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 Claims and Arguments/Remarks filed 08 July 2026, in response to the Office Correspondence dated 08 April 2026, are acknowledged.
The listing of Claims filed 08 July 2026, have been examined. Claims 34, 36, 37, 38, 40, 42, 44, 45, 47, 49-51, 53, 55, 63-65, 67, and 130-188 are pending. Claims 1-33, 35, 39, 41, 43, 46, 48, 52, 54, 56-62, 66, and 68-129 are cancelled; claims 34, 36, 37, 38, 40, 42, 44, 45, 47, 49-51, 53, 55, 63-65, and 67 are amended and new claims 130-188 have been added. The newly added claims are supported by the originally-filed disclosure.
Information Disclosure Statement
The Information Disclosure Statement (IDS), filed 08 July 2026, is acknowledged and has been considered.
Response to Amendment
The entire prior claim set has been replaced with new claims, via amendment to the previous claims or newly introduced claims. While certain amendments clarify claim scope and overcome specific informalities and indefiniteness issues previously identified in the prior Office Correspondence, the amended claims continue to recite subject matter that would have been obvious to one of ordinary skill in the pharmaceutical formulation art at the time of the invention.
The corresponding objections or rejections directed solely to the cancelled claims are rendered moot.
The prior objections to claims 51 and 53 are withdrawn. Claim 51 now recites “weighs,” and claim 53 now recites “made using dry granulation.” The remaining previously objected claims were canceled. Accordingly, the objections are withdrawn.
Independent claim 37 now expressly defines percent w/w as the mass of a component per total mass of the minitablet multiplied by 100. Newly added independent claims 149 and 169 likewise expressly establish that the weight percentage is relative to the total mass of the compressed pharmaceutical composition. Accordingly, the rejection previously made under 35 U.S.C. §112(b) on the ground that the reference basis for the recited weight percentages was unclear is withdrawn.
Regarding the prior rejections under 35 U.S.C. §103, given that all previous claims have been amended or cancelled, and a significant number of new claims have been added, the claim set filed 08 July 2026 is an entirely newly presented claim set. As such, for simplicity and clarity of the record, the previous rejections of the claims under 35 U.S.C. § 103 are withdrawn and the rejections are newly restated for the amended claims and the new claims, as detailed below.
The amendments, however, do not affect the substantive scope of the claims relative to the cited prior art in the prior obviousness analysis. The amendment to claim 34 narrows the scope by adding weight and dimension limitations and the dependent claims 36-38, 40, 42, 45, 47, 50, 55, and 63 do not add notable distinctions to the previous limitations.
Claim 44 has been amended to recite about 1% w/w to about 9% w/w infigratinib monophosphate, a tablet weight of about 7 mg, and a tablet dimension of about 2 mm. These amendments merely define formulation parameters that would have resulted directly from selecting a 0.12 mg dose within a 7 mg tablet. Optimization of these values represents ordinary pharmaceutical formulation design and does not demonstrate criticality or unexpected results. The dependent claim 49 does not add notable distinctions to the previous limitations.
Claim 50 now additionally recites that the claimed minitablet has a dimension of approximately 2 mm. The amendment does not distinguish the claim from the cited prior art. The dependent claims 51, 53, 64, 65, and 67 do not add notable distinctions to the previous limitations.
The applicant has cancelled several previously pending independent claims and introduced new independent claims 139, 149, and 169 directed to additional dosage strengths and formulation percentages. The newly added independent claims incorporate substantially the same formulation concepts previously under examination while recasting the claims in alternative statutory classes or dosage formats. Merely reorganizing previously claimed formulation limitations into newly drafted independent claims does not, impart patentable distinction where the underlying formulation parameters remain taught or suggested by the cited prior art.
Primarily, the applicant has amended the independent claims to emphasize that the claimed dosage forms are compressed pharmaceutical compositions or compressed tablets. However, the cited prior art already teaches compressed tablet manufacture. Accordingly, the added "compressed" limitation merely recites the conventional manufacturing process already employed by the prior art reference Zhang and therefore does not distinguish the claimed invention.
