DETAILED ACTION
This office action is in response to applicant’s filing dated November 5, 2025.
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 .
Status of Claims
Claims 1 and 6 – 8 are pending in the instant application. Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on November 5, 2025 are acknowledged. Acknowledgement is made of Applicant's amendment of claim 1 and cancelation of claims 2 – 5 and 9 - 18.
Claims under consideration in the instant office action are claims 1 and 6 – 8.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/05/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on November 5, 2025, have been fully considered.
Acknowledgement is made of the Applicant’s amendment of claim 1 to include limitations of claim 5. The amendments as shown herein: “[…]wherein the compound of Chemical Formula 1 or the pharmaceutically acceptable salt thereof is included in the pharmaceutical preparation in an amount of 2.0% or more and less than 20% by weight based on the total weight of the pharmaceutical preparation and wherein the diluent is a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1 and is included in the pharmaceutical preparation in an amount of 20% to 50% by weight based on the total weight of the pharmaceutical preparation”.
Acknowledgement is made of the Applicant’s cancellation of claims 2 – 5 and 9.
Accordingly, the rejection under 35 U.S.C. §102 of claims 1-4, 6-8 and 10-13 as anticipated by Kim’452, as well as the rejection of claim 9 as anticipated by Kim’022 is withdrawn.
For the same reason the rejection of claims 3, 4 and 9 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 9,931,406 B2 and U.S. Patent No. US 9,731,022 B2 is withdrawn.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
Claim Interpretation
The claim 1 language “[…]a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1” was interpreted as in a weight ratio of mannitol to microcrystalline cellulose of 0.50:1 to 3.2:1 respectively.
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 1 and 6 – 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US 2013/0071452 A1, cited in IDS, filed 07/01/2025, hereinafter Kim’452) in view of Li et al (US 8,932,629 B2, hereinafter Li).
Instant claims are drawn to a pharmaceutical preparation comprising a granule comprising a compound of formula 1
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or a pharmaceutically acceptable salt thereof and a diluent, where the diluent is a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1 respectively, where the compound of formula 1 presents in the amount of 2.0% or more and less than 20% by weight based on the total weight of the pharmaceutical preparation and where diluent mixed with granule in the amount of 20% to 50% by weight based on the total weight of the pharmaceutical preparation. Said pharmaceutical composition further comprises glidant such as magnesium stearate in an amount of 0.5% to 1.5% by weight based on the total weight of the pharmaceutical preparation.
Kim’452 teaches a pharmaceutical composition comprising compound of formula (I)
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(page 2, [0013]) and at least one excipient such as a diluent, a binder, a disintegrant, and a lubricant. A diluent may be microcrystalline cellulose or mannitol (page 3, [0034]). The pharmaceutical composition of Kim’452 can be formulated for oral administration such as a tablet, a capsule or granules (page 3, [0036]). According to the exemplary preparation procedure, taught by Kim’452, additives were added to a wet granule mixture of compound of formula (I) and mannitol. The final mixture also contained magnesium stearate. The total weight of the dry composition is 210 mg of which: 8 mg is a compound of formula (I), 98 mg is mannitol and 2 mg is magnesium stearate (page 3, [0039] and Table 1). Based on the total weight (210 mg) of the pharmaceutical composition of Kim’452, the compound of formula (I) is ~ 3.8% (8 mg), mannitol is ~ 46.7% (98 mg) and magnesium stearate is ~ 0.95% (2 mg). All the amounts taught by Kim’452 are within the range of the amounts of corresponding components of pharmaceutical preparation, required by instant claims. MPEP 2131.03 (I) states: "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).
