Attorney Docket No. 13779-121
`
`Patent
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant: Hans ZIEGLER et a1.
`
`Mail Stop Amendment
`
`US. Patent Application Serial No.: 11/917,976
`
`Examiner: Yong Liang Chu
`
`Filing or 371(0) Date: December 18, 2007
`
`Group Art Unit: 1626
`
`Title: Crystalline Modifications to Pyraclostrobin
`
`Confirmation No.: 1966
`
`AMENDMENT
`
`Mail Stop Amendment
`Commissioner for Patents
`PO. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`In response to the Office Action mailed January 12, 2010, please amend this
`
`application as follows.
`
`Amendments to the Claims are reflected in the listing of claims which begins on
`
`page 2 of this paper.
`
`Remarks begin on page 5 of this paper.
`
`PETITIONER — WILLOWOOD USA, LLC
`EXHIBIT WW 1006
`
`

`

`Application No.: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Amendments to the Claims:
`
`Attorney Docket No. 13779-121
`Page 2 of 11
`
`This listing of claims will replace all prior versions, and listings, of claims in the application:
`
`Listing of Claims:
`
`Claim 1-21 (Cancelled).
`
`Claim 22 (Previously presented): A crystalline modification IV of pyraclostrobin
`
`which, in an X-ray powder diffractogram at 25°C, shows at least three of the following
`
`reflexes:
`
`d= 6.02 a: 0.01 A
`
`d = 4.78 a: 0.01 A
`
`d— 4.01 a: 0.01 A
`
`d = 3.55 a: 0.01 A
`
`d= 3.01 a: 0.01 A.
`
`Claim 23 (Previously presented): The crystalline modification IV according to claim
`
`22 having a melting point in the range from 62 to 72°C.
`
`Claim 24 (Previously presented): The crystalline modification IV according to claim
`
`22 having a pyraclostrobin content of at least 98% by weight.
`
`Claim 25 (Previously presented): A process for preparing a crystalline modification
`
`IV of pyraclostrobin according to any of the preceding claims, comprising:
`
`i)
`
`dissolving a pyraclostrobin form different from modification IV in an organic
`
`solvent or solvent mixture, where the organic solvent or solvent mixture comprises at least
`
`70% by volume of at least one fully water-miscible organic solvent L1 and up to 30% by
`
`volume of water; and
`
`ii)
`
`effecting crystallization of pyraclostrobin over a period of at least 10 hours
`
`and/or in the presence of seed crystals of modification IV.
`
`

`

`Application No.: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 3 of 11
`
`Claim 26 (Previously presented): The process according to claim 25, where the
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`pyraclostrobin is dissolved at a temperature above 50°C.
`
`Claim 27 (Previously presented): The process according to claim 26, wherein the
`
`solution is cooled to crystallize the pyraclostrobin.
`
`Claim 28 (Previously presented): The process according to claim 25, wherein the
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`crystallization of the pyraclostrobin is effected by adding water to the pyraclostrobin solution.
`
`Claim 29 (Previously presented): The process according to claim 25, wherein seed
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`crystals of modification IV are added during or prior to the crystallization of the
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`pyraclostrobin.
`
`Claim 30 (Previously presented): The process according to claim 25, where the fully
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`water—miscible organic solvent L1 is selected from C1-C4-alkanols, acetone and butanone.
`
`Claim 31 (Previously presented): The process according to claim 30, where, in step
`
`i), methanol, ethanol or a solvent mixture comprising at least 70% by volume of methanol
`
`and/or ethanol is used for dissolving the pyraclostrobin.
`
`Claim 32 (Previously presented): The process according to claim 25, wherein after a
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`partial amount of the pyraclostrobin is crystallized in the solution, water is added to bring the
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`crystallization of the pyraclostrobin to completion.
`
`Claim 33 (Previously presented): A process for preparing a crystalline modification
`
`IV of pyraclostrobin according to claim 22, comprising:
`
`i)
`
`preparing a suspension of a pyraclostrobin form different from modification
`
`IV in an organic solvent;
`
`ii)
`
`optionally, adding seed crystals of modification IV to the suspension;
`
`

