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 01/13/2022 claims priority from IN201921028370 filed on 07/15/2019, and PCT/IB2020/056641 filed on 07/15/2020.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/03/2025 has been entered.
DETAILED ACTION
The Applicant’s arguments submitted on 01/21/2026, have been received and have been carefully considered.
Claims 1, 4, 8, 10, and 22-23 were amended; claims 11, 14-21 were cancelled; claims 2-3, 5-7 and 12-13 were previously cancelled; and claim 24 was added. Claims 1, 4, 8-10, and 22-24 are pending.
Withdrawn Claim Objections
Objection to claim 17 for reciting “a patients”, is withdrawn in view of Applicant amendment file on 01/21/2026 that cancelled claim 17.
Withdrawn claim Rejections - 35 U.S.C. 112(b)
Rejection of claims 1, 4, 8-11, 14-16, and 21-23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for antecedent basis, is withdrawn in view of Applicant’s amendment filed on 01/21/2026 that amended claim 1 by removing the term “powder formulation”.
Rejection of claim 4 for antecedent basis is withdrawn in view of Applicant’s amendment filed on 01/21/2026 that remove the antecedent basis by reciting “… in a patient …”.
Rejection of claim 9 for antecedent basis is withdrawn in view of Applicant’s amendment filed on 01/21/2026 that remove the antecedent basis by reciting “…wherein the said pharmaceutical composition is reconstitutable with a diluent just before administration to a patient …”.
Rejection of claim 23 for reciting “preferably” is withdrawn in view of Applicant’s amendment filed on 01/21/2026 that deleted “preferably comprising less than …”.
Withdrawn Claim Rejections - 35 USC § 103
Rejection of claims 1, 4, 8-11, 14-16, and 21-23 under 35 U.S.C. 103 as being unpatentable over M. Pisak (US PG-PUB 2015/0125534 A1, 05/07/2015) in view of P. Shivakumar et al (WO 2015/004556 A1, 01/15/2015) and Handbook of Pharmaceutical Excipients, 5th edition, 2006 (pages 369-371, 472-475, 765-766, 821)), is withdrawn in view of the Applicant amendment submitted on 01/21/2026, that amended claim 1 by reciting forest berry as flavoring agent in an amount of 0.01-1%.
Rejection of claims 17-20 under 35 U.S.C. 103 as being unpatentable over M. Pisak (US PG-PUB 2015/0125534 A1, 05/07/2015) in view of P. Shivakumar et al (WO 2015/004556 A1, 01/15/2015,), further in view of R. Bhargava (US PG-PUB 2017/0312177A1, 11/02/2017), is withdrawn in view of the Applicant amendment filed on 01/21/2026 that cancelled claims 17-20.
Rejection of claims 1, 4, 8-11, 14-16, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over P. Purohit et al. (WO 2019/016673 A2, 01/14/2019), is withdrawn in view of the Applicant amendment submitted on 01/21/2026, that amended claim 1 by reciting forest berry as flavoring agent in an amount of 0.01-1%.
Rejection of claims 17-20 under 35 U.S.C. 103 as being unpatentable over P. Purohit et al. (WO 2019/016673 A2, 01/14/2019) in view of R. Bhargava (US PG-PUB 2017/0312177A1, 11/02/2017), is withdrawn in view of the Applicant amendment filed on 01/21/2026 that cancelled claims 17-20.
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 for “diluent”
Claims 8-9, 17, 19 and 21-22 recite that the composition comprises diluent.
Instant specification describes diluent as:
“The diluent can be selected from the group comprising of but not limited purified water, fruit juice, or syrup mixture thereof. The diluent can be used to reconstitute the powder form.” [Pg. 11, ln. 26-27].
As such, diluent is given the broadest reasonable interpretation as known in the art including water, juice, syrup, etc., or a mixture thereof, and it’s not limited to the recited examples.
Claim interpretation for “substantially free”
Claim 3 recites “the pharmaceutical composition according to claim 1, wherein the said composition is substantially free from any surfactant/stabilizer.”
The specification defines the term “substantially free” as:
The term "substantially free of surfactant / stabilizer" means the said pharmaceutical composition comprises less than about 1%, more preferably less than about 0.5%, most preferably less than about 0. 1% of surfactant/stabilizer by total weight of the20 composition. [Pg. 9, ln. 17-20].
