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 .
Claim Status
Claims 1-18 and 20-21 are pending.
Claims 1, 2, 12 and 13 are examined herein.
Claims 3-11, 14-18 and 20-21 are withdrawn (see restriction/election below).
Priority
This application is filed 11/15/2021 and claims the benefit of domestic priority as below:
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Information Disclosure Statements
No IDS(s) received.
Election/Restrictions
Applicant elects Group I, claims 1, 2, 12 and 13, is drawn to products, without traverse in the reply field on 06/24/2026 is acknowledged. Claims 3-11, 14-18 and 20-21 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected process of making products, there being no allowable generic or linking claim.
The species of election was not required.
Accordingly, claims 1, 2, 12 and 13 will be examined on their merits.
Claim Objections
Claims 2, 12 and 13 objected to because of the following informalities:
Claim 2 is objected to because the phrase “"amorphous polymorphic form" is a scientific contradiction, as amorphous means a material lacks internal order, while polymorphism refers to a compound's ability to form multiple distinct crystal structures.
Claim 12 is objected to because the phrase “at least five” ordinarily means five and more. The additional of “or more” after “at least five” does not identity a different numerical requirement. For the clarification, the phrase should be “comprising at least five peaks selected from…”.
Claim 13 is objected to because a conjunction such as “and” or “or” is missed at the end of the peak.
Claim Rejections - 35 USC § 112
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.
The rejections under this section are made when the scope of the claimed subject matter is not clear. (See MPEP 2173)
Claim 13 is 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 13, the phrase "further comprising peaks at 2-theta angles selected from" without a conjunction renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Neither the claim nor the specification clearly states whether all of the listed peaks, some of the listed peaks, or only one of the listed peaks are required.
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.
Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zarzuelo Alba et al., (US 2023/0399344 A1, pub’d 12/14/2023, PCT filed 11/23/2020, EP Foreign Priority Date 11/21/2019, hereinafter “Alba”), in view of Chintalapati et al., (US 2024/0352039 A1, pub'd 10/24/2024, Foreign Priority Date 08/31/2021).
With respect to independent claim 1, the claim recites that a pure lurbinectedin compound of Formula-V having purity greater than 99.7% wherein content of one or more impurities selected from in-situ intermediate impurity E, Deacetyl impurity F and Dehydroxy impurity G is lower than 0.15%.
Alba teaches that 1) lurbinectedin in amorphous form A and analytical results for batches of purity lurbinectedin (paragraph [0015] and [0173]); 2) identifying methodologies that allow for complete dissolution of lurbinectedin in desired buffers whilst minimizing impurity generation (paragraph [0124]); and 3) lurbinectedin related impurities may include a deacetylation of lurbinectedin, degradation product (i.e., impurity G corresponding as the instant impurity G; and impurity B corresponding as the instant impurity F) and/or unspecified impurity (paragraph [0140], [0144] and [0154]-[0156])
Alba further teaches that batch P03 in table 1 (paragraph [0173]) as total impurities of approximately 0.3 area percent, and individual impurity peaks in the purified material at approximately 0.09 area percent (retention time (rrt) 0.72-0.76), 0.08 area percent (rrt 1.10-1.11, corresponding as the instant impurity G), 0.07 (rrt 1.12), and 0.09 (rrt 1.29-1.30), with other listed impurity peaks not detected. (paragraph [0175]). Batch P04 in table 1 (paragraph [0173]) as total impurities of approximately 0.2 area percent with 0.09 and 0.10 area percent of individual impurities. Thus, Alba teaches the a pure lurbinectedin compound having purity 99.7% wherein content of Dehydroxy impurity G is 0.08 %.
Alba fails to teach a pure lurbinectedin compound having purity greater than 99.7%.
Chintalapati teaches that 1) an improved and industrially visible process for preparing lurbinectedin and crystalline polymorph designated Form-N (paragraph [0001]); 2) preparing crude lurbinectedin purifying the crude product by flash chromatography, and subsequently subjecting the purified material to solvent concentration, co-distillation, cooling, filtration, and drying to obtain crystalline Form-N of lurbinectedin (paragraphs [0014]-[0017]); and 3) in example 3 that the resulting Form-N of lurbinectedin is obtained with a purity of 99.8%.
It would have been obvious to a PHOSITA at the time of the invention to use the preparation and purification teachings of Chintalapati to obtain high purity lurbinectedin for use in preparing the amorphous Form A taught by Alba. Both references concern the preparation, purification, isolation, and crystalline polymorph of the same active pharmaceutical lurbinectedin. Chintalapati shows that lurbinectedin having a purity of 99.9% can be obtained, while Alba teaches preparation of purified amorphous lurbinectedin having individual lurbinectedin related impurity (i.e., impurity G) levels below 0.15 area percent. Therefore, a person having ordinary skill in the art would have been motivated to use high purity lurbinectedin prepared with a reasonable expectation of obtaining amorphous lurbinectedin having a purity greater than 99.7% and low levels of the identified impurities.
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (D) in the independent claim 1, it would have been prima facie obvious to known preparation and purification techniques that provide lurbinectedin having a purity of 99.8% taught by Chintalapati, and purified amorphous lurbinectedin having individual lurbinectedin related impurity (i.e., impurity G) levels below 0.15 area percent taught by Alba. Applying Chintalapati’s purification teachings to the lurbinectedin used in purification techniques for their established purpose of improving chemical purity and reducing process related and degradation impurities.
With respect to claim 2, the claim recites that the pure Lurbinectedin of claim 1, wherein pure Lurbinectedin is amorphous polymorphic form of Lurbinectedin or RK-1 polymorphic form of Lurbinectedin of formula (V).
Alba teaches amorphous Form A lurbinectedin and confirms the amorphous character of the material by XRPD (paragraph [0172]).
Conclusion
Claims 1, 2 and 13 are rejected.
Claims 2, 12 and 13 objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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