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 67-96 are pending and currently under consideration.
Claim Objections
Claim 70 is objected to because of an apparent typographical issue. Claim 70 awkwardly recites “…is administered…or one every two weeks.” It is suspected Applicant intends claim 70 to recite: “…or once every two weeks.” Proper correction is required.
Claims 74-75 are objected to because of apparent typographical issues. Claims 74-75 describe amounts as concentrations. Amending claims 74-75 to replace instances of “a concentration” with “an amount” would obviate this objection. Proper correction is required.
Claim 74 is further objected to because of an apparent typographical issue. It appears the word “administration” after “weekly” is out of place and should be deleted. Proper correction is required.
Claim 96 is objected to because of an apparent typographical issue. It appears “or suitable” after “10 mg/kg” is out of place and should be deleted. Proper correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 67-94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating Alzheimer’s disease in a subject comprising administering (i) an anti-Ab protofibril antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising SEQ ID NO:13 and a light chain variable domain comprising SEQ ID NO:14; and (ii) an anti-tau antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising SEQ ID NO:15 and a light chain variable domain comprising SEQ ID NO:16, does not reasonably provide enablement for a method of treating or preventing Alzheimer’s disease in a subject comprising administering (i) an anti-Ab protofibril antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:13 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:14; and (ii) an anti-tau antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:15 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:16. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are drawn to a method of treating or preventing Alzheimer’s disease in a subject comprising administering (i) an anti-Ab protofibril antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:13 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:14; and (ii) an anti-tau antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:15 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:16. The term “treat” means “obtaining one or more beneficial or desired results” (as defined by [0029] of the instant specification). The term “prevent” includes “prophylactic benefit” (as defined by [0030] of the instant specification). The examiner is interpreting “an amino acid sequence of” a recited SEQ ID NO to encompass as few as two consecutive amino acids of the SEQ ID NO. Therefore, the claims encompass methods of treating or preventing Alzheimer’s disease in a subject comprising administering (i) an anti-Ab protofibril antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:13 and a light chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:14; and (ii) an anti-tau antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:15 and a light chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:16.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification prophetically discloses claimed methods. The specification does not provide any results of methods encompassed by the claims.
The prior art teaches (i) an anti-Ab protofibril antibody for treating Alzheimer’s comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:13 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:14 (Nerelius et al (US 2016/0009793 A1; 1/14/2019; 2/24/25 IDS)) and (ii) an anti-tau antibody for treating Alzheimer’s comprising a heavy chain variable domain comprising “an amino acid sequence of” SEQ ID NO:15 and a light chain variable domain comprising “an amino acid sequence of” SEQ ID NO:16 (Roberts et al (US 2019/0112365 A1; 4/18/2019)). The prior art does not teach antibodies encompassed by the claims “prevent” Alzheimer’s. Further, the prior art does not each just any combination of antibodies broadly encompassed by the claims (see: “an amino acid sequence of”) treats or prevents Alzheimer’s.
Reasonable guidance with respect to preventing any disorder relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to the disorder This type of data might be derived from widespread genetic analysis, cancer clusters, or family histories. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical disease and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to methods of treating or preventing Alzheimer’s disease in a subject comprising administering (i) an anti-Ab protofibril antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:13 and a light chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:14; and (ii) an anti-tau antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:15 and a light chain variable domain comprising as few as two consecutive amino acids of SEQ ID NO:16, and Applicant has not enabled said methods because undue experimentation would be required to determine which combinations of antibodies broadly encompassed by the claims (see “an amino acid sequence of”) are capable of (or are not capable of) preventing and/or treating Alzheimer’s disease when administered to a subject in order to perform the method as broadly claimed.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
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.
Claims 67-96 are rejected under 35 U.S.C. 103(a) as being unpatentable over Nerelius et al (US 2016/0009793 A1; 1/14/2019; 2/24/25 IDS) in view of Roberts et al (US 2019/0112365 A1; 4/18/2019).
