DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Specification, Amendments to the Claims and Arguments/Remarks filed 15 December 2025, in response to the Restriction/Election Requirement Office Correspondence dated 15 September 2025, are acknowledged.
The listing of Claims filed 15 December 2025, have been examined. The election The applicant’s election of Group 2, 0.1 mg or 1 mg infigratinib oral minitablet inventions, without traverse is and the election of the species of microcrystalline cellulose as the excipient, sorbitol as the binder, and the cross-linked cellulose as the disintegrant are acknowledged. Claims 34, 36, 37, 38, 40, 42, 44, 45, 47, 49, 50-53, 55, 56, 62, 63, and 64-129 are pending. Claims 1, 2, 5, 6, 8-12, 14, and 24 are withdrawn from further consideration. Claims 34, 36-38, 40, 42, 44-47, 49-53, 55, 56, 62 and 63 are amended. Claims 3, 4, 7, 13, 15-23, 25-33, 35, 39, 41, 43, 46, 48, 54, and 57-61 are canceled and new claims 64-129 have been added.
Information Disclosure Statement
The Information Disclosure Statement (IDS), filed 10 March 2026, is acknowledged and has been considered.
Response to Amendment
The applicant’s remarks regarding the election of species and the reservation of rights are noted but do not alter the procedure of the application. The statement by the applicant that the elections are made without traverse and are for “initial search and examination purposes only” is noted, however, the restriction requirement is final and the election of species is binding for the purposes of this examination.
The applicant has elected, without traverse, specific species for excipients, binders, and disintegrants. Under the current pending claim set, as amended and filed 15 December 2025, independent claim 34 and its dependent claim 36 recite a minitablet that does not comprise a polyvinylpyrrolidone or a cross-linked polyvinylpyrrolidone. This is a negative limitation that excludes part of the non-elected disintegrant species. Claims 34 and 36 are examined because they are directed to compositions that generically include the elected species and exclude part of the non-elected disintegrants. However, the additional non-elected species in claim 36 (i.e., mannitol, magnesium stearate, and croscarmellose sodium) will not be examined, only the microcrystalline cellulose excipient of the currently amended claim 36 is under consideration.
Regarding pending independent claim 37 and its dependent claims 38, 40, 42, 44, 45, 47, 49-53 55, 56, and 62-67, as in claim 34, the limitation of a minitablet that does not comprise a polyvinylpyrrolidone or a cross-linked polyvinylpyrrolidone is claimed, and thus the claims are examined as generic claims (e.g., without further limitation to excipient, binder or disintegrant species), but are subject to the species election. The same applies to new independent claim 95 and its dependent claims 96-115 and new independent claim 127 and its dependent claims 128 and 129. The new claims added after the restriction requirement are subject to the binding species election made without traverse.
Regarding independent claim 68 and its dependent claims 69-82, the new claims recite non-elected excipients (mannitol) and non-elected disintegrants (a starch, a starch derivative, a clay, and a cross-linked cellulose derivative) are withdrawn from consideration under species restriction (election without traverse). The claims are examined but are subject to the species election made without traverse. Claim limitations that recite only microcrystalline cellulose and cross-linked cellulose or a subset thereof would be within the elected species. The non-elected excipients and disintegrants will not be examined and only microcrystalline cellulose, lactose or a combination thereof, and cross-linked cellulose are under consideration for claims 68-82. Similarly, the same applies to new independent claim 83 and its dependent claims 84-94, new independent claim 116 and its dependent claims 117-122, and new independent claim 123 and its dependent claims 124-126.
If any claim is found allowable that is generic to the elected and non-elected species (e.g., a claim reciting a disintegrant broadly enough to cover both the elected species and non-elected species), the examiner may withdraw the restriction requirement and rejoin the non-elected species claims for examination on the merits under MPEP 809.02(a). Any future pursuit of non-elected species will require a showing that the elected species is allowable and that the additional species are supported by the originally filed disclosure and comply with 35 U.S.C. 121.
Claim Objections
Claims 51, 53, 68, 83, 109, 117-119, 121, 123 and 125 are objected to because of the following informalities:
Claim 51 is objected to for the phrase “the minitablet weights about 7 mg”, wherein “weights” should be corrected to “weighs”.
Claim 53 is objected to for the phrase “wherein the minitablet is a made using (i) dray granulation…”. The "a made" is grammatically incorrect and should read "made" and "dray granulation" is a typographical error and should read "dry granulation". The grammatical errors render the claim unclear and should be corrected (e.g., "wherein the minitablet is made using (i) dry granulation, (ii) compression, or (iii) dry granulation and compression.").
Claims 68 and 83 are objected to for the grammatical error “consists” which should be “consist”. The subject "one or more disintegrants" is plural, but the verb "consists" is singular. This is a subject-verb agreement error and should read "consist essentially of".