`

`Application No: l l/9l7,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. [3779-121
`Page 4 of 11
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`iii)
`
`agitating the suspension until at least 90% of the pyraclostrobin comprised
`
`therein is present in the form of modification IV.
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`Claim 34 (Previously presented): The process according to claim 33, where the
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`organic solvent used in step i) to suspend the pyraclostrobin compriSes at least 50% by
`
`volume of at least one C1-C4-alkanol.
`
`Claim 35 (Previously presented): The process according to claim 34, where the
`
`organic solvent used in step i) to suspend the pyraclostrobin comprises at least 70% by
`
`volume of methanol, isopropanol and/or ethanol.
`
`Claims 36-39 (Cancelled).
`
`Claim 40 (Cuirentiy amended): A composition for crop protection, comprising
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`pyraclostrobin in the form of medifieatien—I—I; modification IV, carriers, and/or auxiliaries.
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`Claim 41 (Previously presented): The composition according to claim 40 in the form
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`of an aqueous suspension concentrate.
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`Claim 42 (Currently amended): A method for controlling phytopathogenic fungi
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`comprising contacting a plant, seed, or soil in need of treatment with a crystalline form of
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`modification H—er IV of pyraclostrobin.
`
`

`

`Application No: l 1/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 5 of 11
`
`REMARKS
`
`Claims 22-35 and 40-42 are pending in the present application. Claims 40 and 42
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`have been amended to remove recitation of crystal modification II. Claims 36-39 have been
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`cancelled without prejudice to or disclaimer of the subject matter contained therein.
`
`Reexamination of the application and reconsideration of the rejections and objections
`
`are respectfully requested in view of the above amendments and the following remarks,
`which follow the order set forth in the Office Action.
`
`Preliminary Matters
`
`Applicants acknowledge and thank the Examiner for withdrawing the restriction
`
`requirement.
`
`Rejections under 35 U.S.C. §§ 102(b)/103(a)
`
`The office action rejected claims 22-42 under 35 U.S.C. §102(b), as being anticipated
`
`by, or 35 U.S.C. §103(a) as obvious over US. Patent Application No. 2003/0199394 (“the
`
`‘394 application”) allegedly because the ‘394 application discloses
`
`crystallines of pyraclostrobin in TABLES 1-2, column 7, a
`composition comprising a compound thereof, a process for making
`the compound, and a method of using the compound for
`controlling phytopathogenic fungi. The process taught here is the
`same process used for making the instantly claimed crystalline
`modification II and IV of pyraclostrobin.
`
`Office Action, pages 3-4. Applicants respectfully traverse the rejection.
`
`The amended claims recite crystalline modification IV of pyraclostrobin, a process for
`
`making the same, a composition comprising the same and a method for controlling
`
`phytopathogenic fungi comprising contacting a plant, seed, or soil in need of treatment with
`
`the same. Contrary to the office action’s assertion, the ‘394 application does not disclose
`
`crystalline modification IV of pyraclostrobin or a process of making it. Rather, the
`
`pyraclostrobin crystals disclosed in the ‘3 94 application are pyraclostrobin modification I as
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`defined in the specification of the present application and modification I is not presently
`
`claimed.
`
`First, comparison of the process in the '3 94 application for preparing the crystalline
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`material disclosed with the process used for preparing modification I of pyraclostrobin
`
`described in the specification of the present application reveals that the pyraclostrobin
`
`crystalline material described in the '394 application is modification I. The '3 94 application
`
`

