DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
The remarks filed 12/30/2025 are acknowledged herein.
As before noted, Applicant elected the species of the invention in which the tyrosine kinase inhibitor is afatinib and the tumor is a “lung tumor including non-small cell lung tumor”.
Claims 58-68 and 70-73 are pending in the application. Claims 60, 61, and 64 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of the invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 21, 2024.
Claims 58, 59, 62, 63, and 65-68, and 70-73 are under examination.
Rejections Withdrawn
The rejection of claims 58, 59, 62, 63, 65-68, and 70-73 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,139,548 in view of Geuna (Breast Cancer (Dove Med Press). 2012 Aug 27;4:131-7, PTO-892 09/10/2024) is withdrawn in view of Terminal Disclaimer filed 12/30/2025.
Rejections Maintained
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.
Application No. 16/499,144
Claims 58, 59, 62, 63, 65-68, 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 66-91 of copending Application No. 16/499,144 in view of Roskoski (Pharmacol Res. 2014 Jan;79:34-74).
Regarding the instant claim 58, pertaining to a method comprising administration of the claimed ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitor, ‘144 claims 66 and 75 teach a method of treating human subject comprising administering a ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitors lapatinib and neratinib.
Regarding the antibody used in the methods of instant claims 58, 65-68, 70-72, ‘144 claims 66-68, 79-81 and 83-91 disclose the ErbB-2/ErbB-3 bispecific antibody identical to the instant invention. The instant disclosure Fig. 16A(i) teaches that the instant ErbB-2 heavy chain corresponds to MF3958, Fig. 16B(a) teaches that the instant ErbB-3 heavy chain corresponds to MF3178, and Fig. 16C teaches the common light chain SEQ ID NO:87 identical to ‘144 SEQ ID NO:74.
‘548 does not teach (1) wherein the tyrosine kinase is afatinib or (2) wherein the method is used for treatment of non-small cell lung tumor.
These deficiencies are taught by Roskoski.
The disclosure of Roskoski is directed to a review of the role of the ErbB (HER) family of protein kinases and cancer, specifically teaching that several malignancies are associated with the mutation or increased expression of member of the ErbB family including lung carcinoma (Abstract, Lines 16-18).
Regarding instant claim 59, wherein said tyrosine kinase is afatinib, Roskoski teaches afatinib is approved by the FDA for first-line treatment of NSCLC in patient bearing certain mutations, and thus may represent an effective therapy for patients who have developed resistance to other tyrosine kinase inhibitors (Pg. 55, Right column, Full paragraph 3, Lines 1-6).
Regarding instant claims 62, 63, and 73, wherein the tumor is a lung tumor (claims 62 and 63), specifically a non-small lung cell lung tumor (claim 73), Roskoski teaches the use of ErbB2-specific antibodies (e.g. trastuzumab) and tyrosine kinase inhibitors (e.g. afatinib) for treating non-small cell lung cancer (Pg. 56, Right column, Full paragraph 1, entire paragraph, also see cited references).
It would have been obvious to one having ordinary skill at the time of filing to have practiced the method to which the claims of the copending application ‘144 are directed by administering in combination with the bispecific antibody (1) a therapeutically effective amount of afatinib to treat a ErbB2- and/or ErbB3-expressing cancer and (2) to treat a non-small cell lung tumor. One would have been motivated to do so because Roskoski teaches the use of afatinib in the treatment of ErbB-2/ErbB-3 cancers and teaches the use of ErbB-specific antibodies for treatment of non-small cell lung cancer. There would be an expectation of success in using combination therapy comprising afatanib and using the ErbB-specific antibodies for non-small cell lung cancer for the treatment of ErbB-expressing cancers based on the art at the time teaching the use of both treatments for non-small cell lung cancer.
This is a provisional nonstatutory double patenting rejection.
Application No. 17/755,196
Claims 58, 59, 62, 63, 65-68, 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 17/755,196 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method of the co-pending application comprises the same bispecific antibody co-administered with afatinib and used in the treatment of non-small cell lung cancer.
Regarding the instant claims 58 and 59, pertaining to a method comprising administration of the ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitor afatinib (claim 59), ‘196 claims 1, 3 and 4 disclose a method of treating human subject comprising administering a ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitor afatinib.
Regarding the instant antibody used in the methods of instant claims 58, 65-68, 70-72, ‘196 claims 1, and 17-21 disclose the ErbB-2/ErbB-3 bispecific antibody identical to the instant invention. The instant disclosure Fig. 16A(i) teaches that the instant ErbB-2 heavy chain corresponds to MF3958, Fig. 16B(a) teaches that the instant ErbB-3 heavy chain corresponds to MF3178, and the ‘196 specification teaches the rearranged germline human kappa light chain is IgVKl-39*01/IGJK1*01 corresponds to the instant light chain with identical CDRs (‘196 specification Pg. 30).
