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 .
Priority
This application is a 371 of PCT/IB2021/053096 (04/15/2021),
and claims foreign priority to ITALY 102020000008209 (04/17/2020).
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.
Claims 1-21 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.
Claim 1, step d, uses the language “the NaBr salt” which lacks an antecedent basis in the claims as it is unclear whether the claim is referring to the earlier salt recited in the claim or is referencing a different new salt. As a result, one of ordinary skill in the art would find the claim confusing and ambiguous such that the claim is rendered indefinite. Thus, the claim including those that depend therefrom, claims 1-21, are rejected as indefinite.
Claim 9 includes the language “preferable” which renders the claim indefinite (MPEP 2173.05(d)).
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.
Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Leonelli et al. (Helv. Chim. Acta. 2005, 88, 154-159) in view of Campisi et al. (US20110189265).
Regarding claim 1, Leonelli teaches preparation of HA-paclitaxel conjugate as shown in Scheme 2 (p. 156):
PNG
media_image1.png
386
663
media_image1.png
Greyscale
The experimental details of the preparation are provided on p. 158:
PNG
media_image2.png
449
651
media_image2.png
Greyscale
Thus, Leonelli teaches the claim’s step (a) activating paclitaxel in CH2Cl2 (organic solvent) with 4-bromobutanoic acid (aka 4-bromobutyric acid spacer/linker), with DMAP (catalyst) to obtain compound (6) (intermediate of the HA-paclitaxel conjugate). Leonelli teaches equivalents to claim’s step (b) with the intermediate being washed, dried, evaporated, column chromatograph (CC) and crystallized (“EtOH/hexane 1:1”) to give a “white solid”. Leonelli teaches equivalent to step d including washing with ethanol and water, dialysis against distilled water and freeze-drying.
Leonelli does not specifically teach the particular crystallizing step in step b, the use of DMSO in step c, and step d’s purifying steps.
Campisi teaches preparation of conjugates of HA with chemotherapeutic drugs, including HA-paclitaxel conjugates (Abstract). Campisi teaches synthesis of the HA-drug conjugates including combining the drug intermediate with HA TBA in DMSO ([0085]; [0093]-[0094]) followed by the addition of an NaBr solution and precipitation with ethanol, and washing with ethanol ([0086]-[0087]; [0095]; [0097]) followed by drying under vacuum at 40 C ([0087]; [0089]; [0095]).
One of ordinary skill in the art following the teaching of Leonelli would have readily considered combining the teachings with Campisi which is in the same field of endeavor of HA-drug conjugate preparations. One of ordinary skill in the would consider routine the modification of Leonelli’s preparation steps to optimize the purity and efficacy of the resulting HA-drug conjugate product, including using well-known steps of isolation/purification by crystallization as suggested by Leonelli in precipitation of solids as well as using known solvents and rearranging preparation/purification steps. One of ordinary skill in the art would have considered utilizing the solvent DMSO instead of Leonelli’s DMP in view of Campisi’s success with DMSO in the same step of preparing HA TBA salt. One of ordinary skill in the art would also have considered replacing Leonelli’s brine (NaCl) with Campisi’s NaBr in view of Campisi’s success with NaBr in the same/equivalent ion exchange/precipitation step. One of ordinary skill in the art would have also considered utilizing a similar workup as Campisi’s including filtration/washing with ethanol and drying at 40C both at atmospheric pressure and under vacuum which would be saturated initially in the process. One of ordinary skill in the art would have had a reasonable expectation of success in the modified combination due to the high level of skill in the art and the prior art being to the same type of HA-drug conjugate preparation.
Regarding claim 2, Leonelli teaches the carbodiimide is EDC.
Regarding claim 3, Leonelli teaches the catalyst is DMAP.
Regarding claim 3, Leonelli teaches the catalyst is DMAP.