Claim 109 appears to incorrectly be drafted to depend from claim 99 rather than claim 95. Appropriate correction is required if the dependency recited is a claim drafting typographical error.
Claims 117-119, and 121 refer to “The compressed solid dosage of claim 116”, however claim 116 recites “A compressed solid dosage form” and other claims depending from claim 116 (claims 120 and 122) refer to “the compressed solid dosage form of claim 116”. For consistency, claims 117-119 and 121 should add the word form after dosage. Similarly, claim 125, depending from claim 123, omits the word form after dosage. The use of the truncated term “dosage” without the word “form” creates confusion as to whether the claim refers to the same composition. The dependent claims should consistently recite "form" to maintain antecedent basis.
Claim 123 is also objected to for the phrase “about 5% to about 10% by weight a disintegrant”, which is missing the preposition “of” and should be corrected to “about 5% to about 10% by weight of a disintegrant”.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which Applicant regards as his invention.
Claims 37, 38, 40, 42, 44, 45, 47, 49-53, 55, 56, 62, 63, 67-94, and 116-129 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claims 37, 44, 50, 68, 69, 83, 116-119, 123 and 127 recite a component at a specified weight percentage, however, the claims fail to specify what the percentage weight is relative to, leading to ambiguity in the scope of the claims. The claims do not clarify whether the percentage weight of the component is relative to the total weight of the entire minitablet or solid dosage form including or excluding the intra-granular blend, the extra-granular blend, or a coating, another undefined reference. Without an explicit reference, the percent weight could be interpreted in multiple ways, rendering the claim scope unclear. Claims must be "definite" to inform the public of the invention's boundaries with reasonable certainty (Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014)) and provide clear meaning to a skilled artisan (MPEP 2173.02). To overcome this rejection, the applicant may mend the claims to specify the reference basis for the percent weight (e.g., about 5% by weight of the total solid dosage form including the intra-granular blend, the extra-granular blend, and any optional coating) or provide a definition in specification clarifying the basis for percent weight where not explicitly stated. Dependent claims 38, 40, 42, 45, 47, 49, 51-53, 55, 56, 62, 63, and 67, 70-82, 84-94, 120-122, 124-126, 128 and 129 are included in this rejection because they do not cure the defect noted above.
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.
This application currently names joint inventors. 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.
Claims 34, 36, 37, 38, 40, 42, 44, 45, 47, 49, 50-53, 55, 56, 62, 63, and 64-129 are rejected under 35 U.S.C. § 103 as being unpatentable over Legeai-Mallet (WO-2020065034-A1; published 02 April 2020, hereinafter referred to as “WO ’034”) in view of Legeai-Mallet (US-20150011560-A1; published 08 January 2015, hereinafter referred to as “US ’560”) and in further view of Zhang (Zhang et al., The Development of Minitablets for a Pediatric Dosage Form for a Combination Therapy. J Pharm Sci. 2020 Dec;109(12):3590-3597; Epub 2020 Sep 1), Omari (Omari, Formulation and in vitro/in vivo evaluation of esomeprazole enteric coated minitablets. J. Drug Del. Sci. Technol. 2017;39:156–165), and Quazi (Quazi et al., Design, Development and Optimization of Mini-Tablet Filled Capsule System of Terbutaline Sulphate for Controlled Drug Release. Research J. Pharm. and Tech. 6(12): Dec. 2013; Page 1350-1356).
US ’560 teaches the use of infigratinib (BGJ-398, compound 1h) for treating FGFR3-related skeletal diseases, including achondroplasia and hypochondroplasia (claims 1-3; ¶[0081]). US ’560 discloses that the compound can be formulated with pharmaceutically acceptable excipients (¶[0082]), administered orally (¶[0098]), and is particularly intended for pediatric patients (¶[0101]). US ’560 further teaches that the exact amount of antagonist varies according to the age and weight of the patient (¶[0099]), recognizing the need for dose flexibility.
WO ’034 teaches infigratinib as an FGFR inhibitor for treating FGFR3-related disorders such as achondroplasia (page 1, lines 33-34; page 5, lines 5-8). D1 discloses that infigratinib can be formulated as a salt (e.g., infigratinib monophosphate) in oral solid dosage forms including tablets, capsules, and granules (page 6, lines 8-13), using standard excipients and techniques (page 5, lines 30–31). WO ’034 also teaches broad dosage ranges, including low-dose administration of 0.1-2.5 mg (page 5, lines 21-24), encompassing the instant claimed doses of 0.12 mg and 1.2 mg.