Nerelius et al teaches Ab protofibril was identified as a target for Alzheimer’s disease based on studies in which an inherited mutation in APP that was found to be linked to Alzheimer’s patients caused increased formation of Ab protofibril ([0004], in particular). Nerelius et al teaches BAN2401 ([0053]-[0054], in particular), which is a humanized anti-Ab protofibril antibody comprising a heavy chain variable domain comprising SEQ ID NO:13 (identical to instant SEQ ID NO:13) and a light chain variable domain comprising SEQ ID NO:7 (identical to instant SEQ ID NO:14). Nerelius et al further teaches a method of treating Alzheimer’s in a subject having, or being at risk of developing Alzheimer’s, comprising administering to said subject a therapeutically effective amount of BAN2401 ([0034], in particular). Nerelius et al further teaches said method wherein BAN2401 is administered at doses from 0.01 to 100 mg/kg/dose administered intravenously (i.v.) or subcutaneously (s.c.) daily, weekly, quarterly, or less ([0111], in particular). Nerelius et al further teaches administering BAN2401 intravenously at a dosage of 10 mg/kg ([0134]-[0136], in particular).
Nerelius et al further teaches the method wherein drugs targeting Tau are combined with the BAN2401 treatment ([0123]-[0125], in particular). Nerelius et al further teaches compositions comprising doses of BAN2401 and drugs targeting Tau ([0125], in particular). Nerelius et al further teaches the method wherein the heavy chain of BAN2401 comprises SEQ ID NO:23 ([0107], which is identical to instant SEQ ID NO:17. Nerelius et al further teaches the method wherein the light chain of BAN2401 comprises SEQ ID NO:24 ([0108], which is identical to instant SEQ ID NO:18.
Nerelius et al does not specifically teach any particular anti-Tau antibody. However, these deficiencies are made up in the teachings of Roberts et al.
At [0007], Roberts et al teaches anti-Tau antibody comprising a heavy chain variable domain comprising SEQ ID NO:402 (identical to instant SEQ ID NO:15) and a light chain variable domain comprising SEQ ID NO:572 (identical to instant SEQ ID NO:16). Roberts et al further teaches a method of treating Alzheimer’s comprising administering the anti-Tau antibody ([0015], in particular). Roberts et al further teaches said method wherein the anti-Tau antibody is administered at doses from 1 mg/kg to 100 mg/kg administered intravenously (i.v.) or subcutaneously (s.c.) weekly or every three weeks ([0144], in particular). Roberts et al further teaches the method wherein a higher loading dose is followed by one or more lower doses ([0142] and [0145], in particular). Roberts et al further teaches the method wherein the heavy chain of the anti-Tau antibody comprises SEQ ID NO:404 (Table 1), which is identical to instant SEQ ID NO:19. Roberts et al further teaches the method wherein the light chain of the anti-Tau antibody comprises SEQ ID NO:574 (Table 1), which is identical to instant SEQ ID NO:20.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the method of Nerelius et al wherein just any subject having (and symptomatic for) Alzheimer’s disease or suspected of having Alzheimer’s disease (including those without any symptoms), are administered BAN2401 of Nerelius et al in combination with he anti-Tau therapeutic of Roberts et al because Nerelius et al teaches treating Alzheimer’s wherein drugs targeting Tau are combined with the BAN2401 treatment ([0123]-[0125], in particular) and the anti-Tau therapeutic of Roberts et al is a drug targeting Tau. This is an example of both combining prior art elements according to known methods to yield predictable results and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein BAN2401 of Nerelius et al and the anti-Tau therapeutic of Roberts et al are administered at just any doses encompassed by Nereluius et al and/or Roberts et al, via any administration routes of Nereluius et al and/or Roberts et al, in any sequential order, and at any schedule broadly encompassed by Nereluius et al and/or Roberts et al. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Further, optimizing dosage amounts, administration routes, and administration schedules are examples of know result-effective variables used to alter levels of administered therapeutics in a subject that correlate with best therapeutic results. See MPEP 2144.05.
