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 .
Claims 2-8, 10, 15, 21, 24, and 29-31 have been cancelled.
Claim 10 has now been cancelled and its limitations incorporated into independent claim 1.
The final Office Action mailed 4/15/2026 indicated that claim 10 was objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims and indicated that the prior art of record did not suggest the dosage regimens set forth in claim 10 for the bispecific antibody of claim 1 according to the claimed method of administration. After further consideration of the prior art of record, Kast et al. (WO 2021/092217, of record), discloses these limitations.
Finality of the rejection of the last Office action is hereby withdrawn. This Office action is being made non-final in view of the amended grounds of rejection.
The 7/15/2026 after final amendment has been entered.
As acknowledged by applicant at page 8 of the 2/9/2026 response, the bispecific antibody sequences now recited in claim 1 correspond to the sequences in AMG 596, currently known as etevritamab. Applicant’s 7/15/2026 response confirmed the identity of the sequences recited in claims 25-28 as the corresponding sequences of AMG 596. Specifically, SEQ ID NOs: 9 and 10 are the VH and VL amino acid sequences of the EGFRvIII-binding domain and SEQ ID NOs: 102 and 103 are the VH and VL amino acid sequences of the CD3-binding domain of AMG 596 (claim 25); SEQ ID NO: 11 is the EGFRvIII-binding domain and SEQ ID NO: 104 is the CD3-binding domain of AMG 596 (claim 26); SEQ ID NO: 12 is the amino acid sequence of AMG 596 (claim 27); and SEQ ID NO: 13 is the amino acid sequence of SEQ ID NO: 12 further comprising a C-terminal hexahistidine tag (claim 28).
Specification
The 7/15/2026 amendment to paragraph [0002] of the specification is acknowledged.
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.
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, 9, 11, 13, 18-20, 22-23, and 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Abel et al. (WO 2018/204907) in view of Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667) and Kast et al. (WO 2021/092217, of record).
Abel et al. (WO 2018/204907, published 8 November 2018, filed 7 May 2018) discloses administering EGFRviii x CD3 bispecific antibodies by continuous IV infusion to treat malignancies. The antibodies can be formulated in a plastic administration container preferably made of EVA, polyolefin, and/or PVC. The bispecific antibody AMG 596 (an EGFRvIII x CD3 bispecific antibody having the sequences recited in instant claim 1 as set forth above) is disclosed. See at least paragraph [0377]. Bispecific antibody concentrations of 0.5 µg/ml (i.e. 500 ng/ml, see claim 22) are disclosed. See at least abstract. Infusion bags having a total volume of 109 ml are disclosed. IV infusion bags having 0.9% (v/v) saline solution for continuous intravenous infusion are disclosed. IV infusion bags including 4% intravenous stabilizing solution (IVSS) are disclosed. See at least paragraphs [0368 and 0378-0381]. See instant claims 19-20 and 23. Kits having containers (such as bags of any material) containing the antibody, pumps, and infusers are disclosed. See at least paragraphs [0312-0313]. See at least claims, particularly claims 1, 15, 21, and 30-33; paragraphs [0006, 0008, 0012, 0027, 0034, 0041-0044, 0051, 0069-0070, 0288-0290, 0336]; and Figure 6. The reference does not disclose what type of infusion line is used or the administration dosages recited in claim 1.
Rosenthal et al. (of record) discloses administration of AMG 596 (an EGFRvIII x CD3 bispecific antibody having the sequences recited in instant claim 1 as set forth above) by continuous intravenous infusion to treat glioblastoma and references clinical trial NCT03296696. The reference does not disclose what type of infusion line is used.
