DETAILED ACTION
Status of Claims
The amendment submitted August 10, 2026 has been entered.
Claims 1-8, 10-17, and 19-22 are pending and under consideration.
Claims 7 and 16 are presently amended.
Claims 9 and 18 are cancelled.
Claims 21-22 are withdrawn in the instant office action as explained below in the Election/Restriction section.
Claims 1-8, 10-17, and 19-20 are under consideration in the instant office action as explained below in the Election/Restriction section.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8, 10-17, and 19-20 drawn to a powder and oral solution comprising ribociclib succinate in the reply filed on August 10, 2026 is acknowledged.
Applicant’s election without traverse of Table 8 on pages 22-23 of the specification in the reply filed on August 10, 2026 is likewise acknowledged.
Claims 1-8, 10-17, and 19-20 read on the elected species.
For the purposes of compact prosecution, the search was expanded. Applicant should not construe this to indicate the full scope of the claims has been searched.
Claims 21-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 30, 2026
Claims 1-8, 10-17, and 19-20 are under consideration and the subject of this Office Action.
Priority
This application is a 371 National Phase Application of PCT/EP2022/079833 filed January 23, 2023, which claims the benefit of priority to Indian Patent Application No. IN202211004186, filed on January 25, 2022.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d), and the certified copy has been filed.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Two information disclosure statements (IDS) submitted on July 22, 2024 and August 10, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Abstract Objections
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 103
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 non- obviousness.
Claims 1-8, 10-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Rampalli et al. (USPN 11,111,250 B2) in view of Anderson et al. (Anderson et al. 2006. Excipients for oral liquid formulations. Excipient development for pharmaceutical biotechnology, and drug delivery systems, pp.155-180), Van der Merwe et al. (Van der Merwe, J., Steenekamp, J., Steyn, D. and Hamman, J., 2020. The role of functional excipients in solid oral dosage forms to overcome poor drug dissolution and bioavailability. Pharmaceutics, 12(5), p.393), Ulrich et al. (USPN 6,806,256 B2), and Jadhav et al. (Jadhav, N.R., Paradkar, A.R., Salunkhe, N.H., Karade, R.S. and Mane, G.G., 2013. Talc: A versatile pharmaceutical excipient. World J. Pharm. Sci, 2(6), pp.4639-4660).
Regarding claims 1-2, Rampalli teaches “a powder for oral solution,” which comprises the identical elements as instant claims 1-2: ribociclib succinate, one or more diluents, one or more solubilizers, one or more preservatives, one or more anti-adherents, one or more glidants, one or more sweeteners and a flavor.
Specifically, Rampalli teaches “Pharmaceutically acceptable excipients used in the compositions comprising substantially pure crystalline or amorphous form of Ribociclib or its succinate salt obtained as per the present application process—include, but are not limited to diluents such as starch, pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, di-calcium phosphate, tri-calcium phosphate, mannitol, sorbitol, sugar and the like; binders such as acacia, guar gum, tragacanth, gelatin, pre-gelatinized starch and the like; disintegrants such as starch, sodium starch glycolate, pregelatinized starch, Croscarmellose sodium, colloidal silicon dioxide and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants, waxes and the like. Other pharmaceutically acceptable excipients that are of use include but not limited to film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants and the like (column 12, lines 45-64).”
Regarding claim 3, as aforementioned Rampalli teaches the elements of claim 3 “wherein the one or more diluent(s) is mannitol.”
Regarding claim 7, as aforementioned Rampalli teaches the elements of claim 7 “wherein the one or more glidant(s) is colloidal silica.”
Rampalli also teaches “In one embodiment of the present invention, it also includes premix comprising one or more pharmaceutically acceptable excipients in the range of 1 to 50% w/w with the substantially pure crystalline or amorphous form of Ribociclib or its succinate salt, while retaining the crystalline nature of the premix (column 12, lines 26-31),” which overlaps and/or is within the range of excipients as claimed in instant invention.
Rampalli does not explicitly teach the exact amounts as per claims 1-2, and 19.
However, as per MPEP 2144.05. I.: 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).
Rampalli also does not teach the elements of claim 3 where the solubilizer is tartaric acid, the elements of claim 5 where the preservative is sodium benzoate, the elements of claim 6 where the anti-adherent is talc, and the elements of claim 8 where the sweetener is saccharin sodium.
Claim 10 only differs from claim 1 as it is directed towards an oral solution. Consequently, similar evidence and arguments as already presented are applied as set forth above regarding excipients.