Regarding instant claims 62, 63, and 73, wherein the tumor is a lung tumor (claims 62 and 63), specifically a non-small lung cell lung tumor (claim 73), ‘196 claims 9 and 10 disclose the cancer treated is non-small cell lung cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Application No. 18/251,832
Claims 58, 59, 62, 63, 65-68, 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-11, 13, 16-18, 21, 22, 28, and 32 of copending Application No. 18/251,832 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method of the co-pending application comprises the same bispecific antibody co-administered with afatinib and used in the treatment of non-small cell lung cancer.
Regarding the instant claim 58 and 59, pertaining to a method comprising administration of the ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitor afatinib (claim 59), ‘832 claims 1 and 22 disclose a method of treating human subject comprising administering a ErbB-2/ErbB-3 bispecific antibody with previous administration of tyrosine kinase inhibitor afatinib. The copending application method broadly but reasonably anticipates the instant methods which do not specify the time interval between the administration of the bispecific antibody and tyrosine kinase inhibitor.
Regarding the instant antibody used in the methods of instant claims 58, 65-68, 70-72, ‘832 claims 4-7 disclose the ErbB-2/ErbB-3 bispecific antibody identical to the instant invention. The instant ErbB-2 CDRs correspond to ‘832 SEQ ID NOs: 66, 67 and 68. The instant ErbB-3 CDRs correspond to ‘832 SEQ ID NOs: 111, 112, and 113. The instant light chain CDRs are disclosed in ‘832 SEQ ID NOs: 2, 3, and 4.
Regarding instant claims 62, 63, and 73, wherein the tumor is a lung tumor (claims 62 and 63), specifically a non-small lung cell lung tumor (claim 73), ‘832 claim 8 discloses the cancer treated is non-small cell lung cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Application No. 18/419,492
Claims 58, 59, 62, 63, 65-68, 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58-78 of copending Application No. 18/419,492 in view of Roskoski (Pharmacol Res. 2014 Jan;79:34-74).
Regarding the instant claim 58, pertaining to a method comprising administration of the claimed ErbB-2/ErbB-3 bispecific antibody, ‘492 claims 58, 72, 73, and 78 teach a method of treating human subject comprising administering a ErbB-2/ErbB-3 bispecific antibody.
Regarding the instant antibody used in the methods of instant claims 58, 65-68, 70-72, ‘492 claims 58, 65-73, 78 disclose the ErbB-2/ErbB-3 bispecific antibody identical to the instant invention. The instant disclosure Fig. 16A(i) teaches that the instant ErbB-2 heavy chain corresponds to MF3958, Fig. 16B(a) teaches that the instant ErbB-3 heavy chain corresponds to MF3178, and the ‘196 specification teaches the rearranged germline human kappa light chain is IgVKl-39*01/IGJK1*01 corresponds to the instant light chain with identical CDRs (‘492 specification Pg. 10).
Regarding instant claims 62, 63, and 73, wherein the tumor is a lung tumor (claims 62 and 63), specifically a non-small lung cell lung tumor (claim 73), ‘492 claims 60-62 and 74-76 disclose the cancer treated is non-small cell lung cancer.
‘492 does not teach wherein the bispecific antibody is co-administered with a tyrosine kinase inhibitor and wherein the tyrosine kinase inhibitor is afatinib.
These deficiencies are taught by Roskoski.
The disclosure of Roskoski is directed to a review of the role of the ErbB (HER) family of protein kinases and cancer, specifically teaching that several malignancies are associated with the mutation or increased expression of member of the ErbB family including lung carcinoma (Abstract, Lines 16-18).
Regarding instant claim 59, wherein said tyrosine kinase is afatinib, Roskoski teaches afatinib is approved by the FDA for first-line treatment of NSCLC in patient bearing certain mutations, and thus may represent an effective therapy for patients who have developed resistance to other tyrosine kinase inhibitors (Pg. 55, Right column, Full paragraph 3, Lines 1-6).
