DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application filed on 12/21/2023, claims priority to EP23161577.4 filed 03/13/2023, and U.S. Provisional Application No. 63/476,661 filed on 12/22/2022.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 02/13/2026, 03/19/2026, 08/06/2026, 08/19/2026, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Election/Restriction
Applicant’s response filed on 04/07/2026 to Restriction/Election Requirement filed on 02/27/2026, is acknowledged. Applicant elected without traverse Group I drawn to a crystalline form of Compound A and a pharmaceutical composition comprising the crystalline form according to claim 1 and at least one pharmaceutically acceptable excipient. Claims 1-9, 17-28, and 37-40 read on the elected Group. Claims 10-14, 15-16, 29-30 and 31-36 of Group II, III, IV and V are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Thus, claims 1-36 are pending with claims 10-16 and 29-36 are withdrawn, and claims 1-9 and 17-28 are currently under consideration.
Status of claims
Applicants’ amendments and arguments filed on 08/05/2026 have been received and have been carefully considered.
Claims 16-17, 19, 30-36 were amended and claims 37-40 were canceled.
Claims 1-36 are pending. Claims 10-16 and 29-36 are withdrawn. Claims 1-9 and 17-28 are currently under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation of crystal form of compound A:
Claim 1 recites “… Compound A) in crystalline form, characterized by having an X-ray powder diffractogram comprising a reflection at 2-theta angles in the range of from 4.00 to 4.60 when measured at a temperature in the range of from 20 to 30°C with Cu-Ka radiation having a wavelength of 0.15406 nm. ° Claims 2-9 further recite spectroscopic characterization.
The instant specification defines the crystalline form of compound A as:
“The crystalline materials of the present invention were found to be physically and chemically stable against temperature and humidity stress. E.g. the crystalline form of Compound A obtained according to the procedure of Example 1 was stable when subjected to accelerated stress conditions of 40°C/75% relative humidity for 6 months. form A. [page 3, line 5-8]. Figure 1: illustrates the XRPD of the crystalline form of Compound A of the present invention obtained from the solvent system IPA/H20 according to Example 1 herein. The x-axis shows the scattering angle in °2-theta, the y-axis shows the intensity of the scattered X-ray beam in counts of detected photons. [page 9, ln. 29- page 10, ln. 2].
The instant specification also recites:
A solid-state form of Compound A may be referred to herein as being characterized by graphical data "as shown in" a figure. Such data include, for example, XRPDs, ssNMR spectra, FTIR spectra, Raman spectra, DSCs, TGAs and GMS isotherms. The person skilled in the art understands that factors such as variations in instrument type, response and variations in sample directionality, sample concentration, sample purity, sample history and sample preparation may lead to variations for such data when presented in graphical form, for example variations relating to the exact peak positions and intensities. [page 7, ln. 13-21].
The art teaches that compounds can exists in multiple crystalline forms, and the gold standard to distinguish these forms is through XRPD. The XRPD consider to be the fingerprint in determining and identifying the particular crystalline form. In view of the instant specification, the claimed crystalline form of compound A is defined by XRPD peaks as shown in Figure 1, and in view of the art, the crystalline form of compound A is defined by Figure 1 and will be interpreted as the crystal form of Figure 1.
The claims are given their broadest reasonable interpretation in light of the specification. MPEP 2111. In particular, the reference to “Crystalline Form of compound A” in the instant specification and in the claims is always associated with the language “comprising” and “characterized by” regarding spectroscopic information i.e., XRPD peaks. Consistent with MPEP 2111.03, the claims are construed as being open-ended to allowing additional elements (“comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps). In this case, the claims are construed as allowing other spectroscopic information as well as other solid forms “characterized” by additional information.
However, in view of the above interpretation, crystalline form of compound A is not defined by the “open-ended” claims 1-9 and the recited XRPD peaks, instead, the crystalline form of compound A is defined by Figure 1.