As such, the term substantially free” will be interpreted consistent with the specification.
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 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.
Claims 1, 4, 8-10, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over M. Pisak (US PG-PUB 2015/0125534 A1, 05/07/2015, “Pisak” provided in the IDS dated 01/13/2022) in view of P. Shivakumar et al (WO 2015/004556 A1, 01/15/2015, “Shivakumar” provided in the IDS dated 01/13/2022), Handbook of Pharmaceutical Excipients, 5th edition, 2006 (pages 369-371, 472-475, 765-766, 821), gmpua.com/RD/RD/HandbookPharmaceutical%20Excipients.pdf, cited in the PTO-892 dated 10/21/2025), and P.J Sánchez-Segarra, et al. Food Chemistry, Volume 70, Issue 1, 2000, Pages 85-89, “Sánchez-Segarra” cited in the PTO-892).
Pisak discloses a powder formulation of imatinib in solid form reconstituted with a diluent just before use. [Pg. 2, [0025]]. Pisak discloses that the formulation comprise at least one pharmaceutically acceptable excipient selected from the group comprising filler, binder, preservative, sweetener, flavoring agent, and coloring agent, wherein the filler is selected from a group including mannitol, binder include cellulose derivatives e.g., Hypromellose phthalate. [[0032], [0033] and Example 1, [0062]]. Pisak teaches that sweetener is selected from the group comprising fructose, glucose, sucralose, lactose, maltitol, and the like, flavoring agent may be selected from the group comprising natural flavoring oils, vanilla, strawberry, and the like. [0043]-[0044]. Pisak discloses a powder formulation in Example 1 which comprises imatinib and excipients, including filler (e.g., microcrystalline cellulose) and binder (e.g., povidone). [Pg. 4, [0062]]. Pisak discloses that the powder composition is added to water, juice, or syrup as diluent. [Pg. 3, [0057]]. Pisak discloses examples of the imatinib powder formulation i.e., Example 1, wherein the formulation does not include surfactants or stabilizers. [Pg. 4, Example 1, [0062]]. Pisak discloses that the imatinib composition is administered orally. [0030]. Pisak’s Examples (1-4) include strawberry as flavoring agent in an amount of 0.4% of the composition.
Pisak does not teach wherein the imatinib is present in an amount of 80% to 95% by weight based on the total weight of the composition, the amount of mannitol of 10-15% w/w, the amount of hydroxypropyl methylcellulose is about 0.5-3% w/w, and the amount of sucralose is about 0.07-2% w/w. Pisak does not teach that the flavoring agent is forest berry.
However, in the same field of formulating powder imatinib compositions, Shivakumar teaches a granulate composition comprising 90-99.95 % w/w of imatinib mesylate, binder and disintegrant. [Pg. 4, 2nd para.]. Shivakumar teaches that the composition is up-scalable, and stable and suitable for treating cancer. [Pg. 4, last para.]. Shivakumar teaches that many possible imatinib formulations have been reported including imatinib granules with an amount of about 80% or more, and that imatinib granulating formulations provide higher stability. [Pg. 2-3]. Shivakumar teaches that in one of the preferred embodiments, it provides a solid oral pharmaceutical composition of imatinib mesylate comprising Imatinib mesylate: 96-99% w/w [Pg. 10, 3rd para.]. Shivakumar teaches that the binder is selected for a group that includes Hypromellose. [Pg. 15, 2nd para.]. Shivakumar teaches the preparation process of the imatinib formulation which comprises blending imatinib with a filler, dissolving the binder excipient in a solvent, and mixing imatinib mixture with the binder and solvent mixture, then drying the produced mixture, following by sieving to obtain the imatinib granules (powder). [Pg. 6, 1st para.].
The Handbook of pharmaceutical excipients provide recommendation on the excipient used in pharmaceutical preparation. The Handbook teaches that Hypromellose (hydroxypropyl methyl cellulose), is widely used in oral pharmaceutical formulation primarily used as a tablet binder, wherein concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-granulation processes. [Pg. 346, col. 1]. Handbook teaches that Hypromellose is widely used as an excipient in oral pharmaceutical formulations because Hypromellose is generally regarded as a nontoxic and nonirritant material, and can be taken daily since the levels consumed were not considered to represent a hazard to health. [Pg. 348, col. 2 2nd para.].