In summary, the amendments overcome the previously identified informal claim objections; the amendments overcome the previously applied 35 U.S.C. §112(b) rejection directed to the ambiguity of the weight percentage basis; the amendments narrow the scope of the claims by reciting specific dosage amounts, tablet weights, dimensions, and manufacturing characteristics; however, the amendments do not overcome the outstanding rejection under 35 U.S.C. §103, because the additional limitations constitute routine optimization of known pharmaceutical formulation variables or expressly recite characteristics already taught by the cited prior art.
Additionally, the newly added claims 130-188 are considered under the same obviousness analysis, together with any additional issues arising, as detailed below. The newly added claims largely recite subject matter that was previously encompassed by the originally pending claims or constitutes obvious refinements of the previously examined subject matter. The newly added claims remain subject to examination under all applicable statutory requirements, including 35 U.S.C. § 101, 102, 103, 112, and any previously imposed restriction or election requirements.
Many of the newly added claims merely specify conventional pharmaceutical excipients that are routinely employed in compressed tablet formulations (e.g., fillers comprising microcrystalline cellulose, mannitol, lactose, combinations thereof, croscarmellose sodium, lubricants, and conventional quantitative ranges for each excipient). The newly drafted claims primarily rearrange previously recited formulation limitations into alternative claim formats while incorporating conventional excipient percentages and dosage strengths. The underlying inventive concept previously examined has therefore not materially changed. In addition, merely reciting the compressed formulation as part of a "solid dosage form" does not patentably distinguish the claimed subject matter.
Moreover, the applicant previously elected, without traverse, the inventions directed to Group II (0.1 mg/1 mg infigratinib oral minitablets) and the elected species comprising microcrystalline cellulose as the excipient, sorbitol as the binder, and cross-linked cellulose as the disintegrant. That election remains binding during examination of this application. Under MPEP § 821 and § 821.02, claims directed to nonelected species remain withdrawn from further consideration pursuant to 37 CFR 1.142(b). The applicant cannot circumvent a binding election of species by merely introducing new claims after election that specifically recite previously non-elected embodiments.
To the extent newly added claims expressly recite previously non-elected excipients, fillers, lubricants, or disintegrants (e.g., claims 131-133, 141-143, 153-155, 173-175, 138, 148, 165, and 185 requiring the previously identified nonelected mannitol and/or croscarmellose-sodium species), such subject matter remains outside the elected species and is not entitled to substantive examination on the merits in the present application. Accordingly, examination of these newly added species is limited to the elected species. To the extent claims encompass both elected and non-elected embodiments, examination is conducted only with respect to the elected species consistent with the previous Office Correspondence.
New Rejections
The following new rejections are made from the previous Office Correspondence dated 08 April 2026, as the Applicant's amendment necessitated the new grounds of rejection presented below based on the amended/newly cited limitations.
Claim Objections
Claims 162 and 182 are objected to because of the following informalities:
Claim 162 recites, “…and 0.25% w/w to about 1% w/w of the lubricant.” The lower limit is not preceded by “about”, making it an exact value while the upper limit is approximate. The applicant should amend the claim, if required, if the exact value is not intended.
Claim 182 recites, “and .25% w/w to about 1% w/w of the lubricant.” For consistency with conventional claim-drafting practice and the disclosure, the limitation should be amended to recite “about 0.25% w/w to about 1% w/w.” The specification expressly discloses lubricant ranges beginning at about 0.25% w/w.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. § 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 151, 166, 171, and 186 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
New or amended limitations lacking support in the original disclosure violate the written-description requirement (see MPEP § 2161 and § 2163). Claims 151, 166, 171, and 186 directed towards capsules containing a compressed pharmaceutical composition are rejected under 35 U.S.C. §112(a) for lack of adequate written description.
Independent claims 149 and 169 recite a, “solid dosage form comprising: a compressed pharmaceutical composition comprising …”. Claims 151 and 171 then require that the “solid [dosage] form” be a capsule, and claims 166 and 186 impose the same capsule limitation through claims 162 and 182, respectively. The originally-filed specification as filed does contain a general definition stating that a “solid dosage form” can include, among other things, tablets and capsules. That general definition, standing alone, however, does not describe the more specific combination now claimed: a capsule solid dosage form comprising the particular claimed compressed pharmaceutical composition.
