1994;
`331 9 :574-578.
`Addis A, Loebstein R, Koren G, Einarson TR. Meta-analytic review of the clinical
`effectiveness of oral deferi rone Deferi rone . Eur Clin Pharmacol 1999; 55:1-6.
`Grady RW, Hilgartner MW, Giardina PJV. Deferiprone: Its Effectiveness Relative to that of
`Desferrioxamine. 61h International Conference on Thalassemia and the Haemoglobinopathies,
`Abstract #2. 1997.
`Olivieri NF, Brittenham GM, Armstrong SAM, Basran RI<, Daneman R, Daneman N et al.
`First Prospective Randomized Trial of the Iron Chelators Deferiprone (Deferiprone) and
`Deferoxamine. Blood 86[10 Suppl. 1), 249a. 1995.
`
`EXAMINER
`
`DATE CONSIDERED
`
`~
`
`, whether or not citation is in co onnance with MPEP 609; Draw line through citation il
`EXAMINER: Initial if citation consid
`not in confonnance and not considered. Include co of this form with next communication to a
`licant.
`
`
`342 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page 3 of IS
`
`FORM pro.1449 US. OEP ARJMEllIT OF COMMERCE
`PATENT AND TRADEMARK OFACE
`(REV. 8-.'!3)
`INFORMATION DISCLOSURE CIT A Tl ON
`!Use several sheets if neceSArv)
`!CUSTOMER NO. 23607!
`
`ATTY. DOCKET NO.
`PC-1834033
`AP PU CANT
`Apotexlnc.
`FIUNGOATE
`--·----03
`
`I APPLICATION SERIAL NO.
`
`10/311,814
`
`I GROUP ART UNIT
`
`161'
`
`I
`I
`I
`
`EXAMINER
`INmAL
`
`DOCUMENT NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLA$
`
`FIUNGDATE
`IF APPROPRIATE
`
`U.S. PATENT DOCUMENTS
`
`FOREIGN PATENT DOCUMENTS
`
`DATE
`
`COUNTRY
`
`!RANSLATJON
`NO
`YES
`
`OTHER DOCUMENTS (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`Olivieri NF, Belluzzo N, Muraca M, MacKenzie CC, Milone S, Polsinelli K et al Evidence of
`Reduction in Hepatic, Cardiac and Pituitary Iron Stores in Patients with Thalassemia Major
`During Long-Term Therapy with the Orally Active Iron Chelating Agent Deferiprone. Blood
`I. 1 , 109a. 1994.
`84 10 Su
`Link G, Konijin AM, Hershko C. Cardioprotective effect of alpha-tocopherol, ascorbate,
`desferrioxamine, and deferiprone: mitochondrial function in cultured, iron-loaded heart cells.
`J Lab Clin Med 1999; 133: 179-188.
`De Franceschi L, Shalev 0 , Piga A, Collell M, Olivieri 0, Corrocher R et al. Deferiprone
`the.rapy in homozygous human beta-thalassemia removes erythrocyte membrane free iron
`and reduces KCI contrans ort activi
`. Lab Clin Med 1999; 133:64-69.
`Carthew P, Smith AG, Hider RC, Dorman B, Edwards RE, Francis JE. Potentiation of iron
`accumulation in cardiac myocytes during the treatment of iron overload in gerbils with the
`hydroxypridinone iron chelator CP94. Biometals 1994; 7:267-271.
`
`ormance with MPEP 609; Draw line through citation ii
`EXAMINER: Initial ii citation consid
`, whether or not citation i.9 in c
`not in confonnance and not considered. Include co of this fonn with next communication to a
`licant.
`
`
`343 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page 4of15
`
`CITATION OF PRIOR ART
`
`FORM PTG-1449 US. DEPARTMENT OF COMMERCE
`(REV. 8-$3)
`PATENr AND TRADEMARK OFFICE
`INFORMATION DISCLOSURE err A TION
`
`APPLICATION SERIAL NO.
`10
`t.814
`
`FJUNCDATE
`
`CROUP ART UNIT
`1614
`
`U.S. PATENT DOCUMENTS
`
`EXAMINER
`INTTIAL
`
`tXX:UMENT NUMBER
`
`DATE
`
`NAME
`
`a.ASS
`
`SUBCLASS
`
`FIUNGDATE
`IF APPROPRIATE
`
`FOREIGN PATENT DOCUMENTS
`
`1~~·1
`
`DATE
`
`COUNTRY
`
`TRANSLATION
`YES
`NO
`
`OTHER DOCUMENTS (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`Hider RC, Kayyli R, Evans P, Mackinnon S. The production of Hydroxyl RadicaJs by
`Deferi ron~iron com ounds under h siolo ical conditions. Blood 94 10, 406a. 1999.
`Engle MA, Erlandson M, Smith CH. Late Cardiac Complications of Chronic, Severe,
`Refracto Anemia with Hemochromatosis. Circulation 1964; 30:698-705.
`The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for
`Diagnosis of Disease of the heart and Great Vessels. 91!1 ed. Boston, Mass; Little, Brown & Co;
`1994:253-255.
`Sirchia G, Zanella A. A Short Guide to the Management of Thalassemia. Thalassemia Today:
`the Mediterranean Ex erience. 1987: 635-670.
`
`ered, whether or not citation is in cor\formanc:e with MPEP fHJ; Draw line through citation if
`not in conformance and not considered. Include co of this fonn with next colllD\unication to a
`licant.
`
`
`344 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page 5of15
`
`CITATION OF PRIOR ART
`
`FORM Pf(}.1449 US. OEPAR'Th<ENT OF COMMERCE
`PATENT AND'raADEMARK OFFICE
`(REV. U:l)
`INFORMATION DISCLOSURE OTA TI ON
`se several sheets ii necessa
`
`NO.
`
`APPUCATION SERIAL NO.
`1
`11,814
`
`CROUP ART UNIT
`1614
`
`EXAMINER
`INITIAL
`
`DOCUMEm' NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLASS
`
`FlUNGDATE
`IF APPROPRIATE
`
`U.S. PATENT DOCUMENTS
`
`I
`
`FOREIGN PATENT DOCUMENTS
`
`DATE
`
`COUNTRY
`
`TRANSi.ADON
`YES
`NO
`
`OTIIER DOCUMENTS (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`Hider RC, Kayyli R, Evans P, Mackinnon S. The production of Hydroxyl Radicals by
`Deferi rone-iron com ounds under h siolo ical conditions. Blood 94 10, 406a. 1999.
`Engle MA, Erlandson M, Smith CH. Late Cardiac Complications of Chronic, Severe,
`Refracto Anemia with Hemochromatosis. Circulation 1964; 30:693-705.
`The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for
`Diagnosis of Disease of the heart and Great Vessels. 9lh ed. Boston, Mass; Little, Brown & Co;
`1994:253-255.
`Sirchia G, Zanella A. A Short Guide to the Management of Thalassemia. Thalassemia Today:
`the Mediterranean Ex erience. 1987: 635-670.
`
`EXAMINER: Initial if citation considered., whether or not citation is in co ormance with MPEP (!;fl; Draw line through citation if
`not in conformance and not considered. Include co of this form with next communication to a
`licant.
`
`
`345 of 435
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1004
`
`

`

`Page6of 15
`
`CITATION OF PRIOR AR
`
`FORM PT~1449 U.S. DEPARTMENT OF COMMER
`(REV. S-83)
`PATENT ANDTRADEMARX OFFICE
`INFORMATION DISCLOSURE CIT ATJON
`Use several sheeis ii neces