The Handbook of Pharmaceutical Excipients teaches that mannitol is widely used in pharmaceutical formulations as a diluent (10–90% w/w) in tablet formulations, where it is of particular value since it is not hygroscopic; with moisture-sensitive active ingredients; in direct-compression tablet applications; in wet granulations. The Handbook teaches granulations containing mannitol have the advantage of being dried easily, mannitol is commonly used as an excipient in the manufacture of tablet formulations because of its negative heat of solution, sweetness, and mouth feel. [Pg. 449, col. 1, last para.]. The Handbook teaches that mannitol is a naturally occurring sugar alcohol found in animals and plants; it is present in small quantities in almost all vegetables. [Pg. 452, col. 1, 1st para.].
The Handbook of Pharmaceutical Excipients teaches that sucralose is used as a sweetening agent in pharmaceutical applications. It has a sweetening power approximately 300–1000 times that of sucrose and has no aftertaste. It has no nutritional value, is noncariogenic, and produces no glycemic response. The Handbook teaches that the concentration of sucralose 0.03-0.24% [Pg. 742, col. 1]. The Handbook teaches that sucralose is generally regarded as a nontoxic and nonirritant material and is approved. [Pg. 743, col. 1, 1st para.].
Sánchez-Segarra teaches using wild berry (forest berry) as flavoring provides nutritional benefit. [Abstract, page 87, Table 2]. Sánchez-Segarra teaches that out of different flavors tested, wild berry flavor provides higher levels of iron [page 87, col. 1], and increases the manganese content.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to formulate Pisak’s imatinib powder formulation with more than 80% to 90% wt./wt. imatinib and with about 10-15% w/w mannitol, about 0.5-3% w/w hypromellose, a about 0.07-2% w/w sucralose and about 0.01-1%w/w forest berry as flavoring agent in view of the teachings of Shivakumar, the Handbook pharmaceutical excipients and Sánchez-Segarra.
One of ordinary skill in the art would have been motivated to formulate Pisak’s imatinib formulation with more than 80% to 90% wt./wt. imatinib and pharmaceutically acceptable excipients i.e., filler, binder, sweetener and flavoring agent with reasonable expectation of success because Pisak teaches high stable imatinib powder formulation with filler, binder, sweetener and flavoring agent and about 21% imatinib, and Shivakumar teaches imatinib granules (powder) formulation with excipients (filler and binder) with also high stability and more than 80% imatinib, which would motivate one of ordinary skill to increase Pisak’s imatinib amount to more than 80%. Moreover, Shivakumar teaches many imatinib granulating formulas with more than 80% imatinib and teaches that the granulating formulation provides more stability, which enable for scalable imatinib formulation for treating cancer. Furthermore, MPEP 2144.05.II.A explains: “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).”
One of ordinary skill in the art would have been motivated to specifically select mannitol (10-15% w/w), Hypromellose (0.5-3% w/w), and sucralose (0.07-2% w/w) as filler, binder and sweetener respectively from Pisak’s and Shivakumar list of excipient to formulate Pisak’s imatinib formulation with reasonable expectation of success because the Handbook of pharmaceutical excipients teaches that Hypromellose (hydroxypropyl methyl cellulose) is widely used as binder in oral pharmaceutical formulation at a concentration between 2% and 5% w/w, it’s the known binder in granulation processes, its safe, tolerable and can be taken daily; Mannitol is widely used in pharmaceutical formulations as a diluent (10–90% w/w) because its sweetness and mouth feel, it’s not hygroscopic, it’s the excipient for moisture-sensitive active ingredients and that granulations containing mannitol have the advantage of being dried easily; and Sucralose is selected as the sweetening agent in pharmaceutical applications at a concentration of 0.03-0.24% because it has no aftertaste, is noncariogenic, produces no glycemic response, nontoxic and nonirritant. The amount taught by the Handbook of pharmaceutical excipients encompasses and overlaps with the claimed amount of mannitol, Hypromellose, and sucralose, and 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). MPEP § 2144.05. 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).”
