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 1, 3-9, 11-20 and 22 are under consideration in the instant Office Action.
Maintained Rejections
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-7, 11-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Mercken et al., US2018/0265575 (2/15/2023 PTO-892) in view of Qureshi et al., 2018 (4/9/2024, PTO-892).
Mercken teaches using humanized Tau monoclonal antibodies to treat tauopathies including Alzheimer’s disease and mild cognitive impairment Alzheimer’s disease (see paragraphs 3, 5, 35, 158 and claims 18-19) as in instant claims 1 and 22. Mercken teaches using the claimed, humanized antibodies to treat AD which is a human disease (see paragraph 7) and therefore, meets the requirement of a human subject in instant claim 1. Mercken’s teaching also support the idea that the administration of the pharmaceutical composition is safe and tolerable, as required in instant claim 1, since it is being administered to a human subject. Mercken teaches the instantly claimed antibody in the disclosed B296 antibody (see Tables 1-2) which is the same antibody as claimed in claims 1 and 3-7. Mercken teaches that the instantly claimed B296 antibody is an IgG1 isotype and that the preferred immunoglobulin isotypes are IgG1, IgG2, IgG3 and IgG4 (see paragraphs 72, 136-141 and 267) as required in instant claim 1. Mercken teaches the CDRs in the SEQ ID NOs: 7-9 and 19-21 (see Table 2 on page 8) which are the same sequences of SEQ ID NOS: 1-3 and 13-15 of instant claims 1 and 3. Mercken teaches the B296 antibody heavy and light chain variable regions as SEQ ID NOs: 27 and 31 (see Table 1 on page 7) which are the same sequences of SEQ ID NOS: 25 and 26 of instant claims 4 and 5. Mercken teaches the B296 antibody heavy and light chains as SEQ ID NOs: 45 and 46 (see Table 1 on page 7) which are the same sequences of SEQ ID NOS: 27 and 28 of instant claims 6 and 7. Mercken teaches administration of the monoclonal Tau antibody in a pharmaceutically acceptable carrier and therefore, a pharmaceutical composition (see paragraphs 33-35) as required in instant claims 1 and 18-20. Mercken teaches administering the pharmaceutical composition by intravenous infusion (see paragraphs 161 and 170) as required in instant claim 18. Mercken teaches administering the pharmaceutical composition as 1-10 separate doses and other doses administered at 1-4 months (see paragraph 170) as required in instant claims 19-20. While Mercken teaches the dose for a tau antibody for a mouse subject at about 20mg/kg (see Table 17), Mercken does not specifically teach the required dosage amounts of instant claims 1 and 11-17. Mercken does teach the therapeutically effective amount of the treatment can be determined by those skilled in the art based on the consideration of several factors including the disease to be treated, the symptoms involved, patient’s body mass, etc. to extrapolate the effective doses based on a dose curve (see paragraph 94).
Qureshi teaches administering anti-tau antibodies to human subjects that suffer from Alzheimer’s disease (see page 746, 1st column, 1st paragraph and page 2, 1st column, 1st paragraph) as required in instant claim 1. Qureshi teaches administering the dose of 21, 70, 210, 700, 2100, or 4200 mg of humanized monoclonal antibody BIIB092 intravenously (see page 746, abstract; page 748, Figure 1) as in instant claims 1, 11- 18. Qureshi teaches that the BIIB092 antibody serum concentration increased in dose proportional manner from 21 to 4200mg and that all the doses where safe and well tolerated (see paragraph spanning pages 749 and 751) as required in instant claim 1. Therefore, Qureshi provides a guidepost for a starting dosage treatment of human patient with an anti-tau antibody and specifically teaches the doses of instant claims 1, 11-16. Qureshi does not teach the specific antibodies of instant claims 1 and 3-7.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Mercken and Qureshi. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because both Mercken and Qureshi teach the administration of an anti-tau antibody to treat a tauopathy that includes Alzheimer’s disease. Further, Mercken teaches the therapeutically effective amount of the treatment can be determined by those skilled in the art based on the consideration of several factors including the disease to be treated, the symptoms involved, patient’s body mass, etc. to extrapolate the effective doses based on a dose curve (see paragraph 94). Qureshi teaches doses in the 210-4200mg range and one of ordinary skill in the art would be motivated to determine the therapeutically effective amount based on routine optimization of the method (see MPEP § 2144.05) to provide beneficially effective treatment in a patient suffering from Alzheimer’s disease. The Qureshi reference already teaches that increasing doses in the human patient population has a positive, detectable effect which is safe and well tolerated in humans and one of ordinary skill in the art would be motivated to try the doses up to the highest dose of 5000mg to determine the best dose to produce the best effect in the specific patient population suffering from Alzheimer’s with the instantly claimed antibodies. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claims 1, 3-9, 11-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Mercken et al., US2018/0265575 (2/15/2023 PTO-892) in view of Qureshi et al., 2018 (4/9/2024, PTO-892) and Shenoy US2018/0333493 (2/15/2023 PTO-892).