Claim interpretation for “predetermined amount/effective amount
Claim 23 and 24 recite “the pharmaceutical composition according to claim18 comprising a predetermined and/or effective amount of said crystalline form.” The instant specification described the predetermined and effective amount as:
"A predetermined amount" as used herein with regard to Compound A, or a pharmaceutically acceptable salt thereof, or a crystalline form thereof, refers to the initial amount of Compound A, a pharmaceutically acceptable salt thereof, or a crystalline form thereof, used for the preparation of a pharmaceutical composition having a desired dosage strength of Compound A. The term "effective amount" as used herein with regard to Compound A, a pharmaceutically acceptable salt thereof, or a crystalline form thereof, encompasses an amount of Compound A, or a pharmaceutically acceptable salt thereof, or a crystalline form thereof, which causes the desired therapeutic and/or prophylactic effect. [page 7, ln. 25]. In one embodiment, the predetermined and/or effective amount may be in the range of from about 1 to 200 mg, preferably of from about 5 to 100 mg, and most preferably of from about 10 to 60 mg, such as from about 10 to 45 mg, calculated as free Compound A. For example, the predetermined and/or effective amount is selected from the group consisting of 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg and 200 mg, calculated as free Compound A. In a preferred embodiment, the predetermined and/or effective amount is selected from the group consisting of 1 mg, 5 mg, 10 mg, 30 mg, 45 mg, 50 mg and 60 mg, calculated as free Compound A. In a particularly preferred embodiment, the predetermined and/or effective amount is selected from the group consisting of 10 mg, 30 mg and 45 mg, calculated as free Compound A. Most preferably, the predetermined and/or effective amount is 30 mg or 45 mg, calculated as free Compound A. [page 47].
Thus, the terms “predetermined” and “effective amount” will be interpreted consistent with the specification.
Response to Arguments
Applicant argues:
As noted in the Office Action, XRPD is considered to be the fingerprint in determining and identifying a particular crystalline form of a compound. However, this does not mean that a single X-ray powder diffractogram (e.g., as depicted in FIG. 1) can only define the crystalline compound. Instead, the "fingerprint" is determined by location of identified peaks (number of counts) in the X-ray powder diffractogram which are common in any X-ray powder diffractogram (subject to the same conditions for obtaining the data, namely, specified reflection, temperature range, radiation and wavelength of the XRPD) for the crystalline compound. Applicant further submits that a person having ordinary skill in the art (PHOSITA) would clearly recognize, understand and appreciate how to determine whether a crystalline form of compound A meets the claims based upon the recited particulars of the X-ray powder diffractogram (i.e., the particular reflection, temperature range, radiation and wavelength as recited in the claims). While Figure 1 provides an example embodiment of an X-ray powder diffractogram of compound A as claimed, the claimed compound A is not limited to the specific X-ray powder diffractogram depicted in FIG. 1. For example, and as clearly noted in the Specification, each of FIGS. 1-7 depicts an XPRD (X-ray powder diffractogram) of the crystalline form of compound A of the invention (and as recited in the claims), where each XPRD is a separate plot of data for the crystalline form of compound A obtained from different methods (e.g., different solvent systems were used) yet each XPRD still defines a reflection at 2-theta angles in a specified range (e.g., from 4.00 to 4.60 as recited in claim 1, from 9.20 to 9.60 as recited in claim 2, etc.) when measured at a temperature in the range of from 20 to 30°C with Cu-Kalpha radiation having a wavelength of 0.15406 nm. While each XPRD differs slightly (i.e., is not identical) with the other XPRD of FIGS. 1-7, they each meet the requirements for the definition of the crystalline form of compound A as recited in the claims.
Examiner response:
Applicant argues that while Figure 1 represents the claimed crystalline form, the claimed crystalline form should not be limited to only Figure 1 due to the possible shift in peaks by temperature changes, experimental conditions changes, etc. The Examiner agrees with Applicant that experimental conditions shift would slightly shift the XRPD peaks. The XRPD of Figure 1 determine and identify the claimed crystalline form. The XRPD peaks as shown in Figure 1, although skilled artisan would understand that slight shift is possible and acceptable, the crystalline form of compound A is defined by Figure 1 and will be interpreted as the crystal form of Figure 1.
Withdrawn Abstract Objection
Objection to the Abstract for improper language, is withdrawn in view of applicant amendment to the Abstract filed on 08/05/2026.
Withdrawn Claim Rejections - 35 USC § 101
Rejection to claim 17 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter for reciting “use of the crystalline form according to claim 1”, is withdrawn in view of applicant amendment filed on 08/05/2026 that amended claim 17 by deleting “use of …”.
