IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re application of: Rajiv Singh et al.
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`Examiner: Amina Khan
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`Application No.:
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`12/412,342
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`Group Art Unit: 1796
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`Filed:
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`March 26, 2009
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`Docket No.: H0003965DIVlB
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`Title: Compositions Containing Fluorine Substituted Olefins and Methods and
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`Systems Using Same
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`Commissioner for Patents
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`Alexandria, VA 22313-1450
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`RULE 132 DECLARATION OF DOCTOR GEORGE RQSCH
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`I, Dr. George Rusch, declare and state that:
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`2.
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`I am the Director of Toxicology and Risk Assessment at Honeywell International Inc.
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`(“Honeywell"). Ihold a PhD. degree in Chemistry from Adelphi University, in
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`Garden City, NY. I have been employed by Honeywell and/or its predecessor in '
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`interest, the assignee of the application, since about August, 1980 holding various
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`positions, including my current position as Director of Toxicology and Risk
`Assessment.
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`Toxicological testing of HFO-1225zc (1,1.3.3.3-pentafluoropropene)
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`F3C
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`HFO l225zc
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`is described in the U.S. Department of Commerce, National Technical Information
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`Service publication entitled “Support: Letter from Dupont Haskell Lab to US EPA
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`Regarding Results of Bacterial Reverse Mutation Assay Conducted with l-Propene,
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`l,l,3,3,3,-Pentafluoro-, dated 04/ 17/00" (Exhibit “A”). The toxicity tests were conducted
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`by standard methods known to those of ordinary skill in the art. In particular, the
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`PH1 %69459vl 07/28/10
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`Page 1 of 5
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`Arkema Exhibit 1145
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`Page 1 of 5
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`Arkema Exhibit 1145
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`Application No. 12/412,342
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`Attorney Docket No. Hooo396sDIv1B
`Page 2 of 5
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`methods involve determining the LC5o or median lethal concentration required to kill half
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`the members of a tested population. The protocol used for this LC5o study consisted of a
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`series of separate 4-hour exposures of groups of rats to the test compound. The animals
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`are observed for mortality that may occur during the exposure or within the 14 day post-
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`exposure observation period. Results of this test are reported in Table 1 below.
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`Table 1
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`”°’°“"""’
`*At 2000 ppm, more than half (6/10) of the rats died.
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`2,000‘
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`I have tested and/or supervised toxicological testing of HFO- l234yf (2.3,3,3-
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`tetrafluoropropene):
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`CF;-CF=Cl-I2
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`The HFO—l234yf testing done by me and/or under my supervision used substantially the
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`same methods used to produce the results described in connection with the published testing
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`of I-IFO-l225zc described above, except that a greater initial population was used in testing
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`l-IFO-l225zc. Honeywell uses small population sizes in toxicity testing where possible to
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`minimize the use of animals in its testing programs. Results of the HFO-l234yf testing that
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`was done by us, and which we believe to be reliable and representative of results comparable
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`to the test results reported in Exhibit A., are reported in Table 2.
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`"
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`PHI 2569459vl 07/28/10
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`Page 2 of 5
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`Concentration (ppm)
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`Population Deaths after Exposure
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`Population Survival
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`medmsawm 12
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`Application No. 12/412,342
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`Attorney Docket No. H0003965DIV1B
`Page 3 of 5
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`c°~°=~m<»m>
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`Table 2
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`:1
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`400.000
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`The results in Table 2 illustrate that HFO-1234yf is far less toxic than HFO-1 225m.
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`In particular this information is evidence that I-IFO-1234yf has a toxicity, as measured by
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`LC5o,at least approximately 200 times less than HFO-l225zc.
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`I have tested and/or supervised toxicological testing of transl-IFO-l234ze
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`(transl,3,3,3-tetrafluoropropene):
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`CF;-CH=CFH
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`The transl-IFO-1234ze testing done by me and/or under my supervision used substantially the
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`same methods used to produce the results described in connection with the published testing
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`of I-IFO-1225zc described above, except that a greater initial population was used in testing
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`I-IFO-l225zc. As mentioned above. Honeywell uses small population sizes in toxicity testing
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`where possible to minimize the use of animals in its testing programs. Results of the
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`transHFO-l234ze testing that was done by us, and which we believe to be reliable and
`representative of results comparable to the test results reported in Exhibit A., are reported in
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`Table 3.
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`°°“°°"""‘°“‘*""“’
`Initial Population Size (rats)
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`Table 3
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`3 W gmup
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`PHI 2569-159vl 07/28/10
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`Page 3 of 5
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`Attorney Docket No. H0003965DIVlB
`Page 4 of 5
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`Application No. 12/412,342
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`transHFO l234ze
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`3 wM
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`200,000
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`6.
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`The results in Table 3 illustrate that transl-IFO-1234ze is far less toxic than HFO-
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`1225zc. In particular this information is evidence that tansl-IFO-1234ze has a toxicity, as
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`measured by LC5o , at least approximately 100 times less than I-IFO—1225zc.
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`7.
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`I have tested and/or supervised toxicological testing of transHFO-1233zd (trans-1-
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`chloro-3,3,3-trifluoropropene):
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`CF;-CH=CC1H
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`The transHFO-1233zd testing done by me and/or under my supervision used substantially the
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`same methods used to produce the results described in connection with the published testing
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`of I-IFO-l225zc described above, except that a greater initial population was ,,used in testing
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`HFO-1225zc. Honeywell uses small population sizes in toxicity testing where possible to
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`minimize the use of animals in its testing programs. Results of the HFO-l233zd testing that
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`was done by us, and which we believe to be reliable and representative of results comparable
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`to the test results reported in Exhibit A., are reported in Table 4.
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`Table 4
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`4-hr LC5o
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`Males: 1 l 8,200 ppm
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`Females: 121,700 ppm
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`4-hr LC” (both sexes combined)
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`120 000 ppm
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`8.
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`The results in Table 4 illustrate that transHFO-1233zd is far less toxic than HFO-
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`1225zc. In particular this information is evidence that transl-IFO-l233zd has a toxicity, as
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`measured by LC5o , that is at least 50 times less than HFO-1225zc.
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`PHI 2569459vl 07/28/10
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`Page 4 of 5
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`Page 4 of 5
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`Application No. 12/412,342
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`Attorney Docket No. H0003965DIVlB
`Page 5 of 5
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`9.
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`I hereby declare that all statements made herein of my knowledge are true and that _all
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`statements made on information and belief are believed to be true and further that the
`statements were made with the knowledge that willful false statements and the like so made
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`are punishable by fine or imprisonment, or both, under §100l of Title 18 of the United States
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`Code and that such willful false statements may jeopardize the validity of the application or
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`any patent 'ssued thereon.
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`Date
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`an/:1 Q5, 2010
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`PHI 25694S9Vl 07f28/10
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`Page 5 of 5