The detailed pharmaceutical-composition disclosure specifically directs the infigratinib-monophosphate formulations to minitablets. For example, the specification states that the pharmaceutical composition may be a minitablet and then describes minitablets for oral delivery comprising infigratinib monophosphate and pharmaceutically acceptable excipients. The manufacturing examples likewise describe compression of a final blend directly into minitablets using 2-mm or 2.2-mm round tooling.
Examples 3.2 and 3.4 provide detailed compositions for such 7-mg compressed minitablets. Example 3.2 contains 0.1175 mg API, mannitol, MCC, 5% croscarmellose sodium, and magnesium stearate; Example 3.4 contains 1.1750 mg API, mannitol, MCC, 5% total croscarmellose sodium, and magnesium stearate. The specification therefore demonstrates possession of compressed minitablets/tablets. The disclosure does not, however, identify a capsule containing one or more of those compressed pharmaceutical compositions, does not describe filling compressed minitablets into a capsule, and does not provide an embodiment in which the claimed “solid dosage form” is a capsule comprising the recited compressed pharmaceutical composition.
The inclusion of “capsules” in a general definition listing multiple possible solid dosage forms does not, without more, reasonably convey possession of every later-claimed combination of the detailed minitablet formulation with each generic solid-dosage-form species. The claimed capsule/compressed-composition combination must itself be reasonably conveyed by the disclosure. Here, there is an absence of a disclosed capsule/compressed-minitablet combination in contrast to the detailed tablet-specific disclosure. Accordingly, claims 151, 166, 171, and 186 are rejected for lack of adequate written description.
The applicant may traverse the rejection by identifying where the application, as originally filed, reasonably conveys possession of a capsule comprising the claimed compressed pharmaceutical composition, rather than merely identifying the generic definition of “solid dosage form.”
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 157 and 177 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 157 and 177 improperly refer to a “compressed pharmaceutical composition” when the claims from which they depend are directed to a “solid dosage form.” Thus, the claims lack of antecedent basis and inconsistent nomenclature renders the scope of these claims unclear.
Claims 157 and 177 depend from a claim directed to a “solid dosage form” but recite “The compressed pharmaceutical composition of claim…,” creating a mismatch in the claimed category and a lack of antecedent basis. The claims should be redrafted to refer to the proper category (e.g., “The solid dosage form of claim 156… wherein the disintegrant is…”) if that is the intended scope.
Claim 177 contains the identical defect, it depends from claim 176, a solid dosage form, but recites “The compressed pharmaceutical composition of claim 176…”. Correction is required.
The categorical mismatch of both claims makes the scope of the dependent claims uncertain, thus, they are indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. § 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. § 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. § 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 157 and 177 are rejected under 35 U.S.C. § 112(d) or pre-AIA 35 U.S.C. § 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 157 and 177 are likewise rejected under 35 U.S.C. §112(d) as being in improper dependent form.
Claim 156 recites, “The solid dosage form of claim 149…” Claim 157, however, recites, “The compressed pharmaceutical composition of claim 156…” Claim 156 does not claim a “compressed pharmaceutical composition” as the claimed subject matter; it claims a solid dosage form dependent from claim 149. Claim 157 therefore changes the subject of the parent claim from the claimed solid dosage form to one component contained within that dosage form. A proper dependent claim must incorporate all limitations of its parent claim and further limit the same claimed subject matter (see MPEP §608.01(n)). Accordingly, claim 157 does not comply with §112(d). The rejection may be overcome, for example, by amending claim 157 to recite, “The solid dosage form of claim 156….”
Claim 177 is rejected under 35 U.S.C. §112(d) for substantially the same reason. Claim 176 recites, “The solid dosage form of claim 169…” Claim 177 instead recites, “The compressed pharmaceutical composition of claim 176…” Claim 177 therefore changes the claimed subject matter from the “solid dosage form” of claim 176 to the “compressed pharmaceutical composition,” rather than further limiting the solid dosage form while incorporating all limitations thereof. Claim 177 should be amended, for example, to recite, “The solid dosage form of claim 176, wherein the disintegrant is croscarmellose sodium.”