See Mercken and Qureshi as discussed above. Neither Mercken nor Qureshi teach the specific pharmaceutical composition set forth in instant claim 8 or the pH in instant claim 9.
Shenoy teaches compositions for low viscosity, high concentration therapeutic protein agent formulations that include antibodies (see abstract and paragraph 3). Shenoy teaches that high concentration of macromolecules like antibodies with low-viscosity are of great value for the ease of storage and delivery in vivo (see paragraph 3). Shenoy teaches that high concentrations of protein agents, including antibodies, must be handled with care due to the fact that they are prone to aggregation (see paragraph 4). Shenoy teaches that many protein-agent based therapeutics are administered intravenously (IV) and are often administered at high doses in a range of about 100 mg to about 1 g of protein agent per injection (see paragraph 6) as in instant claims 1, 13-14 and 18. Shenoy teaches that the concentration of a protein agent in a high concentration, low viscosity formulation may be about at least 500 mg/ml up to 2000 mg/ml (see paragraph 10) as in instant claims 1, 10-11 and 13-14. Shenoy teaches a formulation for low viscosity and reducing aggregation of the high concentration protein agents that include sucrose, histidine, EDTA, and polysorbate 20 (see paragraphs 212-215 and claims 23-26) as in instant claim 8. Shenoy teaches that the viscosity reducing agents, aggregation preventer and stabilizing agents for the formulation include sucrose, histidine, EDTA and polysorbate 20 (see paragraphs 240-241, and 251-252, 254 and 446) as in instant claim 8. One of ordinary skill in the art would be motivated to choose these components since there are known to be effective in preventing aggregation, stabilize the protein and produce a low viscosity formulation that are all preferred formulation aspects. Shenoy also teaches that these formulations also have pH 5.0-6.0 (see paragraphs 63, 65-72, 201, 446 and Table 1) as in instant claim 9.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Mercken, Qureshi and Shenoy. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Shenoy teaches that protein agents like antibodies in high concentrations require a specific formulation to provide a low-viscosity and non-aggregation antibody formulation be able to administer these high concentration dosages via an intravenous route to provide the optimal treatment dose to a subject in need. Since Mercken and Qureshi teach the use of high dose antibody concentration for treatment of a subject one of ordinary skill would use the teaching of Shenoy to produce a formulation for the instant antibody that would result in low-viscosity and non-aggregated antibodies. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-9, 11-20 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 and 22 of copending Application No. 17/509,889. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘889 claims a method of administering the same monoclonal antibody as in the instant claims 1, 3-7. The ‘889 claims an antibody with CRDs of SEQ ID NOs: 1-3 and 13-15 with heavy and light chain variable regions of SEQ ID NOs: 25-26 and heavy and light chains in SEQ ID NOs: 27-28 which are the same sequences and therefore, same antibodies as in the instant claims. ‘889 claims a dose of about 1mg/kg to about 60mg/kg and falls within the same claimed dose range of instant claims 1 and 11-17. ‘889 claims the administration of more than one dose and the separation of a dose about 4 weeks as in instant claims 18-19. ‘889 claims the same patient population of Alzheimer’s disease as in instant claims 20 and 22. ‘889 claims the same pharmaceutical composition of histidine, sucrose, polysorbate 20 and EDTA and pH 5.0-6.0 as in instant claims 8-9. Therefore, the instant claims are anticipated by ‘889.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-9, 11-20 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-14, 26 and 30-37 of U.S. Patent No. 10,766,953 in view of Qureshi et al., 2018 (4/9/2024, PTO-892) and Shenoy US2018/0333493 (2/15/2023 PTO-892). ‘953 claims the same monoclonal antibody and the method of administering the same monoclonal antibody as in the instant claims 1-7. The ‘953 claims an antibody with CRDs of SEQ ID NOs: 7-9 and 19-20 with heavy and light chains in SEQ ID NOs: 74 and 79 and encompass the heavy and light chain variable regions of SEQ ID NOs: 27 and 31 which are the same sequences as in the instant claims and therefore, same antibodies as in the instant claims. ‘953 also claims methods of treating tauopathies including Alzheimer’s disease and therefore, reads on a method of administering the antibodies as the instantly claimed method. ‘953 does not teach the specific dosage range or the specific formulation as in set forth in the instant claims.
