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 1-6, 9-11, 16, 21, 23-28 are original. Claims 7, 13, and 17 are currently amended. Claims 8, 12, 14-15, 18-20, 22, and 29 are cancelled. Claims 1-7, 9-11, 13, 16-17, 21, and 23-28 are pending and under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in INDIA on February 10, 2024. It is noted, however, that applicant has NOT filed a certified copy of the IN02341053567 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed 07/12/2026 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Claim Objections
Claim 4, 17, 23, and 25-28 are objected to because of the following informalities:
Claim 4 says “polyethylene glycol is selected from PEG 200 or PEG 300 or PEG 400 or PEG 600 or PEG 900”. This is improper Markush group. Proper syntax is “polyethylene glycol is selected from PEG 200, PEG 300, PEG 400, PEG 600, or PEG 900”.
Claim 17 states “2-8 C”. Proper syntax is 2-8 °C.
Claim 23 states “less than 0.5% deacetyl impurity”. Proper syntax is “less than 0.5% of a deacetyl impurity”
Claims 25 to 28 recite “…mg/mL hydrochloric acid”. Proper syntax is “…mg/mL of hydrochloric acid”.
Claims 26 and 27 recite “. wherein the composition has a pH between 2.0 to 6.0”. Proper syntax is “, wherein the composition has a pH between 2.0 to 6.0”.
Claims 26 and 28 recites “…mg/mL ethanol”. Proper syntax is “…mg/mL of ethanol”.
Claims 27 and 28 recites “…mg/mL benzyl alcohol”. Proper syntax is “…mg/mL of benzyl alcohol”.
Appropriate correction is required.
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 the applicant regards as his invention.
Claims 6-7 and 21 and 23 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 6, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 7 is indefinite for being dependent on indefinite claim 6.
The term “stable” in claim 17 is a relative term which renders the claim indefinite. The term “stable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 21 recites “at least 98% of Lurbinectedin content”. However, the unit of percentage (e.g., w/w, v/v, w/v, molar %) is not specified.
Claims 21 and 23 respectively recite the “impurities” and “impurity” to be less than a certain percent. However, the unit of percentage (e.g., w/w, v/v, w/v, molar %) is not specified.
Claims 21 and 23 recite respectively recite the “impurities” and “impurity”, which is a broad and undefined term encompassing a wide variety of chemically distinct materials, each having different properties/effects on the composition. The claim and specifications fail to sufficiently provide any structural, functional, or compositional limitation that would define what constitutes an impurity or impurities to provide the metes and bounds of this genus. Therefore, the scope of this claim is unclear, and thus indefinite.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-7, 9-11, 13, 16, and 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Robbins (US20090325906A1) in view of Coffman (US20190374470A1) in further view of Calvo (US20230027502A1).
Robbins discloses methods, compositions, and kits for the use of blood-tissue barrier (BTB) transport protein modulators (e.g., ethanol) [¶4]. Robbins teaches that the composition may contain an active agent [¶484]. Robbins teaches that the composition may be in the form of an injection [¶636], and polyethylene glycol as lubricants [¶515]. Robbins teaches that the composition may include solubilizers such as PEG-400 and PEG-200 [¶577]. Robbins teaches that the composition may include hydroxypropyl-β-cyclodextrin as an oligosaccharide [¶9]. Robbins teaches that additional solubilizers such as ethanol and benzyl alcohol can be used in the composition [¶576]. Robbins teaches that the pH of the composition can be less than 6 [¶536].
However, Robbins does not explicitly define the concentrations of its active agent and excipients as defined in claim 1, nor does it teach the presence of lurbinectedin in such compositions.
Coffman teaches particles, compositions including the particles, and methods of making the particles using electrospray [¶abstract]. Coffman teaches that the composition may be administered via injectable routes such as intra-muscular, intra-arterial, and intra-vascular, and may overall improve the injectability of the agents [¶¶20, 37, 84, 86]. Coffman teaches that the therapeutic (i.e., active) agents of the composition may be within the range of 0.0001 to 1000 mg/mL [¶101]. Coffman further teaches that the composition may include additional excipients (i.e., “other components”) such as pH adjusting agents, polymers, polyethylene glycol, benzyl alcohol, carbohydrates, and organic solvents such as ethanol, with each at concentrations ranging from 0.0001 to 99% w/v (i.e., 0.001 to 990 mg/mL) [¶6].
