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 National Stage entry of PCT/JP2021/012922, filed 03/26/2021, and claims foreign priority to JP2020-057561, filed 03/27/2020.
Information Disclosure Statement
The IDS’s filed on 12/10/2025, 7/29/2024, 6/3/2024, 2/29/2024 and 12/29/2022 have been considered. See the attached PTO 1449 form.
Election/Restrictions
Applicant’s election of cetuximab as the conjugate of a substance, saporin as the cytotoxin and the subject matter of claim 9 for when the conjugate and the like come into contact with the tumor cells, in the reply filed on 10/9/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon further search and consideration, the examiner has expanded the election of species and rejoined the subject matter of claim 19 and 29 for when the conjugate and the like come into contact with the tumor cells, since the prior art being relied upon teaches the subject matter of claim 19 and 29 for when the conjugate and the like come into contact with the tumor cells and the search is coextensive.
Claims 17-18, 27-28 and 37-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims Status
Receipt of Remarks filed on 10/9/2025 is acknowledged. Claims 9-38 are currently pending. Claims 17-18, 27-28 and 37-38 have been withdrawn. Accordingly, claims 9-16, 19-26, 29-36 are currently under examination.
Claim Objections
Claims 12, 22 and 32 are objected to because of the following informalities:
In claims 12, 22, and 32, the recitation “ERBB1”, “ERBB2”, “ERBB3” and “ERBB4” should not be abbreviated and should be spelled entirely the first time it is used in the claims.
Appropriate correction is required.
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 12, 15, 16, 22, 25, 26, 32, 35, 36 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 12, 22 and 32 recite the broad recitation “Epidermal Growth Factor Receptor”, and the claims also recite “ERBB1, ERBB2, ERBB4, or ERBB4” in parenthesis which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 15 recites the limitation "the medicament comprises Talaporfin Sodium". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 9 and claim 9 does not recite “medicament” and it is unclear which component of the previous claim the recitation “medicament” is referring to.
Similarly, claim 25 also recites the limitation "the medicament comprises Talaporfin Sodium". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 19 and claim 19 does not recite “medicament” and it is unclear which component of the previous claim the recitation “medicament” is referring to.
Similarly, claim 35 also recites the limitation "the medicament comprises Talaporfin Sodium". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 29 and claim 29 does not recite “medicament” and it is unclear which component of the previous claim the recitation “medicament” is referring to.
Claim 16 recites the limitation "the anti-EGFR antibody is Cetuximab". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 9 and claim 9 does not recite “anti-EGFR antibody” and it is unclear which component of the previous claim the recitation “the anti-EGFR antibody” is referring to.
Claim 26 also recites the limitation "the anti-EGFR antibody is Cetuximab". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 19 and claim 19 does not recite “anti-EGFR antibody” and it is unclear which component of the previous claim the recitation “the anti-EGFR antibody” is referring to.
Claim 36 also recites the limitation "the anti-EGFR antibody is Cetuximab". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 29 and claim 29 does not recite “anti-EGFR antibody” and it is unclear which component of the previous claim the recitation “the anti-EGFR antibody” is referring to.
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.
Claims 9-16, 19-26, 29-36 are rejected under 35 U.S.C. 103 as being unpatentable over Yip et al. (Molecular Pharmaceutics, Vol. 4, No. 2, 2006)(cited in IDS) in view of Baskaran et al. (Biomater. Res. Vol. 22, art. no. 25, 2018)(cited in IDS) and Doronina et al. (US 8,288,352 B2; Oct. 16, 2012).
Yip throughout the reference teaches Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization (PCI) in EGFR positive cancer cells.
Regarding claims 9, 19, 29, Yip teaches a method for killing tumor cells by targeting EGFR expressing cancer cells (tumor cells) with the model immunotoxin cetuximab-saporin using PCI (photochemical internalization) as a drug delivery method. This reads on allowing a conjugate of a substance (cetuximab) and a cytotoxin (saporin) to come into contact with the tumor cells. PCI is based on the principle of photodynamic therapy (PDT), which is approved for different cancers. PCI technology is based on the activation by light of photosensitizers. Specifically, Yip teaches the therapeutically approved cetuximab, which is a chimeric humanized murine mAb recognizing the epidermal growth factor receptor (EGFR), was linked to the type I ribosome-inactivating protein saporin. PCI of cetuximab saporin was established as a proof-of-concept in three different EGFR-positive human cancer cell lines (colorectal, HCT-116; prostate, DU-145; and epidermis, A-431). The cetuximab-saporin binds specifically to EGFR-positive cells. Yip specifically teaches HCT-116, DU-145, A-431 cells were incubated with TPPS2a (photosensitizer) for PDT only or, for the PCI experiments, coincubated with increasing concentrations of cetuximab-saporin. Cells were subsequently exposed to increasing doses of LumiSource light. This PCI protocol is referred to as “light after” PCI. Illuminations of cells were performed by using LumiSource. Yip teaches that PDT is dependent on three components, all of which are crucial to accomplish successful therapeutic outcome: (1) Light of wavelengths that correspond to the absorption properties of a (2) photosensitizer (PS). After light activation, the PS (photosensitizer) utilizes the absorbed energy in (3) oxygen dependent reactions to form reactive oxygen species (ROS). Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm. Thus, Yip teaches irradiating the tumor cells with a wavelength as the third/last step which reads on the third/last step recited in claims 9, 19, 29. Yip concludes that PCI of the immunotoxin cetuximab-saporin was demonstrated to be an effective and specific anti-cancer cell therapy and Yip proposes that PCI concept introduces a unique triple cytotoxicity with 1) cetuximab, 2) PDT, and 3) saporin. Photosensitizer for PDT employs TPPS2a. (see e.g., Abstract; Introduction; Experimental Section; Results and Discussion; Conclusion; Entire document).
Regarding claims 10, 11, 15, 16, 20, 21, 25, 26, 30, 31, 35, 36, as discussed supra, Yip teaches cetuximab in combination with saporin, which read on these claims.
Regarding claims 12, 22, 32, as discussed supra, Yip teaches a method for killing tumor cells by targeting EGFR expressing cancer cells (tumor cells).
Regarding claims 13, 23, 33, as discussed supra, Yip teaches three different EGFR-positive human cancer cell lines (colorectal, HCT-116; prostate, DU-145; and epidermis, A-431).
Regarding claims 14, 24, 34, as discussed supra, Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm.
(see e.g., Abstract; Introduction; Experimental Section; Results and Discussion; Conclusion; Entire document).
The teachings of Yip et al. have been set forth above. As discussed supra, Yip teaches photosensitizer for PDT employs TPPS2a, which is used in combination with cetuximab and saporin. Yip does not teach Talaporfin sodium, Porfimer sodium or Verteporfin in combination with cetuximab and saporin as required in the instant claims. As such, Yip also does not teach the wavelength effective for activating these agents. However, Baskaran cures these deficiencies.
Baskaran throughout the reference teaches clinical development of photodynamic agents and therapeutic applications. Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Baskaran discloses that second generation photosensitizers such as Visudyne (verteporfin), Photofrin (Porfimer sodium) and Laserphyrin (Talaporfin sodium) have been approved clinically and induce tumor regressions. Baskaran teaches Laserphyrin (Talaporfin sodium) is irradiated superficially with laser at wavelength of 664 nm and Photofrin (porfimer sodium) at wavelength of 630 nm. (see e.g., Abstract; Table 1; Laserphyrin section; Photofin section; Entire document).
Yip et al. does not expressly teach the order of when the conjugate (cetuximab) and cytotoxin (saporin) combination and the photosensitizer come into contact with the tumor cells. However, Doronina cures this deficiency.
Doronina teaches antibody drug conjugate (cetuximab) to kill/inhibit tumor cells in the treatment of cancer which include administering antibody drug conjugate and a chemotherapeutic agent such verteporfin. The conjugate drug can be administered concurrently with the chemotherapeutic agent or the chemotherapeutic agent can be administered prior or subsequent to administration of a conjugate drug. (see e.g., abstract; background section; claims; col. 56-58; entire document). This reads on the order of steps recited in claims 9, 19 and 29.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of Yip, Baskaran and Doronina and include Talaporfin sodium, Porfimer sodium or Verteporfin in combination with cetuximab and saporin instead of TPPS2a in the method of Yip as taught by Baskaran. Baskaran discloses that second generation photosensitizers such as Visudyne (verteporfin), Photofrin (Porfimer sodium) and Laserphyrin (Talaporfin sodium) have been approved clinically and induce tumor regressions. As such, the PDT inducing photosensitizer (e.g., verteporfin, talaporfin and porfimer) are photosensitizers commonly used in the art, and thus, one skilled in the art would have been motivated to replace TPPS2a of Yip with the photosensitizers taught by Baskaran. Further, regarding the wavelength effective for activation, Baskaran teaches Laserphyrin (Talaporfin sodium) is irradiated superficially with laser at wavelength of 664 nm and Photofrin (porfimer sodium) at wavelength of 630 nm. Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm. Thus, it would have been obvious to one skilled in the art to determine and optimize the wavelength needed for effective activation of the photosensitizers.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of Yip, Baskaran and Doronina and determine the order of when the conjugate (cetuximab) and cytotoxin (saporin) combination and the photosensitizer come into contact with the tumor cells. As discussed supra, Doronina teaches antibody drug conjugate (cetuximab) to kill/inhibit tumor cells in the treatment of cancer which include administering antibody drug conjugate and a chemotherapeutic agent such verteporfin. The conjugate drug can be administered concurrently with the chemotherapeutic agent or the chemotherapeutic agent can be administered prior or subsequent to administration of a conjugate drug. Thus, absence any evidence of unexpected effect, it would have been obvious to one skilled in the art to allow the photosensitizers (e.g. talaporfin) to come into contact with the tumor cells concurrently, prior to, or after cetuximab and saporin come into contact with the tumor cells. Changes in size, shape, or sequence of adding ingredients generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. See: MPEP 2144.04.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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 9-16, 19-26, 29-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 7-8, 11-12 of copending Application No. 17/916,642 (US20230149555A1) in view of Yip et al. (Molecular Pharmaceutics, Vol. 4, No. 2, 2006)(cited in IDS), Baskaran et al. (Biomater. Res. Vol. 22, art. no. 25, 2018)(cited in IDS) and Doronina et al. (US 8,288,352 B2; Oct. 16, 2012).
‘642 teaches a medicament and a method for killing tumor cells comprising allowing a conjugate of a substance that binds to a target substance on the surface of tumor cells and a cytotoxin to come into contact with the tumor cells, allowing a photosensitizing dye which Talaporfin sodium or Porfimer sodium to come into contact with the tumor cells, and irradiating the tumor cells with a wavelength effective for activating the photosensitizing dye to kill the cells. Claim 12 of ‘642 teaches allowing the conjugate, cytotoxin and photosensitizer to contact tumor cell at same time then irradiating the tumor cells. The cytotoxin is saporin and the conjugate of a substance is an antibody, an antibody, fragment, a ligand or a peptide. The tumor cells express EGFR, wherein the tumor cells are cancer cells of head and neck cancer, lung cancer and other cancers which are recited in instant claims.
‘642 does not expressly teach the antibody (conjugate substance) is cetuximab, the wavelength is 650 nm and the order of administration recited in claim 29. However, Yip, Baskaran and Doronina cure these deficiencies.
The teachings of Yip, Baskaran and Doronina set forth above are incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of ‘642 with Yip, Baskaran and Doronina and include cetuximab as the antibody because Yip also teaches a medicament and method of killing tumor cells wherein the conjugate drug is an antibody and specifically cetuximab is used in combination with saporin. It would have been obvious to use the antibody such as cetuximab because it is also taught to be useful in treating or killing tumor cells. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
Further, regarding the wavelength effective for activation, Baskaran teaches Laserphyrin (Talaporfin sodium) is irradiated superficially with laser at wavelength of 664 nm and Photofrin (porfimer sodium) at wavelength of 630 nm. Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm. Thus, it would have been obvious to one skilled in the art to determine and optimize the wavelength needed for effective activation of the photosensitizers.
As discussed supra, Doronina teaches antibody drug conjugate (cetuximab) to kill/inhibit tumor cells in the treatment of cancer which include administering antibody drug conjugate and a chemotherapeutic agent such verteporfin. The conjugate drug can be administered concurrently with the chemotherapeutic agent or the chemotherapeutic agent can be administered prior or subsequent to administration of a conjugate drug. Thus, absence any evidence of unexpected effect, it would have been obvious to one skilled in the art to allow the photosensitizers (e.g. talaporfin) to come into contact with the tumor cells concurrently, prior to, or after cetuximab and saporin come into contact with the tumor cells. Changes in size, shape, or sequence of adding ingredients generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. See: MPEP 2144.04.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Claims 9-16, 19-26, 29-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 18/694,587 (US20240316203A1) in view of Yip et al. (Molecular Pharmaceutics, Vol. 4, No. 2, 2006)(cited in IDS) and Baskaran et al. (Biomater. Res. Vol. 22, art. no. 25, 2018)(cited in IDS).
‘587 teaches a medicament for killing tumor cells comprising a conjugate of a substance that binds to a target substance on the surface tumor cells and a cytotoxin, and a glycosylated chlorin. The conjugate of a substance is an antibody. The cytotoxin is saporin. The tumor cells are cells that express EGFR and the tumor cells are cancers of head and neck cancer, lung cancer, etc. The medicament kills tumor cells by performing the step of allowing conjugate to come into contact with tumor cells, allowing glycosylated chlorin to come into contact with the tumor cells and irradiating tumor cells with a wavelength effective for activating the glycosylated chlorin. Claims 7-8 teach different timing/order of when conjugate come into contact with tumor cells which read on instant claims. The wavelength effective for activating the glycosylate chlorin is 600 to 800 nm.
‘587 does not expressly teach the antibody (conjugate substance) is cetuximab and the photosensitizer is talaporfin, porfimer or verteporfin. However, Yip and Baskaran cure these deficiencies.
The teachings of Yip and Baskaran set forth above are incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of ‘642 with Yip and Baskaran and include cetuximab as the antibody because Yip also teaches a medicament and method of killing tumor cells wherein the conjugate drug is an antibody and specifically cetuximab is used in combination with saporin. It would have been obvious to use the antibody such as cetuximab because it is also taught to be useful in treating or killing tumor cells.
Further, Baskaran discloses that second generation photosensitizers such as Visudyne (verteporfin), Photofrin (Porfimer sodium) and Laserphyrin (Talaporfin sodium) have been approved clinically and induce tumor regressions. As such, the PDT inducing photosensitizer (e.g., verteporfin, talaporfin and porfimer) are photosensitizers commonly used in the art, and thus, one skilled in the art would have been motivated to use the photosensitizers taught by Baskaran.
As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Claims 9-16, 19-26, 29-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/694,632 (US20250000998A1) in view of Yip et al. (Molecular Pharmaceutics, Vol. 4, No. 2, 2006)(cited in IDS), Baskaran et al. (Biomater. Res. Vol. 22, art. no. 25, 2018)(cited in IDS) and Doronina et al. (US 8,288,352 B2; Oct. 16, 2012).
‘632 teaches a medicament for killing tumor cells comprising a conjugate of a substance that binds to a target substance on the surface of tumor cells and a cytotoxin, and talaporfin sodium, porfimer sodium or verteporfin, wherein talaporfin sodium, porfimer sodium or verteporfin is administered after administration of the conjugate of a substance and a cytotoxin, and a wavelength effective for activating talaporfin, porfimer or verteporfin is irradiated after administration of talaporfin, porfimer or verteporfin. The conjugate of a substance is an antibody and cytotoxin is saporin. The tumor cells express EGFR, wherein the tumor cells are cancer cells of head and neck cancer, lung cancer and other cancers which are recited in instant claims. The wavelength effective for activating talaporfin, porfimer or verteporfin is 600 to 800 nm.
‘632 does not expressly teach the antibody (conjugate substance) is cetuximab, the wavelength is specifically 650 nm and the order of administration recited in claims 19 and 29. However, Yip, Baskaran and Doronina cure these deficiencies.
The teachings of Yip, Baskaran and Doronina set forth above are incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of ‘632 with Yip, Baskaran and Doronina and include cetuximab as the antibody because Yip also teaches a medicament and method of killing tumor cells wherein the conjugate drug is an antibody and specifically cetuximab is used in combination with saporin. It would have been obvious to use the antibody such as cetuximab because it is also taught to be useful in treating or killing tumor cells. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
Further, regarding the wavelength effective for activation, Baskaran teaches Laserphyrin (Talaporfin sodium) is irradiated superficially with laser at wavelength of 664 nm and Photofrin (porfimer sodium) at wavelength of 630 nm. Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm. Thus, it would have been obvious to one skilled in the art to determine and optimize the wavelength needed for effective activation of the photosensitizers.
As discussed supra, Doronina teaches antibody drug conjugate (cetuximab) to kill/inhibit tumor cells in the treatment of cancer which include administering antibody drug conjugate and a chemotherapeutic agent such verteporfin. The conjugate drug can be administered concurrently with the chemotherapeutic agent or the chemotherapeutic agent can be administered prior or subsequent to administration of a conjugate drug. Thus, absence any evidence of unexpected effect, it would have been obvious to one skilled in the art to allow the photosensitizers (e.g. talaporfin) to come into contact with the tumor cells concurrently, prior to, or after cetuximab and saporin come into contact with the tumor cells. Changes in size, shape, or sequence of adding ingredients generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. See: MPEP 2144.04.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Claims 9-16, 19-26, 29-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/012,050 (US20230242554A1) in view of Yip et al. (Molecular Pharmaceutics, Vol. 4, No. 2, 2006)(cited in IDS), Baskaran et al. (Biomater. Res. Vol. 22, art. no. 25, 2018)(cited in IDS) and Doronina et al. (US 8,288,352 B2; Oct. 16, 2012).
‘050 teaches a medicament for killing tumor cells and a method comprising allowing a compound of claim 1 and conjugate of a substance and a cytotoxin to come into contact with tumors cells, and allow killing the tumor cells by irradiating the cells with a wavelength that is effective for activating the compound. The conjugate of a substance is an antibody. The cytotoxin is saporin. The antibody is an antibody reacting against EGFR and the tumor cells are cancers of head and neck cancer, lung cancer, etc.
‘050 does not expressly teach the antibody (conjugate substance) is cetuximab and the photosensitizer which is talaporfin, porfimer or verteporfin, the wavelength is specifically 650 nm and the order of administration recited in instant claims. However, Yip, Baskaran and Doronina cure these deficiencies.
The teachings of Yip, Baskaran and Doronina set forth above are incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art to have combined the teachings of ‘050 with Yip, Baskaran and Doronina and include cetuximab as the antibody because Yip also teaches a medicament and method of killing tumor cells wherein the conjugate drug is an antibody and specifically cetuximab is used in combination with saporin. It would have been obvious to use the antibody such as cetuximab because it is also taught to be useful in treating or killing tumor cells.
Further, Baskaran discloses that second generation photosensitizers such as Visudyne (verteporfin), Photofrin (Porfimer sodium) and Laserphyrin (Talaporfin sodium) have been approved clinically and induce tumor regressions. As such, the PDT inducing photosensitizer (e.g., verteporfin, talaporfin and porfimer) are photosensitizers commonly used in the art, and thus, one skilled in the art would have been motivated to use the photosensitizers taught by Baskaran.
Further, regarding the wavelength effective for activation, Baskaran teaches Laserphyrin (Talaporfin sodium) is irradiated superficially with laser at wavelength of 664 nm and Photofrin (porfimer sodium) at wavelength of 630 nm. Yip teaches that efficient penetration of light requires wavelengths for photoactivation above about 600 nm and that the photosensitizer must be excited at wavelengths below about 850 nm. The therapeutic wavelength window is therefore usually defined as 600-800 nm. Thus, it would have been obvious to one skilled in the art to determine and optimize the wavelength needed for effective activation of the photosensitizers.
As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
As discussed supra, Doronina teaches antibody drug conjugate (cetuximab) to kill/inhibit tumor cells in the treatment of cancer which include administering antibody drug conjugate and a chemotherapeutic agent such verteporfin. The conjugate drug can be administered concurrently with the chemotherapeutic agent or the chemotherapeutic agent can be administered prior or subsequent to administration of a conjugate drug. Thus, absence any evidence of unexpected effect, it would have been obvious to one skilled in the art to allow the photosensitizers (e.g. talaporfin) to come into contact with the tumor cells concurrently, prior to, or after cetuximab and saporin come into contact with the tumor cells. Changes in size, shape, or sequence of adding ingredients generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. See: MPEP 2144.04.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/ALI S SAEED/Examiner, Art Unit 1616