DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments filed 2/17/2026 have been entered.
Claims 1-17 are pending.
Upon reconsideration, the outstanding rejection under 35 USC 112b is withdrawn in view of the arguments filed 2/17/2026.
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 nonobviousness.
Claim(s) 1-10, 12-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2022/0304983 (‘983) in view of Gaidhani et al., World Journal of Pharmaceutical Research, 4(8):516-543 (2015) and Öztekin et al., Journal of Pharmaceutical and Biomedical Analysis, 37 (2005) 1121–1124. ‘983 and Gaidhani et al. are references of record.
‘983 teaches a freeze-dried (lyophilized) composition comprising bendamustine and sulfobutyl-β-cyclodextrin (a.k.a. sulfobutylether-β-cyclodextrin or SBE-CD) in a ratio of about 1:7 (see page 9, Example 12). ‘983 teaches the composition can be used for cancer treatment (see claims 9, 19-20). ‘983 teaches the general range of weight ratio of bendamustine to cyclodextrin to be 1:5-1:100 (which is for mole ratio to be about 1:5-1:70 if the cyclodextrin is SBE-CD) (see claim 1 and 9 for example). ‘983 teaches the freeze drying procedures and conditions including the temperature and time which similar to what is claimed (see [0086]).
‘983 does not expressly teach the pressure used for the lyophilization process. ‘983 does not expressly teach the water content of the composition. ‘983 does not teach a cationic stabilizer.
Öztekin et al. teaches “Cationic surfactants composed of quaternary ammonium groups are extensively used as preservatives or antiseptic agents in industrial and commercial products. Due to their ability to stabilize emulsions and their antibacterial properties, surfactants used widely in cosmetics, hygiene products and some drugs are ingested by the human body.” (see page 1121, col. 1, first paragraph). Öztekin et al. teaches “The quaternary ammonium ions benzethonium (BZ) and cetylpyridinium (CP) are widely used as antimicrobial agents in the pharmaceutical preparations and cosmetics products.” (see page 1121, col. 2, last paragraph).
Gaidhani et al. teaches lyophilization is the most common process to produce composition when aqueous solution stability is an issue. It is central to the protection of materials, which requires low moisture content (less than 1%) (see page 517, second paragraph).
It would have been obvious to one of ordinary skill in the art at the time of filing to ensure the water content in the composition as less than 1%. It would have been obvious to one of ordinary skill in the art at the time of filing to employ the herein claimed pressure while freeze-drying. It would have been obvious to one of ordinary skill in the art at the time of filing to employ a cationic stabilizer in the composition.
One of ordinary skill in the art would have been motivated to ensure the water content in the composition as less than 1% because by lowering the water content in the composition, it will reduce the degradation of the composition and extend shelf life of the bendamustine composition.
Furthermore, one of ordinary skill in the art would have been motivated to employ the herein claimed pressure while freeze-drying. The pressure of lyophilization is a factor that can be controlled in order to achieve the optimal composition with minimum water content and thereby maximum stability. Therefore, adjusting the pressure of the lyophilization process would be reasonably expected to be effective in achieving a stable bendamustine composition.
One of ordinary skill in the art would have been motivated to employ a cationic stabilizer in the composition. Possessing the cited prior art, one of ordinary skill in the art would have been motivated to employ BZ or CP to minimize the microbial content in the composition, thereby slow down the degradation and extends its stability.
Response to Arguments
Applicant's arguments filed 2/17/2026 with regard to the lyophilization and the water content of the composition have been fully considered but they are not persuasive. Applicant further argues that the pharmaceutical industry has largely abandoned the historical philosophy that “the dryer, the better” for lyophilized products, particularly for larger biopharmaceutical molecules, have been considered, but are not found persuasive. The examiner notes that bendamustine, even complexing with the cyclodextrin, is not considered big enough to be a macromolecule. Macromolecules like the biologicals are 10-100-fold bigger than small molecules like bendamustine. It is also known that bendamustine is degraded in alkaline environment, therefore, adding more water would accelerate the hydrolysis process to degrade the compound. Possessing the teachings of the cited prior art, one of ordinary skill in the art would therefore, minimize the residual water content to minimize the degradation of bendamustine. Therefore, the alleged unexpected benefits of stability achieved by minimizing the residual water content is considered as an expected result.
Applicant’s arguments filed 2/17/2026 averring the cited prior art’s failure to teach the addition of benzethonium and cetylpyridinum to the formulation of bendamustine, have been considered, but are not found persuasive. Although bendamustine is a bacteriostatic, preservative is generally not only used to prevent the growth of bacteria. Preservative is also anti-fungal since it is considered as anti-microbial agent. Therefore, adding the preservative into the bendamustine composition would still be appropriate.
Allowable Subject Matter
Claim 11 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
THIS ACTION IS MADE FINAL. 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 SAN MING R HUI whose telephone number is (571)272-0626. The examiner can normally be reached Mon - Fri 9:30-5:30.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
/SAN MING R HUI/Primary Examiner, Art Unit 1627
Prosecution Insights