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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, 49-51, 53, 55, 63-65, 67, and 130-188, to the extent under examination on the merits, are rejected under 35 U.S.C. §103 as being unpatentable over Legeai-Mallet (WO2020065034A1; published 02 April 2020, hereinafter “WO ’034”), in view of Legeai-Mallet (US20150011560A1; published 08 January 2015, hereinafter “US ’560”), and in further view of Ribeiro et al. (US20170007602A1; published 12 January 2017, hereinafter “Ribeiro”), 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; hereinafter “Zhang”), Omari (Formulation and in vitro/in vivo evaluation of esomeprazole enteric coated minitablets. J. Drug Del. Sci. Technol. 2017;39:156-165), and 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; hereinafter “Quazi”).
Simply put, the pending claims recite, inter alia, approximately 0.12 mg and 1.2 mg infigratinib-monophosphate minitablets, approximately 7 mg and 11 mg minitablets, approximately 2.0-2.2 mm dimensions, specified drug/filler/disintegrant/lubricant proportions, selected filler and disintegrant species, capsule and tablet embodiments, and products made using dry granulation.
WO ’034 teaches infigratinib low-dose compositions, oral tablets, and salt forms
WO ’034 identifies infigratinib as NVP-BGJ398/BGJ398/BGJ-398 and teaches that the therapeutically effective dose depends upon, among other factors, the specific composition, age, body weight, route of administration, and other patient-specific considerations (p. 5, ll. 15-21). The reference expressly states that pharmaceutical compositions may contain 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0 mg, and higher amounts of active ingredient (p. 5, ll. 20-28). WO ’034 further teaches administration of infigratinib in a pharmaceutical composition combined with pharmaceutically acceptable excipients (p. 5, l. 29- p. 6, l. 3).
WO ’034 expressly identifies suitable oral unit dosage forms as including “tablets, gel capsules, powders, granules” and oral suspensions or solutions (p. 6, ll. 8-10). It further teaches that infigratinib can be formulated in neutral or salt form and identifies pharmaceutically acceptable acid-addition salts made with inorganic acids including phosphoric acid (p. 6, ll. 10-17).
Accordingly, WO ’034 expressly supplies the teachings of pharmaceutical compositions comprising infigratinib, including low amounts of 0.1 and 1.0 mg infigratinib, pharmaceutically acceptable excipients, oral dosage forms including a tablet and capsule, and neutral or salt form including salts formed with phosphoric acid.
WO ’034 does not, however, expressly identify the claimed specific infigratinib monophosphate species. That limitation is supplied, as described below by Ribeiro.
US ’560 teaches infigratinib (BGJ398) oral administration and pediatric treatment
US ’560 expressly identifies compound 1h as BGJ-398 (¶[0081]). US ’560 teaches that the antagonist is provided in a pharmaceutically acceptable carrier, excipient, or diluent (¶[0096]). It lists numerous conventional pharmaceutical excipients, including cellulose-based substances and polyvinylpyrrolidone (¶[0097]). US ’560 expressly teaches that “[t]he oral route can also be used,” provided that the composition is in a form suitable for oral administration (¶[0098]). US ’560 further teaches that the exact amount and composition vary according to factors including “the age and the weight of the patient,” disease, mode of administration, frequency, and other ingredients (¶[0099]).
Most significantly for the motivation to employ a pediatric dosage form, US ’560 states that the subject is preferably human and “more preferably a child,” and teaches administration during all or part of the child’s growth period (¶[0101]). Thus, US ’560 provides an expressed reason to adapt an oral BGJ398/infigratinib pharmaceutical composition to the requirements of a pediatric patient, including dose and formulation adjustment based upon age and weight.
Ribeiro teaches infigratinib monophosphate and quantitative excipients
Ribeiro is directed to pharmaceutical formulations of the same compound and expressly teaches the compound in its free-base form present as the monophosphate salt. For example, Ribeiro discloses 3-40 wt.% drug substance present as the monophosphate salt in multiple embodiments (¶[0090], ¶[0094], and ¶[0108]), 10-95 wt.% cellulose, lactose and/or mannitol (¶[0097] and ¶[0111]), and 0.2-2 wt.% magnesium stearate (¶[0112]).
