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 .
The specification does not specifically identify or name the bispecific antibody having the sequences recited in instant claims 24-27. Applicant is requested to make clear on the record whether or not these sequences correspond to the sequences in AMG 596, currently known as etevritamab. See at least paragraphs [0015 and 0068] and Examples 1-4 of the specification.
With respect to claim 12, applicant is requested to confirm that a polyethylsulfone (PES) filter was intended. Note that Example 4 uses a polyethersulfone filter. The examiner was not able to identify a polyethylsulfone (PES) filter in the prior art. See by comparison Lowy et al. (U.S. Patent Application Publication 2013/0129722) disclosing a polyethersulfone inline filter at paragraphs [0194 and 0229-0230].
Specification
The disclosure is objected to because of the following informalities:
The incorporation of sequence listing (paragraph [0002] of the specification) should reference the size of the file in bytes not kilobytes (KB). See MPEP 2422.03(I).
Appropriate correction is required.
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 1-2, 9, 11, 13, 18-20, and 22-31 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) and Meyer et al. (U.S. Patent Application Publication 20100216667).
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 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, 23, and 31. 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.
Rosenthal et al. (of record) discloses administration of AMG 596 (an EGFRvIII x CD3 bispecific antibody) 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].
Abel et al., Rosenthal et al., and Raum 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 24-28. Abel et al specifically discloses that the antibodies can be formulated in a plastic administration container preferably made of EVA, polyolefin, and/or PVC. 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 using 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 1-2 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. The kits of instant claims 29-31 are suggested by the prior art.
Claims 1, 11, 14, and 29-30 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) and Meyer et al. (U.S. Patent Application Publication 20100216667). as applied to claims 1-2, 9, 11, 13, 18-20, and 22-31 above, and further in view of Gonsalves (U.S. Patent Application Publication 2017/0333628).
The methods of claims 1 and 11 and kits of claims 29-30 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 claims 14 and 29 (as a second embodiment).
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) and Meyer et al. (U.S. Patent Application Publication 20100216667). 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 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Abel et al. (WO 2018/204907) in view of Rosenthal et al. (of record), Raum et al. (U.S. Patent Application Publication 2017/0029512) and Meyer et al. (U.S. Patent Application Publication 20100216667). as applied to claims 1-2, 9, 11, 13, 18-20, and 22-31 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 disclose a CADD infusion pump as recited in instant claim 15 and 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) and Meyer et al. (U.S. Patent Application Publication 20100216667). 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.
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 1 and 3-31 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.
The term “substantially lacks polyvinyl chloride (PVC) or a PVC plasticizer” in claims 1 and 30-31 is a relative term which renders the claim indefinite. The term “substantially lacks polyvinyl chloride (PVC) or a PVC plasticizer” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The example of comprising less than about 5% in paragraph [0046] is not a limiting definition.
The term “substantially lacks air” in claims 29 is a relative term which renders the claim indefinite. The term “substantially lacks air” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The example of comprising less than about 5% in paragraph [0047] is not a limiting definition.
Claim 10 is confusing in reciting “wherein the anti-EGFRvIII agent is administered to the subject at a dose of from 3000 ug/day to 6000 ug/day, at a 14-day on / 14-day off cycle, or a 28-day on / 14-day off cycle.” As written, it is unclear if the claim intended administering to the subject at (a) a dose of from 3000 µg/day to 6000 µg/day, (b) a 14-day on/14-day off cycle, or (c) a 28-day on/14-day off cycle or if the claim intended administering to the subject (a) at a dose of from 3000 µg/day to 6000 µg/day in a 14-day on/14-day off cycle or (b) at a dose of from 3000 µg/day to 6000 µg/day in a 28-day on/14-day off cycle or if something else was intended.
Claim 12 is confusing in its dependency upon claim 11. Claim 11 may include a filter but does not require a filter. It is unclear what the infusion system of claim 12 must include.
Claim 13 is confusing in its dependency upon claim 11. Claim 11 may include an IV bag but does not require an IV bag. It is unclear what the infusion system of claim 13 must include.
Claim 15 is indefinite in reciting a “CADD pump.” This appears to be a trademarked product. See at least Example 2. Claim 15 contains the trademark/trade name “CADD pump.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe “CADD pump” and, accordingly, the identification/description is indefinite.
Claim 20 is confusing in reciting intravenous saline solution (IVSS) in the recited percentages. It appears that applicant may have intended intravenous solution stabilizer (IVSS) (see paragraph [0053]). The specification does not appear to specifically identify what constitutes an intravenous saline solution.
Claim 29 does not clearly define what must be included in the kit. In particular, it is unknown what components are intended to be included in the administration system. In particular, it is unclear what defines the EGFRvIII agent structurally and functionally in this claim. Note that this is an independent claim. It is unknown if the EGFRvIII agent is packaged in some manner. It is unknown if the EGFRvIII is in the recited aqueous solution. Dependent claim 30 does not remedy the deficiencies of the claim. An infusion line alone does not define an administration system or infusion system. The metes and bounds of claims 29-30 cannot be determined.
Claim 31 is confusing in reciting “IVSS and saline.” “IVSS” stands for intravenous saline solution (see E35 in paragraph [0007]) or intravenous solution stabilizer (see paragraph [0053]). The specification does not appear to specifically identify what constitutes an intravenous saline solution. It is unclear what was intended. In particular, it is unclear what defines the EGFRvIII agent structurally and functionally in this claim. Note that this is an independent claim. The metes and bounds of the claim cannot be determined.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 is directed to a method of treating an EGFRvIII-positive cancer or tumor in a subject by administering an anti-EGFRvIII x CD3 bispecific antibody using an infusion system where the infusion line substantially lacks polyvinyl chloride (PVC) or PVC plasticizer. Claims 3-8 have limitations with respect to the post-infusion solution particle count. These claims do not further limit the subject matter of claim 1. These claims do not further define the method of treatment. They speak to evaluating solutions after the infusion step of claim 1 has occurred. They are not treatment steps. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 22 depends upon claim 21. Claim 21 requires a concentration of less than 75 ng/ml. Claim 22 broadens rather than further limits claim 21 by reciting a concentration of about 75 ng/ml to about 500 ng/ml. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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