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 .1
Status of Claims
Claims 1-11 are pending. Claims 1-5, 7, and 9-11 are examined. Claims 6 and 8 are withdrawn. galunisertib
Election/Restrictions
Applicant's election with traverse of the species in the reply filed on April 20, 2026 is acknowledged. The elected species are gemcitabine and galunisertib, reading on claims 5 and 10-11 specifically, and generically claims 1-4, 7 and 9. The traversal is on the ground(s) that claimed species do relate to a single general inventive concept of treating pancreatic cancer. This is not found persuasive because of the reasons stated in the species election requirement dated February 20, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Claim(s) 6 and 8 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on Apr 20 2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Interpretation and Additional Background Art
Claim(s) 1 and those dependent are directed to a method of treating pancreatic cancer (such as pancreatic ductal adenocarcinoma (PDAC) per claim 2) in a subject, with a known autotaxin inhibitor compound of formula I, Cambritaxestat2, (as a composition comprising a pharmaceutically acceptable diluent/carrier/excipient administered orally, per claim 3) in combination with other chemotherapeutic agents, such as gemcitabine and TGF-ß pathway inhibitor galunisertib (per claims 4-5, 7, 9-11).
WO 2022 207648 A1 while not cited as prior art, is noted where it discloses a compound of formula I, in combination with a PI3K delta inhibitor to treat pancreatic cancer.
Claim Objections
Claim 3 is objected to because of the following informalities:
In line 3, claim 3 recites “a pharmaceutically acceptable salt. . . . “ Claim 3 depends from claim 1, which established the antecedent basis for “pharmaceutically acceptable salt.” Therefore, the subsequent appearance of “pharmaceutically acceptable salt” in line 3 must be preceded by “the” or “said” instead of “a.” Amendment of claim 3 will overcome this objection. Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-5 and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 10,654,846 B2 (846 patent), issued May 19 2020. The ‘846 patent is cited on the PTO-892 form.
Regarding claims 1 and 3, the 846 patent teaches the claimed compound of formula I, aka Cambritaxestat
PNG
media_image1.png
328
302
media_image1.png
Greyscale
as well as a pharmaceutical composition comprising a pharm. acceptable diluent or carrier. See claims 1-2. The 846 patent compounds are known as autotaxin (ATX) inhibitors. See abstract. The 846 patent teaches that ATX is widely expressed in the pancreas of subjects. See column 1, lines 51-52. The 846 patent teaches “proliferative disorder[s]” are known to be unwanted/uncontrolled cellular growth, i.e. neoplastic (cancerous) growth, which can be treated including those cells of the pancreas. See column 46, lines 45-48.
While there is no specific working example from the 846 patent of Cambritaxestat treating pancreatic cancer, it teaches the genus of patients, i.e. those suffering from pancreatic proliferative disorder (i.e., pancreatic cancer), see column 1, lines 51-52 and column 46, lines 45-48; where the 846 patent specifically points to the claimed compound, Cambritaxestat. See claim 1.
Per MPEP 2131.02 III.3 (Genus-Species Situation), a generic disclosure (genus of cancer patients) will anticipate a claimed species covered by that disclosure, where the species can be “at once” envisaged by a person having ordinary skill in the art (PHOSITA) from the disclosure. As detailed above, the 846 patent points to the species of a pancreatic cancer patient at column 1 and column 46 that is readily envisaged from the genus teachings, to be treated with the species compound, Cambritaxestat.
Regarding claim 4-5 and 7, the 846 patent teaches administration of one or more additional chemotherapeutic agents (see column 48, lines 37-60) , including the elected species gemcitabine (column 48, line 49).
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.
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 1-5, 7 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over US 10,654,846 B2 (846 patent), in view of Hussain et al. Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression Cellular Oncology (2021) 44:673–687, published online Mar 10 2021. Hussain is cited on the PTO-892 form.
As required by Claim(s) 1, 3-5 and 7, the 846 patent teaches the claimed compound of formula I, aka Cambritaxestat
PNG
media_image1.png
328
302
media_image1.png
Greyscale
as well as a pharmaceutical composition comprising a pharm. acceptable diluent or carrier. See claims 1-2. The compounds of the 846 patent are known autotaxin (ATX) inhibitors. See abstract. The 846 patent teaches that ATX is widely expressed in the pancreas of subjects, see section titled ATX and cancer. See column 1, lines 51-52. The 846 patent teaches “proliferative disorder[s]” are known to be unwanted/uncontrolled cellular growth, i.e. neoplastic (cancerous) growth, which can be treated including those cells of the pancreas. See column 46, lines 45-48.