Withdrawn Claim Rejections - 35 USC § 112(b)
Rejection to claim 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting “use of the crystalline form according to claim 1 for the preparation of a pharmaceutical composition”, without reciting the steps of using the process, is withdrawn in view of applicant amendment filed on 08/05/2026 that amended claim 17 by deleting “use of …”.
Rejection to claim 40 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn in view of applicant amendment filed on 08/05/2026 that canceled claim 40.
Rejection Maintained
Note: The 103 Rejection below is maintained. The Cornillie reference is removed in view of Applicant ‘s persuasive argument that Cornillie does not disclose the chemical structure of BI907828, and that the structure of BI907828 was disclosed after the effective filed date of instantly claimed invention. The rejection below is not considered a new grounds of rejection according to MPEP 1207.03 II. The MPEP states, “If the examiner’s answer removes one or more references from the statement of rejection under 35 U.S.C. 103 and relies on the same teachings of the remaining references to support the 35 U.S.C. 103 rejection, then the rejection does not constitute a new ground of rejection. For example, in In re Kronig, 539 F.2d 1300, 1302, 190 USPQ 425, 427 (CCPA 1976), the examiner rejected the claims under 35 U.S.C.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
§ 103 Rejection over Rudolph in view of Barth and Morissette
Claims 1-9, 17-19, and 21-28 are rejected under 35 U.S.C. 103 as being obvious over D. Rudolph et al. (US PG PUB 2020/0101079A1, 04/02/2020, “Rudolph” cited in the PTO-892 dated 05/29/2026) in view of W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 05/29/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 05/29/2026).
Joint Inventorship
This application currently names joint assignee. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Rudolph teaches MDM2 inhibitors for treating cancer, wherein MDM2 inhibitors including MDM2 inhibitor 28, [[0015], [0082], Table 1, comp. 28, and claim 3]:
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Rudolph teaches that the term “MDM2 inhibitor” as used herein also includes the MDM2 inhibitor in all its solid, preferably crystalline forms and in all the crystalline forms of its pharmaceutically acceptable salts, hydrates and solvates, [0083]. However, Rudolph does not specifically teach the claimed crystalline form of Rudolph’s compound 28 or the spectroscopic characterization.
In the same art area, namely pharmaceutical preparations and their use in treating disease, Barth teaches the following:
“[c]rystalline forms of compounds are ordinarily preferable to the non-crystalline forms thereof. The crystalline materials have superior stability, appearance and handling characteristics when compared to their amorphous counterparts. For pharmaceutical use crystalline compounds are especially advantageous in manufacturing procedures and in formation and use of acceptable dosage forms such as solutions, suspensions, elixirs, tablets, capsules and various pharmaceutically elegant preparations required by the medical and pharmaceutical professions.” [Pg. 2, col. 1, ln. 60- col. 2, ln. 2].
Morissette teaches an automated high-throughput crystallization to form polymorphs, salts, co-crystals and solvate forms of pharmaceuticals [Title, abstract]. The prior art describes the successful application of the automated high-throughput technique to several known pharmaceuticals and details how thousands of crystallization conditions can be performed in parallel, computer analyzed and then used to produce the polymorphic forms of a given pharmaceutical [Page 296, para. 2].
At the time of invention, one of ordinary skill in the art would have been motivated to prepare crystalline forms of the Rudolph’s pharmaceutical compound MDM2 inhibitor compound 28 because Rudolph teaches that the MDM2 inhibitors including compound 28 are anti-cancer and anti-tumor agents, Barth teaches that crystalline forms are preferred over non-crystalline forms; have superior stability; are preferred in formulation of dosage forms; and are advantageous in manufacturing procedures. [page 2, col. 1, ln. 60- col. 2, ln. 2].
One of ordinary skill in the art practicing Rudolph’s pharmaceutical compound 28 would form a crystalline form in accordance with the specific teaching of Rudolph. Utilizing the routine “High-throughput salt selection” taught by Morissette [page 285-287] one of ordinary skill in the art would arrive at the claimed invention. Specifically, because Rudolph teaches that crystalline forms of the MDM2 inhibitors, i.e., compound 28 are preferred. Thus, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention.