It would have been obvious to one having ordinary skill at the time of filing to have practiced the method to which the claims of the copending application ‘492 are directed by administering in combination with the bispecific antibody a therapeutically effective amount of afatinib to treat a ErbB2- and/or ErbB3-expressing cancer. One would have been motivated to do so because Roskoski teaches the use of afatinib in the treatment of ErbB-2/ErbB-3 cancers and teaches the use of ErbB-specific antibodies for treatment of non-small cell lung cancer. There would be an expectation of success in using combination therapy comprising afatanib and using the ErbB-specific antibodies for non-small cell lung cancer for the treatment of ErbB-expressing cancers based on the art at the time teaching the use of both treatments for non-small cell lung cancer.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/449,460
Claims 58, 59, 62, 63, 65-68, 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/499,460 in view of Roskoski (Pharmacol Res. 2014 Jan;79:34-74).
Regarding the instant claim 58, pertaining to a method comprising administration of the claimed ErbB-2/ErbB-3 bispecific antibody and tyrosine kinase inhibitor, ‘460 claims 1 and 7 teach a method of treating human subject comprising administering a ErbB-2/ErbB-3 bispecific antibody and ‘460 claim 17 teaches further administration of an ErbB-1 inhibitor.
Regarding the instant antibody used in the methods of instant claims 58, 65-68, 70-72, ‘460 claims 19-21 disclose the ErbB-2/ErbB-3 bispecific antibody identical to the instant invention. The instant disclosure Fig. 16A(i) teaches that the instant ErbB-2 heavy chain corresponds to MF3958, Fig. 16B(a) teaches that the instant ErbB-3 heavy chain corresponds to MF3178, and the ‘460 specification teaches the rearranged germline human kappa light chain is IgVKl-39*01/IGJK1*01 corresponds to the instant light chain with identical CDRs (‘460 specification Pg. 7).
Regarding instant claims 62, 63, and 73, wherein the tumor is a lung tumor (claims 62 and 63), specifically a non-small lung cell lung tumor (claim 73), ‘460 claims 6 and 8 disclose the cancer treated is non-small cell lung cancer.
‘460 does not teach wherein the bispecific antibody is co-administered with a tyrosine kinase inhibitor and wherein the tyrosine kinase inhibitor is afatinib.
These deficiencies are taught by Roskoski.
The disclosure of Roskoski is directed to a review of the role of the ErbB (HER) family of protein kinases and cancer, specifically teaching that several malignancies are associated with the mutation or increased expression of member of the ErbB family including lung carcinoma (Abstract, Lines 16-18).
Regarding instant claim 59, wherein said tyrosine kinase is afatinib, Roskoski teaches afatinib is approved by the FDA for first-line treatment of NSCLC in patient bearing certain mutations, and thus may represent an effective therapy for patients who have developed resistance to other tyrosine kinase inhibitors (Pg. 55, Right column, Full paragraph 3, Lines 1-6).
It would have been obvious to one having ordinary skill at the time of filing to have practiced the method to which the claims of the copending application ‘460 are directed by administering in combination with the bispecific antibody a therapeutically effective amount of afatinib to treat a ErbB2- and/or ErbB3-expressing cancer. One would have been motivated to do so because Roskoski teaches the use of afatinib in the treatment of ErbB-2/ErbB-3 cancers and teaches the use of ErbB-specific antibodies for treatment of non-small cell lung cancer. There would be an expectation of success in using combination therapy comprising afatanib and using the ErbB-specific antibodies for non-small cell lung cancer for the treatment of ErbB-expressing cancers based on the art at the time teaching the use of both treatments for non-small cell lung cancer.
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive.
The applicant traverses the double patenting rejections for the following reasons:
Claims to methods of treating cancer are not considered predictable. While the claimed elements “could” have been combined, this is not the legal standard, which states that potential solutions pertaining to the medical arts are unpredictable (Remarks, Pgs. 5 and 6).
The applications 17/755,196, 18/251,832, 18/419,492, 18/449,460 are directed to administration of the bispecific antibody to specific patient populations and do not suggest combination therapy (Remarks, Pgs. 7-8).
In response, despite the inherent unpredictability in the medical arts, combination therapy for cancer is extremely common and widely implemented, particularly with well-known agents such as antibodies specific for HER2 and HER3 and tyrosine kinases as claimed. A determination of obviousness requires a reasonable expectation of success, not an absolute expectation of success.
Pertaining to the argument that the co-pending applications are directed to administration of the antibody to specific patient populations, the inventions of co-pending 17/555,196, 18/251,832, 18/419,492, and 18/449,460 are all directed a method of treating a subject with ERBB2, ERBB3, or ERBB2/ERBB3-positive cancer comprising administration of the instant bispecific antibody, which anticipates the instant claim limitation which states “a method of treating a human subject having an ErbB-2, ErbB-3 or ErbB-2/ErbB-3 positive tumor”. The specific patient populations of the co-pending patient populations all fall within the instant claimed patient population.
For these reasons, the provisional double patenting rejections are maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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