Kim’452 is silent about the pharmaceutical composition where the diluent is a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1. However, Li teaches a pharmaceutical compositions for preparation of solid dosage forms such as tablets, where microcrystalline cellulose (MCC) co-processed with a sugar alcohol, such as mannitol, and then used in tablet formulations (column 1, lines 17 – 24). Li describes advantageous properties such as compactability and other desirable functional properties for the preparation of tablets when MCC co-processed with a sugar alcohol, than MCC or a sugar alcohol when used alone (column 2, lines 39 – 45). Li teaches the weight ratio of the said two components of about 99:1 to 1:99 microcrystalline cellulose:sugar alcohol. In example 2, Li illustrates co-processed MCC/sugar alcohol samples with 25%, 50% and 75% mannitol (column 10, example 2 and Table 1). The weight ratios of MCC/mannitol taught by Li, fall within the ranges of these components required by instant claims (e.g. 75% of mannitol and 25 % of MCC, taught by Li, equivalent to a 3:1 ratio of instant claims). MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Thus, since Kim’452 teaches pharmaceutical composition comprising compound of formula (I) and a diluent such as mannitol or microcrystalline cellulose, Li teaches tablet formulations where mannitol and microcrystalline cellulose taken in combination to improve certain properties of tablet, where examples demonstrate relationship between certain physical properties of tablet and weight ratio of MCC/mannitol, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine teachings of Kim’452 and Li to arrive at a claimed pharmaceutical preparation. The one of ordinary skills would be motivated to do so in search of an improvement of desired properties of tablet or other solid dosage form with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- Kim teaches a pharmaceutical composition with an improved stability, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and the pharmaceutically acceptable additives such as a diluent, a binder or a disintegrant, where diluent is microcrystalline cellulose or mannitol, Kim does not teach a mixture of mannitol and microcrystalline cellulose (MCC);
- Kim provides no motivation to change said pharmaceutical preparation;
- Even if the skilled person had considered modifying the pharmaceutical preparation of Kim, the skilled person would not have had any specific reason to select the extra-granular phase for modification, or modify the extra-granular phase by adding microcrystalline cellulose (MCC) or by using the specific amounts of poziotinib and diluent and the specific ratio of mannitol to MCC recited in amended claim 1;
- In the knowledge that poziotinib is subject to degradation and that this can be influenced by other components of the pharmaceutical preparation, the skilled person would have therefore adopted a conservative approach and refrained from modifying the composition of Kim;
- Li teaches advantages of co-processed MCC/mannitol versus dry blended MCC/mannitol, whereas the present claims recite the use of dry blend of MCC and mannitol; thus, Li teaches directly away from such a mixture;
- present invention is intended to provide a pharmaceutical preparation having high productivity due to improved tableting properties, friability and mass uniformity, and high stability due to a low generated amount of impurities even under severe conditions, especially knowing the difficulties in formulating pharmaceutical compositions comprising the compound of Chemical Formula 1 (poziotinib);
- it would not have been obvious for the skilled person to provide the claimed pharmaceutical preparation, nor would they have been able to do so with a reasonable expectation of success in view of the cited art.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive
because: as set forth above Kim teaches the same pharmaceutical composition, known for the same purposes as instantly claimed. The formulation, disclosed by Kim is aimed to be of improved stability, considering the fact that poziotinib (active ingredient of said formulation) is prone to degradation. Kim suggests mannitol or MCC as the formulation excipients. Merely not exemplifying the formulation where mannitol is mixed with MCC does not teach away from taking those additives in a mixture. Li teaches tablet formulations, where an excipient is a mixture of MCC with sugar alcohol, such as mannitol. Li teaches formulations where mannitol is dry blended or co-processed with MCC. Thus, Li teaches both ways (dry blend or co-processed) of preparing formulations. Li does not teach away from instantly claimed formulation, since Li discloses the same excipient, taken in the same weight ranges and seeks the same improved characteristics for the tablet formulations as instantly claimed formulation. As such, Li teaches: “The excipients should not accelerate chemical and/or physical degradation of the active and should not interfere with its biological availability. They[excipients] should show low lubricant sensitivity and ensure acceptable active content uniformity” (column 7, 2nd paragraph).
Thus, combined prior art teaches the same formulation, prepared by slightly different process. MPEP 2113 states: Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).