Qureshi teaches administering anti-tau antibodies to human subjects that suffer from Alzheimer’s disease (see page 746, 1st column, 1st paragraph and page 2, 1st column, 1st paragraph) as required in instant claim 1. Qureshi teaches administering the dose of 21, 70, 210, 700, 2100, or 4200 mg of humanized monoclonal antibody BIIB092 intravenously (see page 746, abstract; page 748, Figure 1) as in instant claims 1, 11- 18. Qureshi teaches that the BIIB092 antibody serum concentration increased in dose proportional manner from 21 to 4200mg and that all the doses where safe and well tolerated (see paragraph spanning pages 749 and 751) as required in instant claim 1. Therefore, Qureshi provides a guidepost for a starting dosage treatment of human patient with an anti-tau antibody and specifically teaches the doses of instant claims 1, 11-16. Qureshi does not teach the specific antibodies of instant claims 1 and 3-7.
Shenoy teaches composition for low viscosity, high concentration therapeutic protein agent formulations that include antibodies (see abstract and paragraph 3). Shenoy teaches that high concentration of macromolecules like antibodies with low-viscosity are of great value for the ease of storage and delivery in vivo (see paragraph 3). Shenoy teaches that high concentrations of protein agents, including antibodies, must be handled with care due to the fact that there are prone to aggregation (see paragraph 4). Shenoy teaches that many protein-agent based therapeutics are administered intravenously (IV) and are often administered at high doses in a range of about 100 mg to about 1 g of protein agent per injection (see paragraph 6) as in instant claims 1, 13-14 and 18. Shenoy teaches that the concentration of a protein agent in a high concentration, low viscosity formulation may be about at least 500 mg/ml up to 2000 mg/ml (see paragraph 10) as in instant claims 1, 10-11 and 13-14. Shenoy teaches a formulation for low viscosity and reducing aggregation of the high concentration protein agents that include sucrose, histidine, EDTA, and polysorbate 20 (see paragraphs 212-215 and claims 23-26) as in instant claim 8. Shenoy teaches that the viscosity reducing agents, aggregation preventer and stabilizing agents for the formulation include sucrose, histidine, EDTA and polysorbate 20 (see paragraphs 240-241, and 251-252, 254 and 446) as in instant claim 8. One of ordinary skill in the art would be motivated to choose these components since there are known to be effective in preventing aggregation, stabilize the protein and produce a low viscosity formulation that are all preferred formulation aspects. Shenoy also teaches that these formulations also have pH 5.0-6.0 (see paragraphs 63, 65-72, 201, 446 and Table 1) as in instant claim 9.
The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Qureshi teach the administration of an anti-tau antibody to treat Alzheimer’s disease. Qureshi teach doses up to 4200mg range and one of ordinary skill in the art would be motivated to determine the therapeutically effective amount based on routine optimization of the method (see MPEP § 2144.05) to provide beneficially effective treatment in a patient suffering with Alzheimer’s disease. The Qureshi reference already teaches that increasing doses in the human patient population has a positive and detectable effect and one of ordinary skill in the art would be motivated to increase the doses up to the highest dose of 5000mg to determine the best dose to produce the best effect in the specific patient population suffering from a multitude of potential tauopathies. Shenoy teaches that protein agents like antibodies in high concentrations require a specific formulation to provide a low-viscosity and non-aggregation antibody formulation be able to administer these high concentration dosages via an intravenous route to provide the optimal treatment dose to a subject in need. Since Qureshi teaches the use of high dose antibody concentration one of ordinary skill would use the teaching of Shenoy to produce a formulation that would result in low-viscosity and non-aggregated antibodies that would be optimal for this type of administration.