Ribeiro additionally provides a lower-drug-load formulation consisting of 3-15 wt.% infigratinib monophosphate (¶[0115]), 75-95 wt.% cellulose, lactose and/or mannitol (¶[0118]), and 0.2-2 wt.% magnesium stearate (¶[0119]). For higher drug loading, Ribeiro additionally teaches 30-45 wt.% monophosphate (¶[0122] and ¶[0129]), with 35-65 wt.% or 45-65 wt.% cellulose, lactose and/or mannitol (¶[0125] or ¶[0132], respectively), and 0.2-2 wt.% magnesium stearate (¶[0126] and ¶[0133]). Ribeiro’s Example 1.1 expressly identifies 11.75 mg “Compound as monophosphate” for a 10-mg dosage strength and states that “[t]he salt factor is 1.175.” (¶[0146], Example 1.1 and table footnote).
Thus, Ribeiro establishes that when the therapeutic dose is expressed as free-base-equivalent infigratinib, use of the disclosed monophosphate results in a drug-substance mass equal to approximately 1.175 times the free-base amount. Accordingly, combining WO ’034’s expressly disclosed 0.1 mg amount with Ribeiro’s known monophosphate and salt factor gives 0.1 mg × 1.175 = 0.1175 mg (i.e., about 0.12 mg infigratinib monophosphate). Likewise, 1.0 mg × 1.175 = 1.175 mg (i.e., about 1.2 mg infigratinib monophosphate). These calculations are not asserted to be express disclosures of WO ’034, rather, they are the predictable consequence of employing Ribeiro’s expressly taught monophosphate salt for the low infigratinib amounts expressly disclosed by WO ’034.
Zhang teaches pediatric compressed minitablets
Zhang describes minitablets as an age-appropriate pediatric dosage-form option and explains that the format permits flexible adjustment of pediatric doses (p. 3590, Abstract). Zhang’s identifies the tableting excipients mannitol, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate (p. 3591, Materials). The Minitablets Manufacturing section describes compressed minitablets produced with 2 mm tooling (2 mm diameter and height), having a tablet weight of approximately 6.5 mg, and employs a process including dry blending, roller-compaction/dry granulation, and compression (p. 3591, Minitablets Manufacturing). Zhang therefore supplies a known pediatric compressed-minitablet configuration having essentially the claimed 2 mm dimension and approximately 7 mg mass, as well as the particular MCC/mannitol/croscarmellose/lubricant excipient architecture.
Omari teaches about 11 mg minitablets and conventional formulation proportions
Omari teaches esomeprazole minitablet formulations containing approximately 1.6-1.8 mg active ingredient in approximately 10.5-10.7-mg minitablets, corresponding to approximately 15.3-16.9 wt.% active ingredient, together with approximately 73.7-74.2 wt.% filler comprising Avicel®/MCC and lactose, approximately 5.6-7.5 wt.% fast-disintegrating material, and approximately 0.5 wt.% magnesium stearate (p. 157, Table 1). The minitablets have a diameter of between 2 and 3 mm (p. 156, last ¶). Thus, Omari is relied upon for conventional minitablet weight, dimension, drug-loading, filler, disintegrant, and lubricant proportions, not for infigratinib itself.
Quazi teaches high-filler/low-drug minitablets, croscarmellose, lubricant, and capsules
Quazi teaches a mini-tablet-filled capsule system and reports formulations containing approximately 1.5-4 wt.% terbutaline sulfate, approximately 88.5-93.6 wt.% total filler, disintegrant concentrations extending to approximately 7.2 wt.%, including croscarmellose sodium, and magnesium stearate, with the minitablets subsequently filled into capsules (p. 7, Table 1). Quazi is expressly directed to a “Design, Development and Optimization of Mini-Tablet Filled Capsule System” (p. 1, Title).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date, seeking to formulate infigratinib for treatment of FGFR3-related skeletal disease, that infigratinib could be administered in an oral tablet, that pharmaceutical compositions could contain amounts including 0.1 mg and 1.0 mg, and that infigratinib could be formulated as a salt from the teachings of WO ’034 (as outlined above). US ’560 independently supplies a reason to adapt the oral formulation for a child, because US ’560 expressly teaches oral administration (¶[0098]), adjustment according to age and weight (¶[0099]), and treatment of a child (¶[0101]).
A formulator of ordinary skill in the art would have had reason to employ Ribeiro’s specific monophosphate salt, because Ribeiro concerns pharmaceutical formulations of the same drug and expressly identifies that salt and compatible pharmaceutical excipients (¶[0090], ¶ [0094], ¶[0108], ¶[0115]; Example 1.1, and ¶[0146]).