One of ordinary skill in the art would have been motivated to substitute the Pisak’s flavoring agent, strawberry with forest berry because Sánchez-Segarra teaches the benefit of selecting forest berry as flavoring over strawberry and other flavoring tested by Sánchez-Segarra. Sánchez-Segarra teaches that forest berry provides nutritional benefit such as increasing level of iron and manganese.
Therefore, the combination of Pisak, Shivakumar, the Handbook of Pharmaceutical Excipients and Sánchez-Segarra meet the limitations of claim 1.
Claim 22 is met because Pisak discloses that the powder composition is added to water, juice, or syrup as diluent [Pg. 3, [0057]] to form an imatinib composition that is administered orally. [0030].
Claim 23 is met because Pisak discloses examples of the imatinib powder formulation i.e., Example 1, wherein the formulation does not include surfactants or stabilizers. [Pg. 4, Example 1, [0062]].
Claim 4 Pisak discloses that the pharmaceutical formulations are for the treatment of certain types of cancer. Pisak discloses that imatinib is used for adult patients. [Pg. 1, [0005]]. Note that this limitation is given little patentable weight because Applicant is claiming a product and not a method of use. As a result, the recitation of the intended use in a patient that is an adult or pediatric patient does not modify the structure of the claimed product. See MPEP § 2111.
Claim 9 is met for the following reasons. The claim is drawn to the reconstitution time of the claimed imatinib powder formulation, wherein the reconstitution time required to dissolve the pharmaceutical composition in a diluent is less than 5 minutes. It is recognized that the prior art of Pisak Shivakumar, the Handbook of Pharmaceutical Excipients and Sánchez-Segarra teach substantially identical components of the claimed composition. As such, it is reasonable to assume that the prior arts composition will also reconstitute in less than 5 minutes. Applicants are reminded that the office does not have the facilities and resources to determine the reconstitution time of the imatinib powder formulation. In the absence of evidence to the contrary, the burden is on applicants to show that this property is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
With regard to the preparation of the powder imatinib composition of claim 8, Pisak discloses a preparation process of the formulations comprising the steps of: a) dissolving a certain amount of a binder in purified water; b) sieving imatinib mesylate, microcrystalline cellulose (i.e., filler) and remaining part of the binder with vibrating sieve; mixing them; and loading the mixture into the fluid bed granulator with vacuum; c) wet granulation by spraying the povidone solution obtained in step a) into the mixture obtained in step b); d) drying the granules obtained in step c) in dry granulator; e) coating the dried granules with Hypromellose phthalate, castor oil, water, ethanol and acetone in fluid bed granulator. f) sieving enteric coated imatinib mesylate granules and other excipients with fine granule with vibrating sieve; and mixing them; g) filling the final mixture into the bottles. [Pg. 3, [0047]-[0056]].
Pisak discloses the claimed steps of a) Blending imatinib with filler, b) Preparing the granulating fluid by mixing the excipients with solvent (ethanol and acetone). c) Granulating the dry mix material using the granulating fluid. d) Drying the granulated mass, in an order different than the claimed order. However, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) and Selection of any order of mixing ingredients is prima facie obvious. In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). See MPEP 2144.04 IV C. Selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) and Selection of any order of mixing ingredients is prima facie obvious. In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). See MPEP 2144.04 IV C. Therefore, claim 8 is obvious over Pisak.