The 846 patent teaches the genus of patients, i.e. those suffering from pancreatic proliferative disorder (i.e., pancreatic cancer), see column 1, lines 51-52 and column 46, lines 45-48; where the 846 patent specifically points to the claimed compound, Cambritaxestat to treat them. See claim 1.
Regarding claim 4-5 and 7, the 846 patent teaches administration of one or more additional chemotherapeutic agents (see column 48, lines 37-60) , including the elected species gemcitabine (column 48, line 49).
It is noted that the 846 patent does not teach the species of treating the species of pancreatic ductal adenocarcinoma progress (PDAC) and administration of TGF-beta galunisertib, of claims 1-5, 7 and 9-11, where such species is spell out in claims 2 (PDAC as pancreatic cancer) and claims 7 and 9-11 (total of two additional chemotherapeutic agents, specifically, where the second chemotherapeutic agent is the TGF-beta inhibitor, galunisertib).
Per claims 2, 7 and 9-11, Hussain teaches suggests the treatment of the species of pancreatic cancer, PDAC, with a combination of gemcitabine and galunisertib so as to decrease metastases. See Results section of Abstract.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the 846 patent to treat pancreatic cancer patients with claimed compound, Cambritaxestat, with or without gemcitabine, as well as treat the species of PDAC, based on the teachings of Hussain, with a further second chemotherapeutic agent, the TGF-beta inhibitor, galunisertib (e.g. MPEP 2143 (a) combining prior art elements (treating pancreatic cancer (PDAC) with Cambritaxestat with gemcitabine and/or galunisertib) according to known methods to yield predictable results).
The PHOSITA would have had a reasonable expectation of success because per MPEP 2144.06 I.4, it prima facie obvious to combine equivalents known for the same purpose, i.e. combining Cambritaxestat with gemcitabine and/or galunisertib, to treat pancreatic cancer, including the species, PDAC as claimed.
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 1-5, 7 and 9-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 10654846B2 (846 patent) in view of US 20180016274 A1 (US Pub 274) and of Hussain et al. Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression Cellular Oncology (2021) 44:673–687, published online Mar 10 2021. The cited prior art are noted on the PTO-892 form.
It is noted that as required by Claim(s) 1, 3-5 and 7, the 846 patent teaches the claimed compound of formula I, Cambritaxestat as well as a pharmaceutical composition comprising a pharm. acceptable diluent or carrier. See conflict claims 1-2.
It is noted that conflict claims of the 846 patent do not teach the treatment of pancreatic cancer or various species of the claims 1, 3-5 and 7 with regard to the treatment of pancreatic cancer and combinations with gemcitabine as chemotherapy. Nor does it teach the aspect of species of 2 and 9-11 with regard to treatment of the pancreatic cancer species, PDAC further in combination with TGF-beta with galunisertib.
However, these deficiencies are corrected by the teachings of US Pub 274 (the corresponding pre-grant publication of the 864 patent) and Hussain.
The compounds of US Pub 274 are known autotaxin (ATX) inhibitors. See abstract. US Pub 274 teaches that ATX is widely expressed in pancreas of subjects, in the section titled ATX and cancer. See paragraph 5. US Pub 274 teaches “proliferative disorder[s]” are known to be unwanted/uncontrolled cellular growth, i.e. neoplastic (cancerous) growth, which can be treated including those of the pancreas. See paragraph 794.
US Pub 274 teaches the genus of patients, i.e. those suffering from pancreatic proliferative disorder (i.e., pancreatic cancer), see paragraphs 5 and 794; where US Pub 274 specifically points to the claimed compound, Cambritaxestat. See claim 1.
Regarding claim 4-5 and 7, US Pub 274 teaches administration of one or more additional chemotherapeutic agents, including the elected species gemcitabine (see paragraph 813).
It is noted that US Pub 274 does not teach the species of treating the species of pancreatic ductal adenocarcinoma progress (PDAC) and administration of TGF-beta galunisertib, of claims 1-5, 7 and 9-11, where such species is spell out in claim 2 (PDAC as pancreatic cancer) and claims 7 and 9-11 (total of two additional chemotherapeutic agents, such as TGF-beta inhibitor galunisertib).