Raum et al. (U.S. Patent Application Publication 2017/0029512) discloses administering an EGFRvIII x CD3 bispecific antibody to treat glioblastoma. The first binding domain binds human and macaque EGFRvIII. The second domain binds human CD3. See at least [0007, 0383]; Figure 1 and claim 1. See Table 4 for SEQ ID NOS: 100 and 151-160. SEQ ID NO: 160 (506 amino acids) is a sequence for the bispecific antibody of Raum et al. The antibody can have a hexahistidine tag at the C-terminus. See at least paragraph [0235]. Instant SEQ ID NO: 13 corresponds to instant SEQ ID NO: 12 with a hexahistidine tag at the C-terminus. (See instant claim 28.) The antibody can be administered by continuous infusion. Kits having containers (such as bags of any material) containing the antibody, pumps, and infusers are disclosed. See at least paragraphs [0364] and [0380]. SEQ ID NO: 160 is identical to instant SEQ ID NO: 12 and contains instant SEQ ID NOS: 9 (amino acids 1-124 of SEQ ID NO: 12), 10 (amino acids 140-251 of SEQ ID NO: 12), 102 (amino acids 258-382 of SEQ ID NO: 12), and 103 (amino acids 398-506 of SEQ ID NO: 12). Instant SEQ ID NO: 11 corresponds to amino acids 1-251 of instant SEQ ID NO: 12. Instant SEQ ID NO: 104 corresponds to amino acids 258-506 of instant SEQ ID NO: 12. SEQ ID NO: 100 (249 amino acids) of Raum et al. corresponds to instant SEQ ID NO: 104. The CDRs recited in instant claim 24 are present in SEQ ID NO: 160 of Raum et al. The reference does not disclose what type of infusion line is used.
Meyer et al. (U.S. Patent Application Publication 2010/0216667) discloses that typical IV bags and infusion lines include those made from polyolefins (POE), polyvinyl chloride (PVC), and ethylene vinyl acetate (EVA). Table 1 and Example 1 test the compatibility of pharmaceuticals and materials for their packaging, dosing, storage, and administration. Methods of screening for compatibility are disclosed and claimed. See at least paragraphs [0003-0006, 0074].
Kast et al. (WO 2021/092217) was published 14 May 2021 and filed 5 November 2020. Kast et al. claims, and is entitled to, benefit of the 62/931,975 priority document filed 7 November 2019. This date is prior to the instant application’s provisional application 63/077,088 priority date of 11 September 2020. Note that Kast et al. has no inventors in common with the instant application. Kast et al. has a common applicant (Amgen, Inc.) with the instant application; however, Kast et al. also has applicant Amgen Research (Munich) GMBH. Kast et al. is valid prior art under 102(a)(2). Kast et al. discloses a dosage regimen for anti-EGFRVIII agents for treating cancer. Dosages from 3000 ug/day to 60000 ug/day and 14-day on / 14-day off cycles and 28-day on / 14 day-off cycles are disclosed. See at least claims 1, 7, and 17. The EGFRvIII agent can be AMG 596. See at least paragraph [0020-0021] on page 17 and sequences in claims 1 and 3-4. The EGFRvIII agent can be administered by intravenous infusion, including continuous IV (cIV) infusion. Infusion lines using preprogrammed infusion pumps is disclosed. See at least E36 and E38 on pages 7-8 and paragraph [0080] on page 32.
Abel et al., Rosenthal et al., Raum et al., and Kast et al. disclose administering EGFRvIII x CD3 bispecific antibodies by continuous IV infusion to treat malignancies such as glioblastoma. In particular, Raum et al. discloses an EGFRvIII x CD3 bispecific antibody having the binding properties recited in claim 1 and the sequence characteristics recited in claims 1 and 25-28. Abel et al specifically discloses that the antibodies can be formulated in a plastic administration container preferably made of EVA, polyolefin, and/or PVC (i.e. each one individually). Meyer et al. discloses that typical IV bags and infusion lines include those made from polyolefins (POE), polyvinyl chloride (PVC), and ethylene vinyl acetate (EVA). It would have been obvious to use IV bags and infusion lines made from POE and/or EVA as taught by Meyer et al. and as suggested by Abel et al. in the methods taught by Abel et al., Rosenthal et al., and Raum et al. thereby meeting the limitations of claims 1 and 9. The IV bag limitations and pump limitations of instant claims 11 and 13 are suggested by Abel et al., Raum et al., and Meyer et al. It would have been obvious to use the suggested IV bags and infusion lines to administer an EGFRvIII x CD3 bispecific antibody, including AMG 596, according to the dosage schedule (dosages from 3000 ug/day to 60000 ug/day and 14-day on / 14-day off cycles and 28-day on / 14 day-off cycles) taught by Kast et al. to treat malignancies such as glioblastoma.
Claims 1 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Abel et al. (WO 2018/204907) in view of Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667) and Kast et al. (WO 2021/092217, of record), as applied to claims 1, 9, 11, 13, 18-20, 22-23, and 25-28 above, and further in view of Nakashima et al. (U.S. Patent Application Publication 2004/0031744).