`

`Application No.: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 6 of 11
`
`teaches a process for purifying a pesticide, e. g. pyraclostrobin, including the steps of melting
`
`the pesticide that contains a crystallization inhibitor, coating a carrier with the resulting melt
`
`in order to form active agent particles and afterwards removing the impurity by azeotropic
`
`distillation. Cooling the molten pesticide below its melting point initiates the crystallization
`
`of the pesticide. The office action acknowledges that
`
`the ‘394 application teaches a process wherein Batch 1A and 1B
`were melted at about 80 °C, and allowed to crystallize for 1 week
`at temperatures of 25 °C and 50 °C,”
`
`Office action, page 4. Consistent with the ‘394 application, crystal modification I of the
`
`present application is obtained by melt-crystallization. According to the specification of the
`
`present application:
`
`Modification 1 of pyraclostrobin is typically obtained on cooling of
`a pyracIOStrobin melt when the purity of the pyraclostrobin used
`for preparing the melt is at least 95%. By tempering the material at
`temperatures in the range from 40 to 50°C, crystallization of
`modification I can be accelerated.
`
`Specification, page 11, lines 32-35. Moreover, Example 5 (page 27 of the specification)
`
`provides a method of preparing pyraclostrobin modification I by crystallization of molten
`
`pyraclostrobin. In each of the processes described in the ‘394 application and the process
`
`described in the specification of the present application for preparing modification I of
`
`pyraclostrobin, pyraclostrobin crystallizes during the cooling of the melt. Thus, the process
`
`described in the ‘394 application generates modification I of pyraclostrobin, which has the
`
`X—ray powder diffractogram shown in Fig. 3 of the present application.
`
`In contrast to the process used to prepare modification I both in the ‘394 application
`
`and in the present application, modification IV is prepared using a solution—recrystallization
`
`process. According to the specification of the present application:
`
`The crystalline modification IV of pyraclostrobin can be prepared
`using a process (hereinbelow also referred to as process IVa),
`which comprises the following steps:
`i)
`dissolving a pyraclostrobin form different from modification
`IV in an organic solvent or solvent mixture, where the organic
`solvent or solvent mixture comprises at least 70% by volume
`of at least one fully water—miscible organic solvent L1 and if
`appropriate up to 30% by volume of water; and
`effecting crystallization of pyraclostrobin over a period of at
`least 10 h, in particular at least 15 h and especially at least 20
`h and/or in the presence of seed crystals of modification IV.
`
`ii)
`
`

`

`Application No.: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 7 of 11
`
`Specification, page 3, lines 7-15. Additional preparation processes for modification IV are
`
`described in pages 8-9, and in Examples 1-3, and 7-9 of the specification of the present
`
`application. Because of the inherent difference between solution-recrystallization and melt-
`
`crystallization, there is no reason to believe that the crystal modification obtained from the
`
`solution-recrystallization would be the same crystal modification as the modification obtained
`
`for a melt crystallization process. Indeed, crystal modification I obtained from the melt-
`
`crystallization has a melting point in the range from 55-56°C (see specification, page 11, lines
`
`28-30) whereas modification IV obtained from the solution-recrystallization has a melting
`
`point in the range of 65-67°C (see'specification, page 2, lines 14-16). Furthermore, crystal
`
`modification I obtained from the melt-crystallization exhibits an X-ray diffraction pattern
`
`(Figure 3) that is different from that exhibited by modification IV (Figure l) of the present
`
`application. Thus, it is clear that the ‘394 application discloses crystal modification I and not
`
`crystal modification IV.
`
`Moreover, although the ‘394 application does not provide many of the physical
`
`properties of the crystalline pyraclostrobin disclosed therein, the enthalpy of fusion disclosed
`
`therein is consistent with crystal modification I and not with modification IV. According to
`the ‘394 application, the enthalpy of fusion of the crystalline pyraclostrobin is 61.13 j/g. . See
`the ‘394 application, paragraph [0063]. The specification of the present application discloses
`
`four crystal modifications pyraclostrobin and their enthalpies of fusion:
`
`1. modification I, having enthalpy of fusion of 63-65 j/g (see page 11, lines 15-30 of
`
`the specification);
`
`2. modification II, having an enthalpy of fusion of 67-70 j/g (see page 11, line 39
`
`through page 12, line 17);
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`3. modification III, having enthalpy of fusion of 69-72 j/g (specification, page 13,
`line 36 through page 14, line 8); and
`Q
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`4. modification IV, having enthalpy of fusion of 72-78 j/g (specification page 2,
`
`lines 4-20).
`
`Thus, the enthalpy of fusion of the crystal modification disclosed in the ‘394 application of
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`61.13 j/g is also mostly consistent with crystalline modification I above.
`
`For the forgoing reasons, the ‘394 application does not anticipate the claims of the
`
`present application. Accordingly, applicants respectfully request that the rejection be
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`withdrawn.
`
`