Regarding the argument about expectation of success, it is not found persuasive because, reasonable expectation of success is not equivalent to predictability. MPEP 2144.08 states:[…]However, obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).
Taking into account all said above, the instant invention as a whole is considered obvious over teachings of prior art.
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 1 and 6 – 8 as obvious over teachings of Kim and Li is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1, 8 and 9 of U.S. Patent No. US 9,931,406 B2, and
claims 1, 4 and 5 of U.S. Patent No. US 9,731,022 B2, in view of Li et al (US 8,932,629 B2).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are directed to a pharmaceutical preparation comprising a granule comprising a compound of formula 1
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or a pharmaceutically acceptable salt thereof and a diluent, where the diluent is a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1 respectively, where the compound of formula 1 presents in the amount of 2.0% or more and less than 20% by weight based on the total weight of the pharmaceutical preparation, and where diluent mixed with granule in the amount of 20% to 50% by weight, based on the total weight of the pharmaceutical preparation.
The claims of U.S. Patent No. US 9,931,406 B2 are directed to a pharmaceutical composition comprising a compound of formula (I)
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or a pharmaceutically acceptable salt thereof as an active ingredient, a non-metallic salt lubricant and a diluent, where diluent presents in an amount ranging from 20% to 95% by weight based on the total weight of the composition.
Similarly, the claims of U.S. Patent No. US 9,731,022 B2 are directed to a pharmaceutical composition comprising a compound of formula (I)
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or a pharmaceutically acceptable salt thereof as an active ingredient, a non-metallic salt lubricant and a diluent, where a diluent presents in an amount ranging from 20% to 95% by weight based on the total weight of the composition.
The pharmaceutical compositions described by named above patents, contain approximately 50% of mannitol (diluent) (columns 7 – 9, Tables 2 – 5). Thus, the amount of diluent disclosed by said patents lays within or overlaps with the instantly claimed ranges. MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Although, instant claims do not recite non-metallic salt lubricant in the composition as patented claims recite, the “comprising” claim language does not exclude additional, unrecited elements or steps.
The patented claims do not teach where the diluent is a mixture of mannitol and microcrystalline cellulose in a weight ratio of 0.50:1 to 3.2:1. However, Li teaches a pharmaceutical compositions for preparation of solid dosage forms such as tablets, where microcrystalline cellulose (MCC) co-processed with a sugar alcohol, such as mannitol, and then used in tablet formulations (column 1, lines 17 – 24). Li describes advantageous properties such as compactability and other desirable functional properties for the preparation of tablets when MCC co-processed with a sugar alcohol, than MCC or a sugar alcohol when used alone (column 2, lines 39 – 45). Li teaches the weight ratio of the said two components of about 99:1 to 1:99 microcrystalline cellulose:sugar alcohol. In example 2, Li illustrates co-processed MCC/sugar alcohol samples with 25%, 50% and 75% mannitol (column 10, example 2 and Table 1). The weight ratios of MCC/mannitol taught by Li, fall within the ranges of these components required by instant claims (e.g. 75% of mannitol and 25 % of MCC, taught by Li, equivalent to a 3:1 ratio of instant claims). MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Thus, since prior art teaches the same composition, known for the same purposes, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine teachings of prior art to arrive at claimed pharmaceutical preparation. The one of ordinary skills would be motivated to do so in search of an improvement of desired properties of tablet or other solid dosage form with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- Applicant maintains that the rejection is moot in view of the amendment to claim 1.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive
because: as set forth above, the amended claim 1 is not patentably distinct from previously granted claims in view of teachings of Li, as it teaches pharmaceutical formulation comprising the same active ingredient, where modification of excipients does not materially impact the product's functionality according to “comprising” claim language (see the rejection section above).
Therefore, applicant’s arguments are not persuasive and the rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 9,931,406 B2 and U.S. Patent No. US 9,731,022 B2 is maintained.
Conclusion
Claims 1 and 6 – 8 are rejected. No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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/E.V.V./Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691