The methods of claims 1 and 11 are obvious for the reasons set forth above. The references do not discuss the filter as recited in instant claim 12.
Nakashima et al. discloses that it would have been conventional to use polyethersulfone filters during infusion. See at least abstract; paragraphs [0002 and 0018], and claim 7.
It would have been obvious to use a polyethersulfone filter as suggested by Nakashima et al. in the method suggested by Abel et al. (WO 2018/204907), Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667), and Kast et al. (WO 2021/092217, of record). One would have been motivated to do so in order to avoid getting particulates in the tubing or being administered to the patient. The filter of Nakashima et al. meets the limitations of instant claim 12.
Claims 1, 11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Abel et al. (WO 2018/204907) in view of Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667), and Kast et al. (WO 2021/092217, of record), as applied to claims 1, 9, 11, 13, 18-20, 22-23, and 25-28 above, and further in view of Gonsalves (U.S. Patent Application Publication 2017/0333628).
The methods of claims 1 and 11 are obvious for the reasons set forth above. The references do not discuss the volume of air in the IV bag as recited in instant claim 14.
Gonsalves makes clear that it would be desirable to have as little air as possible in the IV bag and that preferably all of the air would be removed from the IV bag prior to infusion. See at least abstract and paragraphs [0064, 0112, and 0129].
It would have been obvious to use IV bags having little or no air in them as suggested by Gonsalves in the method suggested by Abel et al. (WO 2018/204907), Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667), and Kast et al. (WO 2021/092217, of record). One would have been motivated to do so in order to avoid getting air in the tubing or having air bubbles administered to the patient.
Claims 1, 11, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Abel et al. (WO 2018/204907) in view of Rosenthal et al. (2019, of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667), and Kast et al. (WO 2021/092217, of record), as applied to claims 1, 9, 11, 13, 18-20, 22-23, and 25-28 above, and further in view of DeBelser et al. (U.S. Patent Application Publication 2011/0137239).
The methods of claims 1 and 11 are obvious for the reasons set forth above. The references do not the features in instant claims 16-17.
DeBelser et al. discloses infusion pumps, including a CADD infusion pump, that would have been well known to those of ordinary skill in the art at the time of the effective filing date. Infusion pumps can be programmable and lockable. (See instant claim 16.) The rate of therapy delivery can be set and changed. A rate of 15 ml/hr is disclosed. (See instant claim 17.) See at least abstract; paragraphs [0028-0030 and 0033]; and claims.
It would have been obvious to use infusion pumps as described by DeBelser et al. in the method suggested by Abel et al. (WO 2018/204907), Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512), Meyer et al. (U.S. Patent Application Publication 20100216667), and Kast et al. (WO 2021/092217, of record). One would have been motivated to do so as these infusion pumps would have been conventional in the art at the time of the effective filing date.
With respect to the obviousness rejections set forth above, the prior art indicates that PVC infusion tubing OR EVA infusion tubing or polyolefin (i.e. POE) infusion tubing could be used. One of ordinary skill in the art at the time of the effective filing date would have been motivated to use any one of them as known alternatives. As such, the claimed method is suggested by the combination of the prior art.
Applicant previously argued unexpected results in view of an incompatibility of the AMG 596 antibody with PVC infusion lines. As set forth in the prior Office action, while it might not have been known that the AMG 596 antibody had an incompatibility as described on page 9 of applicant’s 2/9/2026 arguments, the possibility of such an incompatibility would have been known and is not unexpected. As set forth above, Meyer et al. discloses testing the compatibility of pharmaceuticals and materials for their packaging, dosing, storage, and administration. Methods of screening for compatibility are disclosed and claimed. Those of ordinary skill in the art would have been aware of other antibodies that were incompatible with PVC. Again, see at least abstract of Kumru et al. (2012, of record) with respect to increased particle formation by IgG4 monoclonal antibodies in PVC intravenous bags versus polyolefin intravenous bags. Again, see at least abstract of Jin et al. (2017) with respect to evaluating drug sorption to PCV- and non-PVC-based infusion tubes. Kumru et al. and Jin et al. establish that compatibility of drugs with various materials was a known problem with known methods of evaluation and known solutions (i.e. pick a different or better infusion line material). It would have been obvious to test for such incompatibilities and choose appropriate infusion line materials. No unexpected results have been demonstrated.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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