Claim 24 is obvious over the combination of Pisak, Shivakumar, the Handbook of pharmaceutical excipients and Sánchez-Segarra for the following reasons. Pisak teaches that the imatinib salts are unstable and, the imatinib powder formulation display good stability to imatinib, [Pg. 2, [0027], [0029]]. Pisak teaches that based on the studies, the imatinib powder formulation display good stability to imatinib granules. [Pg. 3, [0046]], and have not met any stability problems during long term stability studies performed at 25±2° C. and 60±5% RH across a 0-, 3- and 6-month follow-up period; and accelerated stability studies performed at 40±2° C. and 75±5% RH across a 0-, 3- and 6-month follow-up period. [Pg. 3, [0059]]. It is recognized that the prior art of Shivakumar, the Handbook of pharmaceutical excipients and Sánchez-Segarra discloses substantially identical components of the claimed composition, and teaches that formulations display good stability to imatinib granules, and have not met any stability problems during long term stability studies performed at 25°C, 60% RH, 40°C and 75% RH across a 0-, 3- and 6-month follow-up period. As such, it is reasonable to assume that the prior art’s composition will also not have more than 3% w/w of total impurity of imatinib and assay of imatinib is in range of 90-110 % after being stored at 400C / 75 % RH for at least 3 months. However, Pisak is silent with respect to the degree of stability and the amount of impurity of imatinib. Applicants are reminded that the office does not have the facilities and resources to determine the stability of the imatinib powder formulation. In the absence of evidence to the contrary, the burden is on applicants to show that this property is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Response to Arguments
Note: the previous § 103 rejection is withdrawn, see above; however, the current 103 rejections are based on the combination of the same Pisak, Shivakumar and the Handbook of pharmaceutical excipients references. The arguments are addressed below.
Applicant argues:
Paragraph [0029] of Pisak discloses a pharmaceutical composition including imatinib mesylate in the α crystal form. Paragraph [0029] discloses that "Form a is described to be hygroscopic, there was a need to enable the stability by preventing imatinib mesylate of the pharmaceutical formulations of the invention in the α crystal form from absorbing moisture. Formulating the pharmaceutical formulations of the invention in powder form comprising enteric coated imatinib granules has prevented imatinib mesylate in the α crystal form from absorbing moisture. As a result, pharmaceutical powder formulations of the invention comprising enteric coated imatinib granules display good solubility and stability." Pisak therefore uses form a and specifically utilizes the enteric coating to prevent the imatinib from absorbing moisture. Shivakumar discloses that form a is hygroscopic and needle shaped. Shivakumar includes form SA of imatinib in their compositions. Form SA is non-needle shaped and not hygroscopic. A person skilled in the art would not have modified the composition of Pisak in view of the teachings of Shivakumar because a person skilled in the art would not have had a reasonable expectation of success. A person skilled in the art would not have expected that increasing the amount of form a imatinib mesylate used along with enteric coating to 80-90% based on the teachings of Shivakumar would result in a successful uncoated composition. Different forms of imatinib (e.g., a versus SA) have different crystalline forms and different thermophysical properties. The present disclosure does not involve enteric-coated granules. Instead, it provides a powder formulation that achieves stability through a fundamentally different approach without relying on enteric coating.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive for the following reasons. First, Pisak at [0029] describes that the composition provides stability to imatinib crystal form α specifically because of its hygroscopic nature, however, Pisak teaches that the crystal form shares same aqueous solubility and characteristics:
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Shivakumar, on the other hand, does not teach that the composition is not directed to crystalline form α. Shivakumar teaches that:
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as provided in 2145 (D. 1.), the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") (internal quotations omitted) (quoting DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009)); and Schwendimann v. Neenah, Inc., 82 F.4th 1371, 1381, 2023 USPQ2d 1173 (Fed. Cir. 2023) ("Although Oez [the prior art] used a white pigment with a cross-linking polymer, it does not discourage a skilled artisan from using the white pigment without a cross-linking polymer or lead the skilled artisan in a direction divergent from the path taken in the Appealed Patents. Thus, Oez's disclosure is substantial evidence that supports the Board's finding that Oez does not teach away from the proposed combination." In the instant case, Shivakumar teaches, page 5, 1st para.:
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Thus, Shivakumar teaches a composition which provides polymorphic stability to imatinib mesylate, which would provide motivation to utilize the amount of imatinib of Shivakumar of 90-99.5% of imatinib mesylate in Pisak’s composition. With respect to the fact the Shivakumar teaches that in an aspect the imatinib composition comprises film coated, patents are relevant as prior art for all they contain and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994),” see MPEP 2123. Shivakumar teaches a granulate composition comprising 90-99.95 % w/w of imatinib mesylate, binder and disintegrant. [Pg. 4, 2nd para.]. Shivakumar teaches that many possible imatinib formulations have been reported including imatinib granules with an amount of about 80% or more, and that imatinib granulating formulations provide higher stability. [Pg. 2-3], which would motivate one of ordinary skill in the art to formulate Pisak’s imatinib formulation (that include filler, binder, sweetener and flavoring agent) with more than 80% to 90% wt./wt. imatinib and pharmaceutically acceptable excipients i.e. filler, binder, sweetener and flavoring agent, and have reasonable expectation of success.