Regarding claim 4, Leonelli teaches use of hexane as a solvent in the equivalent step b which is a homolog of heptane (differing by one repeating -CH2- group) such that one of ordinary skill in the art would expect similar effect and utilize such as solvent in the crystallization step (see MPEP 2144.09).
Regarding claim 5, sample workup steps including drying are routine in the art and one of ordinary skill in the art would know that time and temperature are results effective variables as Leonelli and Campisi varied time and temperature in their workups, such that one of ordinary skill in the art would optimize the same variables and arrive at the claimed invention through routine experimentation.
Regarding claim 6, Leonelli teaches the HA is ~ 185 kDa.
Regarding claims 7-8, specifying the origin of the HA, the claim does not recite this as a required step, but instead uses the language as a means of defining the structure of the product which is characterized by average molecular weight. As with claim 6, Leonelli teaches the HA is ~ 185 kDa. In addition, Campisi teaches the HA derivatization in the same range and is fermentative in origin ([0071]).
Regarding claim 9, the process of claims 1-8 are rendered obvious as detailed above and the product produced by the process steps is also rendered obvious. In addition, Campisi teaches similar levels of derivatization, fermentative origin, molecular weight, solid, and purity all of which one of ordinary skill in the art would consider in optimization of the resulting product to improve therapeutic efficacy and arrive at the claimed invention.
Regarding claim 10, the process of claims 1-8 are rendered obvious as detailed above and the product produced by the process steps is also rendered obvious. In addition, one of ordinary skill in the art would optimize purity of the resulting product to improve therapeutic efficacy and arrive at the claimed invention.
Regarding claim 11, Campisi teaches the HA derivatization in the same range ([0071]) which one of ordinary skill in the art would optimize through routine experimentation for therapeutic efficacy and arrive at the claimed invention (MPEP 2144.05).
Regarding claims 12-13, Leonelli suggests the use of the conjugate for treating ovarian cancer (p. 155) and Campisi teaches formulations including 5% glucose ([0078], [0100]-[0102], [0124], [0150], [0163]) which one of ordinary skill in the art would consider in optimization of the formulation and arrive at the claimed invention through routine experimentation.
Regarding claim 14, Leonelli teaches the use of EDC.
Regarding claim 15, Campisi teaches the HA derivatization in the same range ([0071]) which one of ordinary skill in the art would optimize through routine experimentation for therapeutic efficacy and arrive at the claimed invention (MPEP 2144.05).
Regarding claim 16, Leonelli teaches use of hexane as a solvent in the equivalent step b which is a homolog of heptane (differing by one repeating -CH2- group) such that one of ordinary skill in the art would expect similar effect and utilize such as solvent in the crystallization step (see MPEP 2144.09).
Regarding claim 17-19, sample workup steps including drying are routine in the art and one of ordinary skill in the art would know that time and temperature are results effective variables as Leonelli and Campisi varied time and temperature in their workups, such that one of ordinary skill in the art would optimize the same variables and arrive at the claimed invention through routine experimentation.
Regarding claim 20, Leonelli teaches the HA is ~ 185 kDa.
Regarding claims 21-22, Leonelli suggests the use of the conjugate for treating ovarian cancer (p. 155) and Campisi teaches formulations including 5% glucose ([0078], [0100]-[0102], [0124], [0150], [0163]) which one of ordinary skill in the art would consider in optimization of the formulation and arrive at the claimed invention through routine experimentation.
With each of the above claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art in the same field of endeavor. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed with a reasonable expectation of success.
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.
Claims 1-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9789200. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims are to a scope of HA-antitumoral compounds where the supporting disclosure includes antitumoral of HA-paclitaxel and as detailed in the 35 USC 103 rejection over Leonelli et al. (Helv. Chim. Acta. 2005, 88, 154-159) in view of Campisi et al. (US20110189265 – PGPUB of US9789200), and incorporated herein, renders the instant claims obvious for the same reasons.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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, Joseph McKane can be reached at 571-272-0699. 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.
/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626