In the instant case one of ordinary skill in the art would have a reasonable expectation of success in following the teaching of Rudolph and utilizing the well-known and routine automated high-throughput screening described by Morissette arrive at the claimed invention because such acts are conventional and routine in the art. One of ordinary skill in the art would be expected to apply methods within their technical grasp (such as automated high-throughput screening) to improve that which is already known in the art. The Supreme Court stated in KSR “if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill.” KSR Intern. Co. v. Teleflex Inc., 127 S.Ct. 1727, 1731 (2007). Here, the use of an automated system to screen a pharmaceutical salt for crystallization is well known and specifically taught by Morissette. Therefore, the method is within the technical grasp of those of ordinary skill in the art and it would be obvious to one of ordinary skill in the art to use the same method and apply it to Rudolph’s compound 28.
Regarding the spectroscopic characterization of the obvious product, such properties are inherent in the product (MPEP 2112.02: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.). In this case, one of ordinary skill in the art would have reasonably considered producing the crystalline salt form which would inherently show the same spectroscopic parameters as are in the claim. "[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, or ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977).
Thus, claims 1-9 are rejected as prima facie obvious.
With regard to claim 17-19, 21-22 and 25-28, Rudolph teaches a pharmaceutical composition or dosage form comprising an MDM2 inhibitor i.e., compound 28, and one or more pharmaceutically acceptable carriers, excipients and/or vehicles, [0030], [0133], wherein the pharmaceutical composition is tablets prepared with excipients including diluents, disintegrants, binders, lubricants, etc. [0133]-[0135], wherein the excipients includes, for example, paraffins, vegetable oils, sugars, methylcellulose, starch, magnesium stearate, stearic acid and sodium lauryl sulphate. [0141], [0142]. One of ordinary skill in the art would have been motivated to use the crystalline form of Rudolph, Barth and Morissette (established above) in preparing the pharmaceutical composition or dosage form of Rudolph. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Rudolph teaches that dosage form of MDM2 inhibitors in table 1, i.e., 28 is prepared by solid form of MDM2 inhibitor, i.e., 28 [0144]; Rudolph teaches that the MDM2 inhibitor i.e., 28 is use in all its solid, preferably crystalline, forms [0083]; and Barth teaches that crystalline forms of compounds are ordinarily preferable to the non-crystalline forms in preparing acceptable dosage forms such as tablets or capsules because the crystalline forms have superior stability, advantageous in manufacturing procedures, and handling characteristics when compared to their amorphous counterparts.
Therefore, one of ordinary skill in the art would have been motivated to prepare Rudolph’s composition, i.e., tablet with pharmaceutically acceptable excipients including diluents, binders, and surfactant (sodium lauryl sulfate) using the crystalline form of MDM2 inhibitor, 28 taught by the combination of Rudolph, Morissette and Barth, and therefore, meet each and every limitation of claims 18-19, 21-22 and 25-28.
With regard to claims 23 and 24, Rudolph teaches that the dosage for oral use for MDM2 inhibitors, in particular for MDM2 inhibitors in table 1 (e.g., comp. 28), is from 1 mg to 2000 mg per dose, in a more preferred embodiment from 10 mg to 500 mg per dose; most preferred is from 10 mg to 100 mg per dose). All amounts given refer to the free base of the MDM2 inhibitor. [0144]. As described by MPEP 2144.05, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
§ 103 Rejection over Rudolph, Barth and Morissette in view Handbook of Pharmaceutical Excipients
Claim 20 is rejected under 35 U.S.C. 103 as being obvious over D. Rudolph et al. (US PG PUB 2020/0101079A1, 04/02/2020, “Rudolph” cited in the PTO-892 dated 05/29/2026) in view of W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 05/29/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 05/29/2026) as applied above to claims 1-9, 18-19, 21-25-28, further in view of R. Rowe et al. (Handbook of Pharmaceutical Excipients, Retrieved from Internet archive: https://www.gmpua.com/RD/RD/HandbookPharmaceutical%20Excipients.pdf, 5th edition 2006, pages 687-689, cited in the PTO-892 dated 05/29/2026).
The combination of Rudolph, Morissette and Barth teaches a pharmaceutical composition of the crystalline form of MDM2 inhibitor comp. 28 (Compound A) and pharmaceutically acceptable excipients including diluents, binders, and surfactants (sodium lauryl sulfate). However, the combination of Rudolph, Morissette and Barth does not teach that the amount of sodium lauryl sulfate is 0.1-5%.