Rampalli teaches that “In another embodiment, the substantially pure crystalline or amorphous form of Ribociclib or its succinate salt obtained by the processes of the present application may be formulated as solid compositions for oral administration in the form of capsules, tablets, pills, powders or granules. In these compositions, the active product is mixed with one or more pharmaceutically acceptable excipients. The drug substance can be formulated as liquid compositions for oral administration including solutions, suspensions, syrups, elixirs and emulsions, containing solvents or vehicles such as water, sorbitol, glycerin, propylene glycol or liquid paraffin (column 12, lines 14-25).”
Consequently, Rampalli teaches both powders and oral solutions, including the use of an aqueous vehicle as per claim 10.
Similar to the claims already mentioned, regarding claim 12, as aforementioned Rampalli teaches the elements of claim 12 “wherein the one or more diluent(s) is mannitol.”
Regarding claim 16, as aforementioned Rampalli teaches the elements of claim 16, “wherein the one or more glidant(s) is colloidal silica.”
Rampalli does not explicitly teach the exact amounts as per claims 11-17, and 20. However, as mentioned above, Rampalli does teach a range for excipients which overlaps and/or is within the range of excipients as claimed in instant invention.
Similarly, as aforementioned, Rampalli also does not teach the elements of claim 13 where the solubilizer is tartaric acid, the elements of claim 14 where the preservative is sodium benzoate, the elements of claim 15 where the anti-adherent is talc, and the elements of claim 17 where the sweetener is saccharin sodium.
Anderson teaches the benefits of oral liquid formulations: “Compared to conventional tablets and capsules, oral liquid dosage forms including solutions, syrups, suspensions, elixirs, or concentrates offer unique advantages to many patients. For example, liquids may provide better patient compliance for those with swallowing difficulties and better dosage control versus a fixed tablet dose (page 155, paragraph 1).”
Anderson furthermore teaches that “Many companies use a rapid high-throughput screening approach to determine the optimal combination of excipients for their formulation.”
Consequently, it is reasonable to conclude that such a process is part of routine optimization as is standard in the art of pharmaceutical science in developing different formulations based on benefits and features desired.
Figure 2 of Anderson as shown below also demonstrates common excipients and their overlapping functions in oral formulations.
PNG
media_image1.png
286
398
media_image1.png
Greyscale
Consequently, Anderson teaches that oral liquids comprise the common excipient classes as claimed in instant invention, and also that such excipients can be multifunctional.
Anderson further teaches that “Microbiological contamination presents a significant health hazard in oral liquids. Therefore, the use of preservatives plays an important role in the stability of oral liquid formulations by circumventing the growth of microorganisms during the pro duct’s manufacture and shelf life.”
Anderson further teaches that “Choosing an acceptable preservative when developing an oral liquid formulation is primarily limited by the number of approved excipients. As Table 10 demonstrates, there are many preservatives listed in the FDA inactive ingredient guide for dosage forms other than oral liquids; however not many have been commonly used in oral solutions or suspensions,” and further teaches sodium benzoate as one of the limited approved excipients as listed in Table 10.
Table 11 of Anderson teaches tartaric acid as an acidulant, antioxidant and sequestering agent. As aforementioned, excipients in oral formulations are known to have overlapping functions.
Figure 1 of Van der Merwe teaches that there are different classes of multifunctional excipients that influence solubility and bioavailability of APIs.
PNG
media_image2.png
525
550
media_image2.png
Greyscale
Van der Merwe teaches that tartaric acid is a pH adjusting excipient as supported by Anderson, and that such property is used to improve dissolution and solubility of drugs.
Specifically Van der Merwe teaches that “Examples of pH-adjusting excipients that can be used to improve the dissolution rate of weak basic drugs include organic acids (e.g., citric acid, tartaric acid and carbonic acid). After disintegration of a solid dosage form, the organic acid dissolves in the surrounding gastric juices and lowers the pH of the stagnant diffusion layer surrounding each drug particle, creating a desirable environment for the dissolution and consequently the absorption of alkaline drugs.”
Finally Van der Merwe teaches that “Various approaches can be followed or employed to improve the dissolution of a poorly soluble API in a solid oral dosage form ranging from incorporation of functional excipients to techniques such as preparation of solid dispersions and micronisation of the API particles. Examples of excipients that can increase an API’s solubility and dissolution rate include cyclodextrins, disintegrants, pH-adjusting excipients, natural polymers, surfactants, co-surfactants, oils/lipids and sugars.”
Consequently, tartaric acid is well-known in the pharmaceutical arts as a multifunctional excipient, one of whose functions is to improve dissolution and solubility of API.