`

`Application No.: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 8 of 11
`
`The office action further alleges that “[t]he solvent(s) used for making the instantly
`
`claimed pyraclostrobin crystallines was taught by the prior art and/or is “obvious to try” for
`
`one skilled in the art.” Office action, page 4. Applicants disagree.
`
`First, the ‘394 application does not provide a method for crystallizing pyraclostrobin
`
`from a solvent system. Rather, it provides a method in which a pesticide that contains an
`
`impurity that inhibits crystallization is first melted, then molten pesticide is coated on a
`
`substrate to form a pesticide particle, followed by reduction of the impurity by an azeotropic
`
`method and finally crystallizing the pesticide by keeping the molten pesticide at a temperature
`
`below its melting point. Indeed, in all samples examined in the ‘394 application, molten
`
`compound was kept at a temperature low enough for crystallization. Only crystal
`
`modification I is accessible from melt crystallization. There is no teaching, suggestion or
`
`even an indication anywhere in the ‘394 application that pyraclostrobin can be crystallized
`
`from a solution to produce a crystal modification different from that produced from melt
`
`crystallization. Moreover, the skilled artisan is not even motivated to discover new crystal
`
`forms using solvent recrystallization because there was no evidence that the compound can
`
`exist in more than one crystal form.
`
`Moreover, the “obvious to try” standard requires the existence of finite solutions from
`
`which the skilled artisan can choose. Here, there are a great number of variables that could
`
`have an impact on the crystalline form obtained. Because the existence of the modification
`
`claimed in the present application was not even known in the art, no solution can exist to
`
`make that which is not known. Therefore, the ‘394 application does not render the claimed
`
`modification IV of pyraclostrobin obvious.
`
`Even if, arguendo, the Examiner had made the prime facie case, SUSpension
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`concentrates prepared using crystalline modification IV show superior storage stabilities than
`
`comparable suspension concentrates prepared from modification I as disclosed in the ‘394
`
`application. In this connection, comparative formulation example in page 29 is compared to
`
`formulation example 1 on page 30.
`
`In the comparative formulation on page 29 molten
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`pyraclostrobin material was coated on a carrier in the presence of a wetting agent according to
`
`the directions in the ‘394 application. This approach corresponds to the process described on
`
`page 2, paragraphs 0033-0036 of the ‘394 application. The obtained material (after azeotropic
`
`separation, removal of impurities and crystallization of the melt) is subsequently used to
`
`prepare an aqueous suspension c0ncentrate. Thus, the comparative example on page 29
`
`