§ 103 Rejection over Purohit
Claims 1, 4, 8-11, 14-16, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over P. Purohit et al. (WO 2019/016673 A2, 01/14/2019, “Purohit” cited in the PTO-892 dated 10/21/2025) in view of P.J Sánchez-Segarra, et al. Food Chemistry, Volume 70, Issue 1, 2000, Pages 85-89, “Sánchez-Segarra” cited in the PTO-892).
Purohit teaches a stable dispersible pharmaceutical formulation comprising imatinib or a pharmaceutically acceptable salt thereof, and a one or more pharmaceutically acceptable excipients, wherein the formulation comprising an effective amount of imatinib or a pharmaceutically acceptable salt thereof, a flavoring agent, a sweetener and a one or more pharmaceutically acceptable excipients [Abstract].
Purohit teaches that the imatinib pharmaceutical formulation comprises diluents, binders, super-disintegrants, polymers, sweeteners, flavoring agents. [0042].
Purohit teaches that the binder can be cellulose derivatives, povidone, copovidone, etc. and the binder present in an amount from about 0.01% to 20% by weight of composition, preferably from about 3% to 15 % by weight of composition. [0045].
Purohit teaches that the concentration of imatinib in the composition is from 1% to 80% [0061].
Purohit teaches an exemplary composition including filler (mannitol), binder (crospovidone), sweetener (sucralose) and flavoring agent (cherry flavor):
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The above Purohit’s composition of Example 2 reads on claim 1 wherein the composition comprises imatinib, 35.5% filler (mannitol), 9% binder (crospovidone), 0.4% sweetener (sucralose) and 0.4% flavoring agent (cherry flavor). The composition of Example 2 differs from instant claim 1 composition in that the amount of imatinib is 50% (80-95% in the instant claim), and the amount of the binder is 9% in Purohit (0.5-3% in the instant claim). Also, Purohit does not teach that the flavoring agent is forest berry.
Sánchez-Segarra teaches using wild berry (forest berry) as flavoring provide nutritional benefit. [Abstract, page 87, Table 2]. Sánchez-Segarra teaches that out of different flavors tested, wild berry flavor provides higher level of iron [page 87, col. 1], and increases the manganese content.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to modify the above Purohit’s Example 2 composition by increasing the imatinib amount from 50% to between 80-95%, for example 80%, and decrease the amount of the binder from 9% to between 0.5-3%. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Purohit teaches that the amount of imatinib is between 1 to 80% and the amount of binder is preferably from about 3% to 15 % by weight of composition. As provided in 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).” 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).” Note that the instant specification does not provide definition to the relative term “about”, however, Purohit teaches that the term “about” “refers to any value which lies within the defined range by present inventors from a variation of up to ±10% of the claimed value. [0028].”
One of ordinary skill in the art would have been motivated to substitute the Purohit’s flavoring agent, cherry flavor with forest berry because Sánchez-Segarra teaches the benefit of selecting forest berry as flavoring agent over the other flavoring agents tested by Sánchez-Segarra. Sánchez-Segarra teaches that forest berry provides nutritional benefit such as increasing level of iron and manganese.
Therefore, the combination of Purohit and Sánchez-Segarra meet the limitations of claim 1.
Claim 22 is met because Purohit teaches that the invention is directed to a sachet formulation which is reconstituted with a diluent just before administering to a patient, wherein the diluent can be juice. [0041] Purohit also teaches that the composition is in the form of powder for reconstitution for oral administration. [0055].
Claim 23 is met because Purohit’s example 2 above, does not include surfactants or stabilizers. [Pg. 4, Example 1, [0062]].
With regard to claim 4, Purohit teaches that the patient is pediatric or adult [0009], for treating cancer. [0031].