Calvo teaches methods for the treatment of small cell lung cancer (i.e., “SCLC”) patients by administering therapeutic amounts of lurbinectedin by intravenous infusion [¶abstract]. Calvo teaches that lurbinectedin compositions may be in the form of solutions [¶86]. Calvo teaches that solutions of compositions containing lurbinectedin may be diluted to form an injection solution [¶95].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the injectable pharmaceutical compositions taught by Robbins by selecting the concentrations of the active ingredients and excipients according to Coffman and by selecting Lurbinectedin as the active agent as taught by Calvo. This is because Robbins teaches that PEG, cyclodextrins, ethanol, and/or benzyl alcohol, and pH adjusters are suitable components of injectable pharmaceutical compositions, while Coffman teaches that such components may be employed over concentration ranges encompassing the presently claimed ranges, and Calco meanwhile teaches lurbinectedin as an intravenously administered active agent in a solution suitable for dilution and injection. Furthermore, all three references require nothing more than the components in the present claims, which thus satisfies the closed “consisting of” limitations of claims 25-28 in addition to the exclusion limitations of claims 13 and 16. A person of ordinary skill in the art would have been motivated to make these selections to provide a solubilized, pharmaceutically acceptable injectable formulations of Lurbinectedin having suitable concentration and pH for intravenous injection, via using known injectable excipients for their established functions. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because all three references are directed to compatible components having known purposes for injection, with selection of their clamed concentrations thus being a matter of routine optimization of result-effective variables.
Claims 17, 21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Robbins (US20090325906A1) in view of Coffman (US20190374470A1) in further view of Calvo (US20230027502A1) in further view of Dubewar (US20220008337A1).
Robbins, Coffman, and Calvo collectively teach all the required limitations of claims 1-11, 13, 16, and 24-28.
However, Robbins, Coffman, and Calvo fail to collectively teach the required limitations of claims 17, 21, and 23.
Additionally, Calvo (as cited above) teaches a form of its compositional impurity to be a degradation product resulting from deacetylation of lurbinectedin [¶21].
Dubewar discloses injectable compositions solutions comprising meloxicam or its pharmaceutically acceptable salts [¶abstract]. Dubewar teaches that additional active agents and excipients may be added to the composition [¶¶29, 105]. Dubewar teaches that the composition may be stable when stored for at least 3 months at 2-8° C [¶197], with the level of impurity in the composition being not more than 0.5% when stored for 3, 6, 12, 18, 24, or 6 months when stored at a temperature of 2-8° C [¶205]. Dubewar notes that injectable dispersions are fundamentally unstable (paragraph 10). Dubewar, thus, seeks to make more stable formulations of its drug for injection (paragraphs 13-16). Dubewar does provide ready-to-dilute formulations (paragraphs 28-29).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to further modify the injectable lurbinectedin composition of Robbins, Coffman, and Calvo in view of Dubewar to provide an injectable formulation stable under refrigerated storage and having reduced impurity levels. This is because Dubewar teaches that injectable pharmaceutical compositions may be formulated to remain stable at 2-8° C for periods encompassing the presently claimed storage periods and to maintain total and individual impurity levels below the presently claimed thresholds as measured by HPLC. A person of ordinary skill in the art would have been motivated to optimize the known injectable Lurbinectedin composition for refrigerated shelf stability and reduced degradation in order to provide a commercially suitable pharmaceutical product. One of ordinary skill in the art would have had a reasonable expectation of success because Dubewar demonstrates that such stability and impurity control are achievable in injectable liquid pharmaceutical compositions of a drug using conventional formulation techniques.
Conclusions
No claim is found allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARYA AHMADI BAZARGANI whose telephone number is (571)272-0211. The examiner can normally be reached Monday - Friday 9:00AM - 5:00 PM.
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, Brian-Yong Kwon can be reached at (571) 272-0581. 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.
Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/Primary Examiner, Art Unit 1613
Prosecution Insights