Further, all reagents of a method are a “kit”. Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art to combine the reagents of the combined method into a kit format since a kit provides a quality control, saves money, and saves resources.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 36-37 of U.S. Patent No. 10829547 in view of Nerelius et al (US 2016/0009793 A1; 1/14/2019; 2/24/25 IDS); and
claims 11-12 of U.S. Patent No. 11578120 in view of Nerelius et al (US 2016/0009793 A1; 1/14/2019; 2/24/25 IDS).
The patent claims and the instant claims are both drawn to the same anti-Tau therapeutic and methods of using the anti-Tau therapeutic to treat Alzheimer’s. The instant claims differ from the patent claims in that the instant claims further recite an anti-Ab protofibril antibody or antigen binding fragment thereof (such as BAN2401 of Nerelius et al).
Teachings of Nerelius et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the methods of the patents wherein just any subject having (and symptomatic for) Alzheimer’s disease or suspected of having Alzheimer’s disease (including those without any symptoms), are administered BAN2401 of Nerelius et al in combination with the anti-Tau therapeutics of the patents because Nerelius et al teaches treating Alzheimer’s wherein drugs targeting Tau are combined with the BAN2401 treatment ([0123]-[0125], in particular) and the anti-Tau therapeutics of the patents are drugs targeting Tau.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein BAN2401 of Nerelius et al and the anti-Tau therapeutic of the patents are administered at just any doses encompassed by Nereluius et al and/or disclosed by the patents, via any administration routes of Nereluius et al and/or the patents, in any sequential order, and at any schedule broadly encompassed by Nereluius et al and/or the patents. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Further, optimizing dosage amounts, administration routes, and administration schedules are examples of know result-effective variables used to alter levels of administered therapeutics in a subject that correlate with best therapeutic results.
Further, all reagents of a method are a “kit”. Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art to combine the reagents of the combined method into a kit format since a kit provides a quality control, saves money, and saves resources.
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10358485 in view of Roberts et al (US 2019/0112365 A1; 4/18/2019) and Nerelius et al (US 2016/0009793 A1; 1/14/2019; 2/24/25 IDS).
The patent claims and the instant claims are both drawn to the same anti-Tau therapeutic. The instant claims differ from the patent claims in that the instant claims further recite an anti-Ab protofibril antibody or antigen binding fragment thereof (such as BAN2401 of Nerelius et al) and administering the anti-Ab protofibril antibody or antigen binding fragment thereof to treat Alzheimer’s in combination with the anti-Tau antibody.
Teachings of Roberts et al and Nerelius et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the methods of Roberts et al to treat Alzheimer’s by administering the anti-Tau antibody of the patent wherein just any subject having (and symptomatic for) Alzheimer’s disease or suspected of having Alzheimer’s disease (including those without any symptoms), are administered BAN2401 of Nerelius et al in combination with the anti-Tau therapeutics of the patent because Nerelius et al teaches treating Alzheimer’s wherein drugs targeting Tau are combined with the BAN2401 treatment ([0123]-[0125], in particular) and the anti-Tau therapeutics of the patents are drugs targeting Tau.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein BAN2401 of Nerelius et al and the anti-Tau therapeutic of the patent are administered at just any doses encompassed by Nereluius et al and/or taught by Roberts et al, via any administration routes of Nereluius et al and/or taught by Roberts et al, in any sequential order, and at any schedule broadly encompassed by Nereluius et al and/or taught by Roberts et al. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Further, optimizing dosage amounts, administration routes, and administration schedules are examples of know result-effective variables used to alter levels of administered therapeutics in a subject that correlate with best therapeutic results.
Further, all reagents of a method are a “kit”. Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art to combine the reagents of the combined method into a kit format since a kit provides a quality control, saves money, and saves resources.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
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