Claim 9 is met for the following reasons. The claim is drawn to the reconstitution time of the claimed imatinib powder formulation, wherein the reconstitution time required to dissolve the pharmaceutical composition in a diluent is less than 5 minutes. It is recognized that the prior art of Purohit discloses substantially identical components of the claimed composition. As such, it is reasonable to assume that the prior arts composition will also reconstitute in less than 5 minutes. Applicants are reminded that the office does not have the facilities and resources to determine the reconstitution time of the imatinib powder formulation. In the absence of evidence to the contrary, the burden is on applicants to show that this property is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Claim 24 is drawn to the stability of the claimed imatinib powder formulation that does not have more than 3% or 1% of total impurity of imatinib. It is recognized that the prior art of Purohit discloses substantially identical components of the claimed composition, and teaches that formulations is a stable formulation and remain stable for a long period of time without compromising the therapeutic efficacy [0015], wherein the term “stable” means a drug substance and/or pharmaceutical composition for pharmaceutical use which remains stable as per ICH guidelines (“ICH guidelines” means composition remains stable for longer period of time at 25° C/60%+5% RH, 30° C/65%+5% RH, and 40° C/75%+5% RH conditions for a time period of at least 6 months) [0029]. As such, it is reasonable to assume that the prior art’s composition will also not have more than 3% w/w of total impurity of imatinib and assay of imatinib is in range of 90-110 % after being stored at 400C / 75 % RH for at least 3 months. However, Purohit is silent with respect to the degree of stability and the amount of impurity of imatinib. Applicants are reminded that the office does not have the facilities and resources to determine the stability of the imatinib powder formulation. In the absence of evidence to the contrary, the burden is on applicants to show that this property is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Instant claim 8 recites that the binder is hydroxypropyl methyl cellulose. One of ordinary skill in the art would have been motivated to substitute the binder crospovidone with hydroxypropyl methyl cellulose (Hypromellose) with reasonable expectation of success because Purohit teaches that the binder can be cellulose derivatives, povidone, copovidone, etc. [0045], Purohit teaches that the composition can be a solid dispersion of imatinib and a polymer wherein the polymer is Hypromellose, povidone, copovidone, etc. [0047], and Purohit teaches that the preferred excipients for reducing sedimentation rate and enhance homogeneity of the formula include hydroxypropyl methyl cellulose, most preferably present in an amount of about 5-50%. [0053]. Moreover, case law has established that it is prima facie obvious to substitute one known element for another to obtain predictable results. KSR Int'I Co. v. Teleflex, Inc., 550 U.S. 398 (2007).
Thus, with regard to claim 8, Purohit teaches that the pharmaceutical composition is prepared by a process comprising the steps of – preparing a blend of imatinib or a pharmaceutically acceptable salt thereof with fillers/diluents; mixing said blend with a one or more pharmaceutically acceptable excipients specifically super-disintegrants; subsequently lubricating the blend and at last either directly compressing the lubricated blend into tablets or filled into sachet dosage form [0062]-[[0066].
Response to Arguments
Applicant argues:
Purohit discloses mannitol as a diluent, hydroxymethyl cellulose as a film-forming agent, and does not disclose forest berry as a flavoring agent. Purohit does not disclose a powder composition of imatinib including mannitol as a filler, hydroxymethyl cellulose as a binder, sucralose as a sweetener, and forest berry as a flavoring agent. Additionally, the Office Action cites Examples 1 and 2 from Purohit. These examples relate to oral disintegrating tablets, wherein the imatinib content is 28.57% w/w in Example 1 and 50% w/w in Example 2, both of which are below the claimed range of 80% to 90% w/w.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive. First, with respect to the amendment of claim 1 that required forest perry as flavoring agent, the Purohit Rejection is modified and the claims are now rejected in view of Sánchez-Segarra, see the 103 Rejection above.
With respect to the Applicant argument that Purohit composition is a disintegrant tablet, Purohit teaches that the invention is directed to a sachet formulation which is reconstituted with a diluent just before administering to a patient [0041]. Purohit also teaches that the composition is in the form of powder for reconstitution for oral administration. [0055]. While Purohit teaches that the composition of Example 2 is for disintegrant table, Purohit teaches “the composition of the present invention may be in the form of tablets, dispersible tablets, granules, pellets, minitablets, sachets, chewable tablets, powder for solution, powder for reconstitution, orally disintegrating films, wafers, or a like thereof which can be easily disintegrate in oral cavity after administration or dispersed/reconstituted in a suitable medium during administration.”
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/M.M.A./
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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