Having been taught by WO ’034 and US ’560 to provide a low-dose oral infigratinib formulation for pediatric treatment, one of ordinary skill in the art would have looked to known pediatric solid-dosage-form technology such as Zhang. Zhang expressly identifies a pediatric compressed minitablet configuration of approximately 2 mm and approximately 6.5 mg and uses conventional tableting excipients (Abstract, Materials, and Minitablets Manufacturing).
One of ordinary skill in the art would further have looked to teachings of known working ranges of filler, disintegrant and lubricant in minitablets and for the conventional presentation of minitablets within capsules, such as those supplied by Omari and Quazi, and optimized these teachings substituting infigratinib monophosphate as the active ingredient.
The approximately 6.5 mg teaching closely approaches “about 7 mg”, and the instant claimed approximately 2 mm dimension is directly taught. No evidence establishes that a 7.0 mg rather than approximately 6.5 mg minitablet produces a critical or unexpected result. Ribeiro teaches cellulose, lactose and/or mannitol in formulations of infigratinib monophosphate and Zhang expressly employs microcrystalline cellulose and mannitol (as detailed above). Accordingly, mannitol, MCC, or their combination would have been obvious known filler selections.
Thus, the rejection is not based on an assertion that any drug can simply be placed in any dosage form. The references provide the following articulated sequence: WO ’034 teaches low dose infigratinib oral tablets and salt forms; US ’560 teaches oral administration of infigratinib (BGJ398) to a child and age/weight-dependent formulation; Ribeiro teaches infigratinib monophosphate and filler/lubricant ranges; Zhang teaches pediatric compressed minitablets of 2 mm dimensions and 6.5 mg weight using MCC, mannitol, and croscarmellose; Omari and Quazi teach additional conventional minitablet composition ranges and capsule presentation.
Regarding the overlapping ranges, the quantitative disclosures independently reinforce the conclusion of obviousness with Ribeiro’s 3-15 wt.% monophosphate (¶[0115]), overlapping claims directed to 1-9 wt.% and 10-20 wt.%; 3-40 wt.% monophosphate (¶[0090], ¶[0094], and ¶[0108]), encompassing 10-20 wt.% and 15-20 wt.%; 75-95 wt.% cellulose/lactose/mannitol (¶[0118]), overlapping 85-95, 90-95, 60-80, and 65-80 wt.% filler ranges; and 0.2-2 wt.% magnesium stearate (¶[0112], and ¶[0119]), encompassing 0.25-1 wt.% lubricant; Omari’s approximately 15.3-16.9 wt.% active, 73.7-74.2 wt.% filler, 5.6-7.5 wt.% disintegrating material, and 0.5 wt.% magnesium stearate (p. 157, Table 1); Quazi’s approximately 1.5-4 wt.% active, 88.5-93.6 wt.% filler, and disintegrant concentrations extending to approximately 7.2 wt.% (Table 1); and Zhang’s 6.5 mg, 2 mm minitablet (p. 3591), closely approaching the claimed approximately 7 mg, 2 mm configuration.
Where prior art and claimed ranges overlap, a prima facie case of obviousness generally exists absent persuasive evidence of criticality or unexpected results (see In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003)). Where the general conditions are disclosed, determination of optimum or workable values through routine experimentation ordinarily does not confer patentability (see In re Aller, 220 F.2d 454, 456 (CCPA 1955)). No evidence presently establishes that the claimed numerical endpoints correspond to critical boundaries producing unexpected results commensurate with the full scope of the claims. Accordingly, it would have been obvious before the effective filing date to implement WO ’034’s expressly contemplated low-dose infigratinib oral tablet for the pediatric treatment taught by US ’560 using Ribeiro’s known monophosphate formulation chemistry and the known pediatric minitablet architectures and conventional formulation ranges taught by Zhang, Omari, and Quazi.
Regarding the “made using dry granulation” limitation of instant claims 42, 49, 53, 63, 67, 161, 168, 181, and 188, Zhang expressly teaches a minitablet-manufacturing process involving dry granulation/roller compaction followed by compression using approximately 2 mm tooling (Zhang, p. 3591, Minitablets Manufacturing).