Zhang teaches that minitablets are particularly suitable for pediatric applications due to their ability to enable flexible dose adjustment via administration of multiple units (page 1, Abstract). Zhang defines minitablets as compressed tablets with diameter less than 2.5 mm (page 1, Introduction). Zhang explicitly teaches a manufacturing process comprising dry blending, dry granulation (roller compaction) followed by compression into minitablets using a multi-punch tablet press with 2 mm tooling, producing minitablets weighing 6.5 mg (page 2, Minitablets Manufacturing). The minitablets were formulated with mannitol, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate (page 2, Materials). The active compounds were used at 20-30 wt%, leaving 70–80% excipients. Zhang also teaches film coating of minitablets at 0-25% weight gain.
Omari teaches 2.5 mm minitablet formulations containing 5.6-7.5% disintegrant (crospovidone, talc) and 0.5% magnesium stearate lubricant (page 2, Table 1). The minitablets weighed approximately 10.5-10.7 mg and contained 1.6-1.8 mg of active ingredient per minitablet, corresponding to 15.3-16.9% active ingredient, 73.7-74.2% filler (Avicel® microcrystalline cellulose and lactose (page 2, Table 1).
Quazi teaches 6 mm, 50 mg minitablet formulations containing 1.5-4% active ingredient (terbutaline sulphate), 88.5-93.6% total filler (including mannitol, hydroxypropyl cellulose, and anhydrous dibasic calcium phosphate), 0-7.2% disintegrant (sodium starch glycolate and croscarmellose sodium), and 1.2% magnesium stearate lubricant (page 7, Table 1). The minitablets were filled into capsules.
One of ordinary skill in the art, seeking to formulate low-dose oral solid dosage form of infigratinib for pediatric use as taught by US ’560 and WO ’034, would have been motivated to look to Zhang, which teaches that minitablets of approximately 2 mm dimension and 6.5-8 mg weight are suitable for pediatric administration. The skill would further consult Omari and Quazi for conventional excipient ranges. It was well-known in the art to create small tablets or minitablets for pediatric or geriatric populations, and to formulate such tablets with standard excipients like mannitol, microcrystalline cellulose, magnesium stearate, and croscarmellose sodium. One of skill in the art of pharmaceutical formulations would be familiar with formulating poorly soluble drugs using fillers like microcrystalline cellulose and mannitol and optimizing them within specific percentage ranges to achieve desired tablet properties. Further, one of skill in the art would also be familiar with the use of formulation disintegrants such as croscarmellose sodium and starches at specific concentrations (e.g., 5-10%) to control disintegration time. Therefore, it would have been obvious to one of ordinary skill in the art prior to the instant effective filing date, seeking to formulate a stable and bioavailable oral dosage form of infigratinib, to look to the conventional formulation principles to optimize excipients for the formulation to arrive at the recited percentages of filler and disintegrant.
The motivations to scale down from larger minitablets of Quazi’s 6 mm, 50 mg tablets to smaller 2 mm, 7-11 mg minitablets include improving pediatric swallowability (Zhang (Abstract) and evidentiary reference Mitsui et al., Swallowability of Minitablets among Children Aged 6-23 Months: An Exploratory, Randomized Crossover Study. Pharmaceutics. 2022 Jan 15;14(1):198)), enabling precise mg/kg dosing for low therapeutic doses consistent with that of what is taught for infigratinib for pediatric use as taught by US ’560 (¶[0099]) and WO ’034 (page 5, lines 21-24), avoiding tablet splitting, increasing manufacturing throughput via multi-tip tooling as evidence by Zhang (page 2, Minitablets Manufacturing). The selection of a specific size (e.g., 2.0-2.2 mm) and weight (e.g., 7-11 mg) for a minitablet is a mater of routine optimization for a person of ordinary skill in the art, wherein these dimensions and weights are conventional for minitablets used in pediatric formulations. There is no evidence that the specific dimensions or weight ranges provide any unexpected or synergistic effect.