Ulrich teaches that “Orally administered drugs are provided to the patient in many dosage forms, including solid forms such as capsules, caplets or tablets and liquid forms such as solutions, syrups, emulsions or suspensions. Pharmaceutically active agents administered in solid dosage form are usually intended to be swallowed whole. The disagreeable taste of the drug is generally not of concern when formulating oral solid dosage forms, because the pharmaceutical's taste can be easily masked with an exterior coating.”
Ulrich further teaches that “A common formulation problem associated with liquid pharmaceutical dosage forms (such as solutions (including syrups) or suspensions) is masking the disagreeable taste that a pharmaceutically active agent may often manifest when administered in a liquid dosage form.”
Ulrich further teaches that “Saccharin is used to enhance flavor systems and to mask some unpleasant taste characteristics and has approximately 500 times the sweetening power of sucrose. The taste masking effective amount of saccharin has a range of from about 0.08 to about 3 grams per 100 mL.
Saccharin sodium is considerably more soluble in water than saccharin, is used more frequently in pharmaceutical formulations and has approximately 300 times the sweetening power of sucrose. The taste masking effective amount of saccharin sodium has a range of from about 0.1 to about 5 grams per 100 mL.”
Consequently, Ulrich teaches the motivations to use a sweetener in a liquid dosage and that saccharin sodium is used more frequently in pharmaceutical formulations as it has superior water solubility properties.
Jadhav teaches that “The percentage of talc used in the design of various dosage forms varies. It fulfills all the criteria of the glidant and diluent. For decades, it has been used as a pharmaceutical aid (dusting powder), an excipient and filler for pills, tablets and for dusting tablet molds. It is also used as an anti-caking agent and lubricant in tablet making. However, it is widely used as a dissolution retardant in the development of controlled-release products and as a novel powder coating for extended-release pellet making. Moreover, it has been included in the Food and Drug Administration (FDA) inactive ingredients guide (buccal tablets, rectal and topical preparations) and in the non-parenteral medicines licensed in the UK.”
Consequently, Jadhav teaches that talc is another commonly used multifunctional excipient, well-known to have anti-caking or anti-adherent properties.
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified Rampalli’s invention because Rampalli teaches that Ribociclib succinate can be formulated as a liquid composition including as an oral solution for oral administration using excipients in a range that includes the amounts of instant invention and because Rampalli teaches the components of said oral solution and solid powder, including mannitol and colloidal silica. Anderson teaches motivations to develop an oral solution such as being beneficial to patients with swallowing difficulties and additional teaches that developing such formulations can be achieved as routine optimization using rapid high-throughput screening. Anderson additionally teaches that many of the excipients can be multifunctional, and to that aim tartaric acid can function in helping with solubility and as an antioxidant, sodium benzoate is a commonly used preservative of which there are limited FDA approved substances. Van der Merwe additionally teaches the multifunctional nature of excipients and that tartaric acid can help improve solubility. Ulrich teaches that it is common to use a sweetener to mask unpleasant taste of drugs, and that saccharin sodium is superior based on its improved water solubility. Finally, Jadhav teaches that talc is a highly commonly-used excipient used as an anti-caking and/or anti-sticking agent.
Consequently, a person of ordinary skill in the art of pharmaceutical sciences would be motivated to modify Rampalli based on developing an oral solution for patient populations that struggle with swallowing solid dosages. Therefore, as emphasized by Anderson, an ordinarily skilled artisan would arrive at instant invention as a predictable result with a reasonable expectation of success via routine optimization based on what is known in the art for formulation sciences and based on the teachings as aforementioned with regards to commonly used excipients in developing oral solutions and powders for oral solutions.
It would have been further prima facie obvious to optimize the excipients and excipient amounts to arrive at the specific ranges disclosed in instant invention as it is well-known that such tasks are achieved via rapid high-throughput optimization as predictable results with reasonable expectations of success in developing new pharmaceutical formulations based on desired administration mode.
As per MPEP 2144.05. II. A: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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).” Applicant has not provided any evidence supporting criticality of ranges.
Consequently, a person of ordinary skill in art would arrive at instant invention as a predictable results with a reasonable expectation of success based on the beneficial teachings of Rampalli, Anderson, Van der Merwe, Ulrich and Jadhav.
Therefore, Claims 1-8, 10-17, and 19-20 are rejected on grounds of obviousness.
Conclusion
Claims 1-8, 10-17, and 19-20 are under consideration and are rejected. No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights