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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/08/2026 has been entered.
Status of Claims
Claims 23 and 42 are amended. Claims 23-28, 30-44, and 67-69 are pending and under examination.
Response to Remarks filed 04/08/2025
The rejection of claims 23-28, 33-44, and 67-69 under 35 U.S.C. 112(b) has been withdrawn, because claim 23 has been amended to remove the recitation of the 2 mg/kg to 10 mg/kg dose range.
Applicant’s arguments with respect to the 35 USC 112b rejection of claim 42 has been fully considered and are persuasive. The amendment to claim 42 which deletes “TROP2 overexpressing cancer as” and inserts “TROP2-expression in” remedies the rejection. Therefore, the 35 USC 112b rejection of claim 42 is withdrawn.
Applicant’s arguments with respect to the 35 USC 103 rejection of claims 23-28 and 30-44, and 67-69 have been fully considered and are not persuasive.
Specifically, Applicant argues none of the cited references teach or suggest the subject matter of the amended claims. Specifically, there is no teaching or suggestion in Agatsuma or Shvartsur that would motivate a person of ordinary skill to provide an anti-TROP2 antibody-drug conjugate as currently defined in amended claim 1 for treating non-small cell lung cancer (NSCLC), breast cancer, or urothelial cancer by administration at a specific dose of 4 mg/kg or 6 mg/kg, once every 3 weeks or once every 4 weeks.
However, Agatsuma et al disclose use of the exact TROP-2 ADC in NSCLC, breast cancer, and urothelial cancer as discussed above. Additionally, the 35 USC 103 rejection of 04/09/2025 noted that where ranges would be arrived at through routine optimization, they are deemed obvious.
Applicant further argues the claimed method provides unexpected technical effects/advantages that could not have been predicted or appreciated based on Agatsuma or Shvartsur. Applicant presents exhibits 1-4 to support an argument that the method provided unexpected technical effects/advantages.
As Agatsuma et al discloses the use of the TROP-2 ADC in NSCLC, breast cancer and urothelial cancer at a dose of 3mg/kg, the exhibits are examined to assess any unexpected technical effects/advantages of the specific dose scheme of exhibits 1-4.
The dose merely presents an expected increased efficacy with increased dosage and increased toxicity with increased dosage. The choice of 6mg/kg when compared to 4mg/kg or 8mg/kg is obvious. It is well established in the field when establishing PD/PK for a drug, particularly in cancer, that the maximum tolerated dose will be established through routine optimization. Furthermore, the results are not unexpected as ORR was similar to those seen in other TROP2 ADC trials such as the IMMU-132-01 trial disclosed by Bardia et al prior to the earliest effective filing date of the instant application (Bardia et al, New England Journal of Medicine, vol 380, 8, 741-751, 2019). Bardia at al discloses an ORR of 33% (Bardia et al, pg. 741, Abstract). Therefore the 35 USC 103 rejection of claims 23-28 and 30-44, and 67-69 are maintained.
Applicant’s affidavit cites Exhibits 1-5. Exhibits 1-4 have been previously considered. Exhibit 5 has been fully considered and is not persuasive. Exhibit 5 discloses the same doses of 4, 6, and 8 mg/kg in Lung Cancer, Breast Cancer, and Urothelial Cancer that have previously been discussed. It is routine in the art to increase doses for effectiveness and to find a dose that balances efficacy with tolerance. Therefore, the 35 USC 103 rejection is maintained.
Applicant’s arguments with respect to the Double Patenting rejection have been fully considered and are not persuasive. Specifically, Applicants claims that the Double Patenting rejection is overcome by amendments to the claims and the reasons discussed in the 103 rejection. The instant claims are obvious in view of Agatsuma and Shvartsur. The arguments and exhibits are not convincing and merely represent obvious doses reached by routine optimization. Therefore, the Double Patenting rejections are maintained.
The Following Previously Presented Rejections are Maintained
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.
Claim(s) 23-28 and 30-44, and 67-69 are rejected under 35 U.S.C. 103 as being unpatentable over Agatsuma et al (US9850312, filed 06/20/2016) in view of Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
Regarding claims 23 and 26-27, Agatsuma et al disclose the method of using the pharmaceutical composition of a TROP2 ADC with identical CDR sequences and structure of the instant application to treat several types of cancer. Specifically, the antibody of Agatsuma et al discloses an antibody with 100% sequence identity and Succinimid-3-yl-N is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure on the nitrogen atom at position 1. (Agatsuma et al, Claims 1, 7, and 8).
Agatsuma et al discloses SEQ ID NO: 45 (including aa 1-121) and SEQ ID NO: 46 (including aa 1-109) of the instant application (Agatsuma et al, SEQ ID NO: 12, Figure 3 legend and SEQ ID NO: 18, Figure 6 legend 226) in the same antibody hTINA1-H1L1. As a heavy chain and light chain, this antibody combination is readily useable in the method of claim 23, leading to the predictable result of the instant application claims 26 and 27. That they are in the same antibody is clear from claim 9 of Agatsuma. This antibody was conjugated to the drug payload of instant claim 23 as shown in the figure spanning columns 117-118. This drug is ADC13 (column 118, paragraph 3) and so was clearly used at the doses above 3 mg/kg to treat pancreatic adenocarcinoma (Column 122, paragraph 3) and esophageal cancer (Column 122, paragraph 4) as well as Figures 25-27.
Agatsuma et al further discloses:
Composition and concentration of the pharmaceutical composition may vary depending on administration method. However, the anti-TROP2 antibody-drug conjugate contained in the pharmaceutical composition of the present invention can exhibit the pharmaceutical effect even at a small dosage when the antibody-drug conjugate has higher affinity for an antigen, that is, higher affinity (= lower Kd value) in terms of the dissociation constant (that is, Kd value) for the antigen. (Agatsuma et al, column 62, paragraph 3)
Regarding claim 28, Agatsuma et al. discloses the anti-TROP2 antibody of the ADC lacks a lysine residue at the carboxyl terminus of the heavy chain. (Agatsuma et al, claim 13). Therefore, it is obvious to remove the lysine from SEQ ID NO. 12 above to arrive at a still functional antibody variant of hTINA1. This is exchange of one predictably functional heavy chain for another.
Regarding claim 33, the method of claim 23 is addressed above. Furthermore, Agatsuma et al discloses that the ADC can be administered intravenously. (Agatsuma et al, column 61, paragraph 6, Column 122, paragraph 3 and Column 122, paragraph 4)
Regarding claim 35, Agatsuma et al discloses the method of use against pancreatic and esophageal cancer as discussed supra.
Regarding claim 41, PHOSITA immediately envisages the cancer targets of Agatsuma express the ADC target TROP2 and so it is an obvious target. This is also explained in Column 1, paragraph 4 as the antibody’s antigen is expressed on cancer cells.
Regarding claim 44, Agatsuma et al discloses the method of claim 23 can be administered as a pharmaceutical composition with additives (Agatsuma et al, column 61, paragraph 5). Said additives meet the limitation of pharmaceutically acceptable formulation component. Thus, compositions with the ADC above and acceptable additives are obvious here and standard practice in this art for therapeutic administration.
Regarding claim 36, Agatsuma does not teach use of the conjugate, their ADC 13 against NSCLC. However, Agatsuma et al discloses a method of use of a similar conjugate against TROP2+ Calu-3 cells (an NSCLC lung adenocarcinoma). (Agatsuma et al, Column 122, paragraph 5) and since they express the target of their ADC 13, it would have been obvious to use ADC 13 of Agatsuma against this cancer type also with a reasonable expectation of success in using the ADC to kill said cancer cells.
Agatsuma et al further discloses:
Thus, for determining dosage of the antibody- drug conjugate, the dosage can be determined in view of a situation relating to the affinity between the antibody-drug conjugate and antigen. When the antibody-drug conjugate of the present invention is administered to a human, for example, about 0.001 to 100 mg/kg can be administered once or administered several times with an interval of one time for 1 to180 days. (Agatsuma et al, column 62, paragraph 3)
Additionally, Agatsuma et al teaches the use of the antibody drug conjugate administered at doses of 3mg/kg as discussed above and similar ADC at 10mg/kg (Agatsuma et al, column 120, paragraph 4). It is clear from all these teachings, and as is known in the art, that ADC dose is a result effective variable. It determines the efficacy of a treatment.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
The claimed dose ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art. Regarding claims 30-32 therefore, the doses are result effective variables in the range taught by Agatsuma and so will be arrived at by routine experimentation.
Regarding claims 24 and 25, the method of claim 23 is addressed above. Agatsuma et al further discloses the average number of units per antibody is in a range of 2 to 8 (Agatsuma et al, claim 2). The claimed ranges of instant claims 24-25 merely represent an obvious variant and/or routine optimization of the values of the cited prior art. This is clear since the amount of anti-tumor compound conjugated to the antibody determines in part the anti-tumor efficacy of the ADC. More anti-tumor agent correlates generally with more anti-tumor effect. Thus, the ranges of claims 24-25 are result effective variables and will be arrived at by routine optimization by PHOSITA.
Regarding claim 34, Agatsuma teaches the drug can be administered more than once in a 3 month span. The interval of claim 34 will determine the concentration of antibody held in the patient’s body and thus the amount kept present to attack the cancer. Thus, it is a result effective variable and will be arrived at by routine experimentation.
Agatsuma et al does not disclose the use of the ADC of the instant application wherein cancer is resistant or refractory. Additionally, Agatsuma et al does not disclose that the ADC of the instant application is used against Trop-2 overexpressing cancers or an inoperable or recurrent cancer. It is noted that Trop-2 expression is implicit to the cancer targets of the instant application as the ADC will not work if the target is not present as discussed above.
Regarding claims 37, 38, 41 and 42 Shvartsur et al discloses that Trop2 overexpression is reported in ovarian cancer, a notably aggressive, treatment resistant cancer, and that 82% of chemotherapy resistant ovarian tumors express Trop2 (Shvartsur et al, pg. 96 Paragraph Q. Ovarian Cancer). Therefore, it would be obvious to combine the teachings of Shvartsur et al and Agatsuma et al to obtain claim 37, 38, 41, and 42 as resistance, refractory, and chemoresistance cancers like the ovarian cancers of Shvartsur have the target of the ADC of Agatsuma and so would be treatable therewith, providing additional therapy for patients with a hide to treat disease. PHOSITA is constantly seeking ways to improve cancer therapies, especially those for chemoresistant diseases and so would be highly motivated to combine these teachings and apply the obvious method to their patients with a reasonable expectation of success owed to the successes of Agatsuma in providing a functional therapy against TROP2+ cancers.
With respect to claims 39-40, Agatsuma teaches use of cisplatin in their ADC against Trop2-expressing cancers (Agatsuma et al, column 62, paragraph 2). PHOSITA is constantly seeking ways to improve cancer therapies, especially those for chemoresistant diseases and so would be highly motivated to combine these teachings and apply the obvious method to their patients with a reasonable expectation of success owed to the successes of Agatsuma in providing a functional therapy against TROP2+ cancers comprising administration of cisplatin conjugated to ADC 13 of Agatsuma.
Regarding claim 43, Shvartsur et al discloses Trop2 is an independent prognostic marker for cancer recurrence (Shvartsur et al, pg. 95 paragraph G. Gastric Cancer). Therefore, the patient population above with resistant disease could obviously have recurrent disease as the resistant disease is Trop2+. For the advantages above, better treating patients with an aggressive ovarian cancer, it would be obvious to combine the teachings using the ADC of Agatsuma against the recurrent disease.
With respect to claims 67-69, Agatsuma et al disclose use of the same TROP-2 ADC in lung adenocarcinoma (Calu-6, an NSCLC line; Agatsuma et al Column 122), breast cancer and urothelial cancer (Agatsuma et al, Column 167, claim 6).
Thus, the combined teachings render all claims above obvious.
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 23-28, 30-44, and 67-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9850312 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The patented claims are drawn to a Trop2 ADC and the method of using the TROP2 ADC in cancer.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
Claims 23-28, 30-44, and 67-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-92 of U.S. Patent No. 11273155 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The patented claims are drawn to an ADC consistent with ADC of the instant application and method of using for treating cancer.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
Claims 23-28, 30-44, and 67-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31, 63-88 of U.S. Patent No. 12220604 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The patented claims are drawn to a method of using the ADC of the instant application for treating cancer.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
Claims 23-28 and 30-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 12-15, 26-37 of U.S. Patent No. 11173213 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The patented claims are drawn to a method of producing the ADC of the instant application.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
Claims 23-28, 30-44, and 67-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11008398 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The patented claims are drawn to the ADC of the instant application.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
Claims 23-28, 30-44, and 67-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10-14 of U.S. Application No. 17/230543 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The copending claims are drawn to the ADC of the instant application and a method of producing the ADC.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
This is a provisional rejection.
Claims 23-28, 30-44, and 67-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 21-23, 26-28, 44, 46-52, 54, 56, 58, 59 of U.S. Application No. 17/269615 in view of Agatsuma et al (US9850312, filed 06/20/2016) and Shvartsur et al (Genes and Cancer, 2015, Vol. 6 (3-4)).
The claims above are all rendered obvious by the combined teachings of Agatsuma et al and Shvartsur et al. The reasons for this in the 103 above are incorporated here in their entirety. Addition of the patented or copending claims over related subject matter only further supports this finding of obviousness.
The copending claims are drawn to identifying a cancer patient to use the method of treating with the ADC of the instant application and a method of treating cancer patients with the ADC of the instant application.
Thus, the combination of the prior art with related products and/or methods to these claims renders all instant claims obvious.
This is a provisional rejection.
Conclusion
No claims are allowed.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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