Thus, infigratinib monophosphate active ingredient is taught by US ’560 (¶[0081]) and WO ’034 (page 6, lines 8-13); 0.12 mg or 1.2 mg dose are taught by WO ’034 (page 5, lines 21-24; 0.1-2.5 mg range); minitablets of 2.0-2.2 mm dimension are taught by Zhang (2 mm diameter, 2 mm height); minitablet weight of about 7-11 mg is taught by Zhang (6.5 mg uncoated; 6.5-8.125 mg coated) and Omari (10.5-10.7 mg); MCC, mannitol, and lactose fillers are taught by Zhang (MCC, mannitol) and Omari (MCC, lactose). Low active dose 85-95% filler is taught by Quazi (88.5-93.6%) and is a routine calculation for 0.12 mg dose in 7-11 mg tablet; High active dose filler of 70-80% is taught by the calculated excipient range used by Zhang and Omari (73.7-74.2%); disintegrant of starch, starch derivative, or cross-linked cellulose is taught by Quazi (sodium starch glycolate, croscarmellose sodium) and a disintegrant use range of 5-10% is taught by Omari (5.6-7.5%) and Quazi (7.2%); inclusion of a lubricant (magnesium stearate) from about 0.25-1% is taught by Omari (0.5%) and Quazi (1.2%). The absence of PVP and cross-linked PVP is taught by the omission of such in the formulations of Zhang without PVP/crospovidone and Omari and Quazi wherein omission is routine choice. The applicant has not provided any evidence that the absence of these known excipients provides a critical or unexpected technical effect. Rather, it is a mere choice of alternative from the myriad of known excipients, as evidence by the instant specification itself listing numerous other acceptable disintegrants, binders, and fillers including polyvinylpyrrolidone (PVP) and cross-linked polyvinylpyrrolidone (crospovidone) (¶[0030], ¶[0033], ¶[0034], ¶[0040], ¶[0042], ¶[0044], ¶[0089], ¶[0100], ¶[0103], ¶[0118]-[0120], and ¶[0138]-[0141])and it is used in two out of the four formulations in the specification examples Example 3.1, Table 1, ¶[0227] as crospovidone and povidone and Example 3.3, Table 3, ¶[0228] as crospovidone and povidone; absent in Example 3.2, Table 2, ¶[0228] and Example 3.4, Table 4, ¶[0229]), confirming that the claimed compositions are merely one of several conventional options. Therefore, it would have been obvious to one of ordinary skill in the art to formulate infigratinib into a minitablet of a routine size and weight using standard excipients, including the specific excipients recited in the claims, in view of the prior art teachings.
Dry granulation, blending, compression, or all is taught by Zhang’s blending, roller compaction followed by compression, wherein the solid dosage further comprises a capsule is taught by Quazi’s minitablets filled into capsules and Omari’s capsule containing minitablets. Zhang teaches formulation into granules as an intermediate before compression to a final solid dosage form and a 0-25% film coating. The use of a "granule" as a solid dosage form (e.g., filled into a capsule) is a conventional alternative to a compressed tablet. The recitation of a granule with a specific weight (7-11 mg) and dimension (2.0-2.2 mm) is a direct reflection of the properties of the final compressed minitablet or the granule itself, and such sizes are conventional. A "minitablet" is, by its nature, is a compressed solid dosage form. Claiming a "compressed minitablet" does not add a limitation that is not already inherent in the concept of a minitablet. The use of dry granulation, blending and/or compression to form such tablets is a conventional manufacturing technique and does not impart patentability.
The claimed percentage ranges are the direct result of routine formulation calculations, wherein a 0.12 mg dose in 7-11 mg tablet would be 1.1-1.7% active ingredient, falling within the claimed 1-9% and 1-10% ranges. A 1.2 mg dose in 7-11 mg tablet would be 10.9-17.1% active ingredient, falling within the claimed 10-20% range. Filler percentages reflect the balance after accounting for the active ingredient, disintegrant, and lubricant, and are taught by Quazi (88.5-93.6%), Omari (73.7-74.2%), and Zhang (70-80% excipients). The selection of the specific ranges (e.g., 1-9%, 1-10% or 85-95% filler) is a straightforward optimization of known formulation parameters to achieve a tablet of a desired size (2.0-2.2 mm) and weight (7-11 mg). Thus, the claimed percentages are not critical selections but rather routine design outcomes dictated by the target dose and tablet size.
In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003) teaches that optimization of result-effective variables is prima facie obvious where the prior art discloses a general range and the claimed range is a mere optimization achieved through routine experimentation. Here, WO ’034 discloses a broad dosage range (0.1-2.5 mg) encompassing the claimed doses, Zhang discloses minitablets with similar dimensions and excipients, Omari and Quazi disclose overlapping excipient percentages. The selection of specific values within these ranges is a matter of routine optimization. In addition, MPEP 2144.05 provides that when a prior art reference teaches a composition and a particular property or result is expected, the substitution of one known excipient for another to achieve a predictable result is obvious. The omission of PVP and crospovidone is such a substitution, as these excipients are optional and were omitted in Zhang, Omari, and Quazi formulations.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to formulate infigratinib monophosphate into the claimed minitablets by combining the active ingredient and pediatric indication teachings of US ’560 and WO ’034 with the minitablet format, dimensions, manufacturing processes of Zhang, and excipient percentage ranges and capsule formulation of Omari and Quazi. The claimed ranges represent routine optimization, and the omission of PVP and crospovidone is an obvious as it is omitted in some of the prior art formulations.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L. SCOTLAND whose telephone number is (571) 272-2979. The examiner can normally be reached M-F 9:00 am to 5:00 pm EST.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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