The process language in the present claims, however, appears in product claims to a minitablet, solid dosage form, or compressed pharmaceutical composition “made using dry granulation.” Thus, the recitations are product-by-process limitations. Under In re Thorpe, 777 F.2d 695, 698 (Fed. Cir. 1985), patentability of a product-by-process claim is based on the product itself. Where the resulting product is the same as or obvious from the prior-art product, a different manufacturing process does not render the product patentable absent a structural distinction attributable to the process.
Here, the underlying infigratinib-monophosphate minitablet products are rendered obvious for the reasons discussed above, and the claims do not recite a structural characteristic of the finished product that results uniquely from dry granulation. Zhang additionally establishes that dry granulation was a known method for making compressed minitablets. Accordingly, absent evidence that dry granulation produces a structurally different claimed product, the “made using dry granulation” limitation does not distinguish instant claims 42, 49, 53, 63, 67, 161, 168, 181, and 188.
Nevertheless, Ribeiro must be considered together with the remainder of the prior art. Ribeiro’s contrary disclosure concerning infigratinib is acknowledged and considered. Ribeiro expressly states that mechanical stress during roller compaction generated degradation products and teaches avoidance of substantial compression/compaction (¶[0066]). Ribeiro specifically identifies roller compaction and tablet compression as examples of substantial mechanical stress.
However, the present rejection does not rely on Ribeiro as providing the motivation to compress infigratinib. Ribeiro is relied upon for its disclosure of the monophosphate salt, quantitative drug/filler/lubricant ranges, and particular excipients. Second, WO ’034, published later than Ribeiro, expressly identifies infigratinib oral tablets as suitable unit administration forms. Thus, as of the effective filing date, the prior-art record did not contain only Ribeiro’s preference for a compression-free formulation, it also contained a later same-drug reference expressly directing the artisan to an infigratinib tablet.
Third, Ribeiro demonstrates that mechanical compression presented a stability disadvantage, but it does not establish an inability to produce compressed material. Ribeiro reports generation of degradation products rather than failure to form a pharmaceutical product (¶[0066]). Fourth, the pending claims do not require a maximum level of aniline or aminopyrimidine degradant, a particular stability specification, a minimum shelf life, or “little or no degradation.” Consequently, the alleged surprising ability of applicant’s examples to minimize degradants is not itself a limitation of the rejected claims. Accordingly, Ribeiro’s teachings have been considered but does not overcome the prima facie case based upon the instant claims as presently drafted.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 08 July 2026, have been fully considered.
The applicant argues that Mitsui, published 15 January 2022, postdates the 18 December 2020 effective filing date and cannot supply a motivation that did not exist before the effective filing date.
A later reference may not be used to reconstruct the pre-filing state of the art or provide a substantive motivation to modify prior art where that motivation was not otherwise established as of the effective filing date. The examiner acknowledges and was fully aware that Mitsui is published after the earliest effective filing date and therefore is not available as prior art under 35 U.S.C. § 102(a)(2) or § 103. Mitsui was previously relied upon as an evidentiary reference to establish a material property of minitablets- improved pediatric swallowability (see MPEP § 2124, permitting post-filing references to establish a universal scientific fact, a known material property, or the level of ordinary skill around the relevant time). Nevertheless, the empirical finding in Mitsui regarding swallowability of the presently claimed minitablet dosage form in children 6-23 months old is withdrawn and is not relied upon as evidence supplying the motivation to combine in any way.
This determination does not, however, remove the pre-filing teachings of Zhang concerning pediatric minitablets. The motivation to formulate minitablets of the claimed size (about 2 mm, 7 mg) for pediatric use is independently taught by the prior art of record, namely Zhang. Zhang explicitly teaches that minitablets of 2 mm diameter and 6.5 mg weight are suitable for pediatric applications, enabling flexible dose adjustment. This reference alone provides a clear teaching and motivation to scale down a low-dose pediatric formulation to minitablets of the claimed dimensions and weight. The rejection under 35 U.S.C. § 103 is therefore does not have any reliance on Mitsui.