The Handbook of Pharmaceutical Excipient teaches that sodium lauryl sulfate (sodium lauryl sulfate is the other name for dodecyl sodium sulfate, see the Handbook of Pharmaceutical Excipient, page 687, col. 1, Synonyms), is an anionic surfactant employed in a wide range of pharmaceutical formulations. It is a detergent and wetting agent effective in both alkaline and acidic conditions. [page 687, col. 1, last para.]. The Handbook of Pharmaceutical Excipient teaches that sodium lauryl sulfate use in an amount of 0.5-2.5% as an anionic surfactant. [Table I, page 687].
Therefore, one of ordinary skill in the art would have been motivated with reasonable expectation of success to use sodium lauryl sulfate taught by Rudolph in an amount of 0.1-5% in preparing a pharmaceutical composition of the crystalline form of compound A because the combination of Rudolph, Morissette and Barth teaches a pharmaceutical composition of the crystalline form of MDM2 inhibitor Compound A and sodium lauryl sulfate, and the Handbook of pharmaceutical Excipient teaches that is sodium lauryl sulfate employed in a wide range of pharmaceutical formulations as an effective anionic surfactant in both alkaline and acidic conditions in an amount of 0.5-2.5%. One of ordinary skill in the art would have been motivated to use sodium lauryl sulfate (sodium dodecyl sulfate) at 0.1-0.5% because the Handbook of pharmaceutical Excipients teaches that sodium lauryl sulfate uses as an anionic surfactant in an amount of 0.5-2.5%. Moreover, MPEP 2144.05 explains that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Furthermore, “Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” Therefore, the combination of Rudolph, Morissette, Barth and the Handbook of pharmaceutical Excipients teach each and every limitation of claim 20.
Response to Arguments
Applicant argues:
The generic teaching by Barth of the preference in using crystalline forms of active compounds is not a teaching or suggestion of the specific crystalline form of compound A as recited in at least claim 1. Morissette describes automated high-throughput crystallization to form polymorphs, salts, co-crystals and solvate forms of pharmaceutical compounds. At best, Morissette might suggest ways in which crystalline forms of MDM2 inhibitor compound 28 taught by Rudolph might be obtained. This is not a teaching or even a remote suggestion for providing the specific crystalline form of compound A as recited in claim 1. At best, the combinations of references teach: (1) that the use of compound A is known for treating cancerous tumors; and (2) that, generally speaking, crystalline forms of a pharmaceutical compound are preferable over non-crystalline forms as well as methods that can be used to crystallize pharmaceutical compounds. Applicant submits that this is an unreasonable assertion that clearly involves improper hindsight and reliance upon the claimed invention. There is no teaching or suggestion by Rudolph of a crystalline form of compound A, let alone the specific crystalline form as recited in claim 1.
Examiner response:
Applicants’ arguments have been fully considered but they are not persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Compound 28, taught by Rudolph, is an inhibitor of MDM2, known for treating cancer, i.e., active pharmaceutical agent. Rudolph teaches a short list of 36 MDM2 inhibitor and specifically teaches that “the MDM2 inhibitor is compound 28 [0114]. Rudolph teaches that the MDM2 inhibitor, compound 28, includes pharmaceutically acceptable salts and all its solid forms, preferably crystalline forms and in all the crystalline forms of its pharmaceutically acceptable salts, hydrates and solvates [0083]. Thus, the ability of compound 28 to form crystalline form is known to skilled artisans have access to Rudolph. Utilizing the routine “High-throughput salt selection” taught by Morissette [page 285-287] one of ordinary skill in the art would arrive at the claimed invention. Specifically, because Rudolph teaches that crystalline forms of the MDM2 inhibitors, i.e., compound 28 are preferred, and Barth also teaches that crystalline forms are preferred over non-crystalline forms; have superior stability; are preferred in formulation of dosage forms; and are advantageous in manufacturing procedures. Thus, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed crystalline form. One of ordinary skill in the art would have a reasonable expectation of success in following the teaching of Rudolph and utilizing the well-known and routine automated high-throughput screening described by Morissette arrive at the claimed invention because such acts are conventional and routine in the art. One ordinary skill in the art would be expected to apply methods within their technical grasp (such as automated high-throughput screening) to improve that which is already known in the art. Please note that argument against Cornillie are moot because Cornillie reference is removed from the prior art reference as discussed above on page 7.
Conclusion
Claims are 1-9 and 17-28 rejected. No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