`

`Application No: 11/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 9 of 11
`
`represents the closest prior art. Formulation example 1 on page 30 was prepared using
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`pyraclostrobin of modification IV.
`
`Data for storage stability for the two formulations is shown in Table 3 (page 31 of the
`
`specification). From these examples it is clear that modification IV provides for more stable
`
`formulations than the material obtained from the process of the '394 application.
`
`By comparing the storage stabilities of the comparative formulation according to the
`
`‘394 application with the one of the formulation example 1, it becomes evident that the use of
`
`crystalline modification IV provides for an aqueous suspension concentrate with enhanced
`
`storage stability. In particular, in contrast to the comparative formulation, no significant
`
`increase in the maximal particle size was observed. Thus, compared to the pyraclostrobin
`
`according to the '394 application, the crystalline modification IV of pyraclostrobin exhibits an
`
`unexpected benefit. Thus, even if we assume that the office action made the prima facie case
`
`of obviousness, the comparative data shows an unexpectedly superior stability associated to
`
`modification IV as compared to modification 1. Accordingly, the ‘394 application does not
`
`render modification IV obvious.
`
`The office action further alleges that because a compound and its pr0perties are
`
`inseparable, the skilled artisan would reasonably assume that the compounds of the ‘394
`
`application would share the X-ray diffraction properties of the claimed modification.
`
`Applicants disagree.
`
`As shown in the specification of the present application, modification I and
`
`modification IV of pyraclostrobin exhibit different physical properties as well as different
`
`X-ray diffraction properties. It is known in the art that two crystal modifications of a
`
`compound can and often have distinctive X-ray diffraction patterns as well as different
`
`physical properties. Indeed, it is the very existence of the different X-ray diffraction patterns
`
`that provides evidence for the existence of the different crystal modifications of the same
`
`compound. Therefore, this assertion has no factual basis.
`
`For the forgoing reasons, the crystal modification described in the ‘394 application is
`
`different from the crystal modification recited in the claims of the present application. As
`
`such, applicants assert that the ‘394 application does not anticipate or render obvious the
`
`claims of the present application.
`
`

`

`Application No.: l 1/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 10 of 11
`
`Rejections under 35 US. C. §112, First Paragraph
`
`The office action rejected claims 24, 33, and 38 under 35 U.S.C. § 112, first
`
`paragraph, allegedly as failing to comply with the Written Description Requirement.
`
`According to the Examiner, “the claims define crystalline pyraclostrobin content of at least
`
`98%, or 90% by weight.” Office action, page 5. Applicants traverse this rejection.
`
`Applicants note that there are many known methods in the art that the skilled artisan
`
`can use to determine the purity of a particular crystal modification. For example, calorimetric
`
`methods may be used to determine the purity of a particular sample by analyzing the DSC
`
`melting peak shape and melting temperature of the impure crystal modification and
`
`comparing it to data collected from a known pure sample. See, for example, the 1984
`
`Symposium on “Purity Determinations by Thermal Methods,” R. L. Blaine and C. K. Schoff,
`
`eds., pages 5-15 (enclosed with this reply as Exhibit A). Thus, once the skilled altisan
`
`knows the particular modification, it only takes little experimentation to determine what the
`
`purity of that crystal form is. Moreover, Applicants have described in the specification of the
`
`present application pyraclostrobin crystal modification IV having various contents of the
`
`modification as can be determined from DSC analysis. For example, “[t]he amount of
`
`modification IV, based on the total amount of pyraclostrobin, is typically at least 90%,
`
`frequently at least 95% and in particular at least 98%.” Specification, page 11, lines 3-4.
`
`Thus, Applicants clearly had possession of pyraclostrobin crystal modification IV having
`
`varying contents of impurities depending on the purity of the starting material. Therefore, the
`
`specification of the present application complies with the Written Description and
`
`Enablement requirements of 35 U.S.C. § 112, first paragraph. Accordingly, withdrawal of
`
`the rejection is respectfully requested.
`
`For the foregoing reasons, claims 22-35 and 40-42 are considered allowable. A
`
`Notice to this effect is respectfully requested. If any questions remain, the Examiner is
`
`invited to contact the undersigned at the number given below.
`
`10
`
`

`

`Application No.: l l/917,976
`Amdt. Dated: April 23, 2010
`Reply to Office Action Dated: January 12, 2010
`
`Attorney Docket No. 13779-121
`Page 11 of 11
`
`The Director is hereby authorized to charge any appropriate fees that may be required
`
`by this paper, and to credit any overpayment, to Deposit Account No. 23-1925.
`
`Respectfully submitted,
`
`BRINKS HOFER GILSON & LIONE
`
`1W
`
`Bashir M. Ali
`
`Registration No. 47,939
`
`Date: April 23, 2010
`
`By:
`
`2801 Slater Road, Suite 120
`Morrisville, NC 27560-8477
`Phone: 919.481.1111
`759942v1
`
`Attachment: Exhibit A
`
`11
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`