The applicant’s statement that US ’560 provides no relevant pediatric/oral teaching is not persuasive. US ’560 expressly teaches pharmaceutically acceptable carriers and excipients, expressly states that the oral route can be used, explains that dosage varies according to the age and weight of the patient, and states that the human subject is preferably a child and that treatment may occur during the child’s growth period.
US ’560 therefore provides a legitimate pre-filing teaching of pediatric oral administration of infigratinib (BGJ-398). The applicant is correct, however, that US ’560 does not itself disclose the presently claimed minitablet dimensions, minitablet weight, or the specific claimed formulations, which are addressed by the combined teachings of the cited prior art, as outlined above.
The previous action characterized WO ’034 as expressly teaching “infigratinib monophosphate.” That characterization should be corrected. WO ’034 teaches oral tablets, gel capsules, powders, and granules, and identifies compositions containing, among other amounts, 0.1 mg and 1.0 mg active ingredient. WO ’034 also states that infigratinib can be present in neutral or salt form and lists salts formed with phosphoric acid. WO ’034 therefore supports oral dosage forms, low dosage amounts, and a generic phosphate-salt concept, but it does not expressly disclose the specific infigratinib monophosphate limitation in the manner stated in the prior action.
The applicant’s reliance on Ribeiro (US 10,278,969/US20170007602), has been considered as part of the total prior-art record. The applicant specifically relies upon Ribeiro’s disclosure that mechanical stress caused degradation and that compression and compaction should be avoided.
However, Ribeiro is materially more than a reference expressing a mere preference for one conventional manufacturing alternative over another. Ribeiro identifies the drug expressly as including the monophosphate salt and teaches that mechanical stress during dry compaction, including roller compaction, produced hydrolysis degradation products. Ribeiro states that “compaction/compression involving mechanical stress should be avoided.” Ribeiro further identifies roller-compaction forces and conventional tablet-compression forces as examples of the substantial mechanical stress the disclosed process seeks to avoid.
This teaching by Riberio has been considered as part of the obviousness inquiry along with the totality of the art, as instructed under MPEP § 2145. Accordingly, the prior rejection’s reasoning, that a skilled artisan would simply use Zhang’s roller compaction and compression as a matter of routine formulation optimization, does not adequately address the compound-specific instability teaching of Ribeiro.
A reference that criticizes, discredits, or otherwise discourages the claimed path is materially different from a reference that merely identifies another alternative as preferable. Ribeiro addresses a specific problem of mechanical stress-induced degradation during roller compaction for a particular formulation of infigratinib free base and certain salts. The reference cautions against “substantial mechanical stress by any compression and/or compaction process step” in the context of its own process, but it does not constitute a categorical prohibition against compression of infigratinib monophosphate under all conditions. The reference itself acknowledges that the degradation issue was surprising and related to specific forces; it does not demonstrate that compression of infigratinib monophosphate with the excipients and process of the claimed invention would have been impossible or discouraged.
The prior art of record, particularly Zhang, teaches a routine dry granulation (roller compaction) and compression process for minitablets containing mannitol, microcrystalline cellulose, croscarmellose sodium, and a lubricant. This process is directly applicable to a wide range of active pharmaceutical ingredients. One of ordinary skill in the art, faced with the need to formulate a low-dose pediatric minitablet of infigratinib, would have been motivated to apply the established minitablet manufacturing techniques of Zhang.
The artisan would have reasonably expected that any potential degradation could be managed through routine optimization of excipients (e.g., use of protective fillers, adjustment of compression force) because the art recognized that many sensitive compounds are successfully compressed using dry granulation with appropriate excipient selection. Ribeiro does not teach that the alleged problem is insurmountable and stable compressed compositions cannot be made by routine dry granulation.
A teaching away requires a clear and unmistakable direction in the prior art that the claimed invention would not work or is not desirable. Ribeiro’s caution, is limited to its specific process conditions and does not address the minitablet formulation of the present claims. Thus, Ribeiro does not constitute a clear teaching away from the claimed compressed minitablets.
The combination of references provides a reasonable expectation of success because the artisan would have been motivated to apply the well-established minitablet process of Zhang to infigratinib, and the potential degradation issue would have been seen as controllable through routine excipient and process optimization. Accordingly, the teaching away argument does not rebut the prima facie case of obviousness.
Conclusion
No claims are allowed.
The 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 (87 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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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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