Hussain teaches suggests the treatment of the species of pancreatic cancer, PDAC, with a combination of gemcitabine and galunisertib so as to decrease metastases. See Results section of Abstract.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the 846 patent, in view of its pre-grant publication, US Pub 274, to treat pancreatic cancer patients with claimed compound, Cambritaxestat, with or without gemcitabine, as well as treat the species of PDAC. Further, based on the teachings of Hussain, it would be obvious to combine with a further chemotherapeutic, the TGF-beta inhibitor, galunisertib. (e.g. MPEP 2143 (a) combining prior art elements (treating pancreatic cancer (PDAC) with Cambritaxestat with gemcitabine and/or galunisertib) according to known methods to yield predictable results).
The PHOSITA would have had a reasonable expectation of success because per MPEP 2144.06 I.5, it prima facie obvious to combine equivalents known for the same purpose, i.e. combining Cambritaxestat with gemcitabine and/or galunisertib, to treat pancreatic cancer, including the species, PDAC as claimed.
Claims 1-5, 7 and 9-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-4 of copending Application No. 18553333 (333 application) in view of US 20180016274 A1 (US Pub 274) and Hussain et al. Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression Cellular Oncology (2021) 44:673–687, published online Mar 10 2021.
US Pub 274 and Hussain are listed on the PTO-892 form.
Conflict claims 1-4 of the ‘333 application disclose a method of treating pancreatic cancer with Cambritaxestat and a PI3K inhibitor as well as a pharmaceutical composition(s) comprising a pharm. acceptable diluent or carrier. Conflict claims 7, 8 and 12 teach combinations with chemotherapy, gemcitabine, and treatment of PDAC as a species. While the conflict claims recite a PI3K inhibitor, they still read upon the claimed method as examined recites the transition phrase “comprising” with regard to the administered compounds.
The conflict claims do not teach the aspect of species of claims 9-11 with regard to treatment of the pancreatic cancer in combination with the TGF-beta with galunisertib. However, this deficiency is cured by Hussain as detailed below.
Hussain teaches suggests the treatment of the species of pancreatic cancer, PDAC, with a combination of gemcitabine and galunisertib so as to decrease metastases See Results section of Abstract.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the conflict application, to treat pancreatic cancer patients with claimed compound, Cambritaxestat, with or without gemcitabine, as well as treat the species of PDAC. Furthermore, based on the teachings of Hussain, with a further chemotherapeutic, the TGF-beta inhibitor, galunisertib (e.g. MPEP 2143 (a) combining prior art elements (treating pancreatic cancer (PDAC) with Cambritaxestat with gemcitabine and/or galunisertib) according to known methods to yield predictable results).
The PHOSITA would have had a reasonable expectation of success because per MPEP 2144.06 I.6, it prima facie obvious to combine equivalents known for the same purpose, i.e. combining Cambritaxestat with gemcitabine and/or galunisertib, to treat pancreatic cancer, including the species, PDAC as claimed. This is a provisional nonstatutory double patenting rejection.
Conclusion and Correspondence
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. 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.
/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a 371 of PCT/EP22/65562 06/08/2022
FOREIGN APPLICATIONS
UNITED KINGDOM 2108245.8 06/09/2021
2 CAS Registry Number: 1979939-16-6
N-[(1S)-1-(4-Chlorophenyl)ethyl]-3-[[4-(trifluoromethoxy)phenyl]methyl]-3H-imidazo[4,5-b]pyridine-2-propanamide (ACI)
Cambritaxestat
IOA 289
3 “[W]hether a generic disclosure necessarily anticipates everything within the genus … depends on the factual aspects of the specific disclosure and the particular products at issue.” Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1083, 89 USPQ2d 1370, 1375 (Fed. Cir. 2008). See also Osram Sylvania Inc. v. American Induction Tech. Inc., 701 F.3d 698, 706, 105 USPQ2d 1368, 1374 (Fed. Cir. 2012) (“how one of ordinary skill in the art would understand the relative size of a genus or species in a particular technology is of critical importance”).
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.” Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)).
4 "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
5 "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
6 "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
Prosecution Insights