Claims 1, 3-9, 11-20 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 9-11 of U.S. Patent No. 11,365,244 in view of Qureshi et al., 2018 (4/9/2024, PTO-892) and Shenoy US2018/0333493 (2/15/2023 PTO-892). ‘244claims the same monoclonal antibody and the method of administering the same monoclonal antibody as in the instant claims 1-7. The ‘224 claims an antibody with light chain variable regions of SEQ ID NOs: 27 and 31 with heavy and light chains in SEQ ID NOs: 45 and 46 and encompass the instantly claimed CDRS and which are the same sequences as in the instant claims and therefore, same antibodies as in the instant claims. ‘244 also claims methods of treating tauopathies including Alzheimer’s disease and therefore, reads on a method of administering the antibodies as the instantly claimed method. ‘244 does not teach the specific dosage range or the specific formulation as in set forth in the instant claims.
Qureshi teaches administering anti-tau antibodies to human subjects that suffer from Alzheimer’s disease (see page 746, 1st column, 1st paragraph and page 2, 1st column, 1st paragraph) as required in instant claim 1. Qureshi teaches administering the dose of 21, 70, 210, 700, 2100, or 4200 mg of humanized monoclonal antibody BIIB092 intravenously (see page 746, abstract; page 748, Figure 1) as in instant claims 1, 11- 18. Qureshi teaches that the BIIB092 antibody serum concentration increased in dose proportional manner from 21 to 4200mg and that all the doses where safe and well tolerated (see paragraph spanning pages 749 and 751) as now required in instant claim 1. Therefore, Qureshi provides a guidepost for a starting dosage treatment of human patient with an anti-tau antibody and specifically teaches the doses of instant claims 1, 11-16. Qureshi does not teach the specific antibodies of instant claims 1 and 3-7.
Shenoy teaches composition for low viscosity, high concentration therapeutic protein agent formulations that include antibodies (see abstract and paragraph 3). Shenoy teaches that high concentration of macromolecules like antibodies with low-viscosity are of great value for the ease of storage and delivery in vivo (see paragraph 3). Shenoy teaches that high concentrations of protein agents, including antibodies, must be handled with care due to the fact that there are prone to aggregation (see paragraph 4). Shenoy teaches that many protein-agent based therapeutics are administered intravenously (IV) and are often administered at high doses in a range of about 100 mg to about 1 g of protein agent per injection (see paragraph 6) as in instant claims 1, 13-14 and 18. Shenoy teaches that the concentration of a protein agent in a high concentration, low viscosity formulation may be about at least 500 mg/ml up to 2000 mg/ml (see paragraph 10) as in instant claims 1, 10-11 and 13-14. Shenoy teaches a formulation for low viscosity and reducing aggregation of the high concentration protein agents that include sucrose, histidine, EDTA, and polysorbate 20 (see paragraphs 212-215 and claims 23-26) as in instant claim 8. Shenoy teaches that the viscosity reducing agents, aggregation preventer and stabilizing agents for the formulation include sucrose, histidine, EDTA and polysorbate 20 (see paragraphs 240-241, and 251-252, 254 and 446) as in instant claim 8. One of ordinary skill in the art would be motivated to choose these components since there are known to be effective in preventing aggregation, stabilize the protein and produce a low viscosity formulation that are all preferred formulation aspects. Shenoy also teaches that these formulations also have pH 5.0-6.0 (see paragraphs 63, 65-72, 201, 446 and Table 1) as in instant claim 9.
The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Qureshi teach the administration of an anti-tau antibody to treat Alzheimer’s disease. Qureshi teach doses up to 4200mg range and one of ordinary skill in the art would be motivated to determine the therapeutically effective amount based on routine optimization of the method (see MPEP § 2144.05) to provide beneficially effective treatment in a patient suffering with Alzheimer’s disease. The Qureshi reference already teaches that increasing doses in the human patient population has a positive and detectable effect and one of ordinary skill in the art would be motivated to increase the doses up to the highest dose of 5000mg to determine the best dose to produce the best effect in the specific patient population suffering from a multitude of potential tauopathies. Shenoy teaches that protein agents like antibodies in high concentrations require a specific formulation to provide a low-viscosity and non-aggregation antibody formulation be able to administer these high concentration dosages via an intravenous route to provide the optimal treatment dose to a subject in need. Since Qureshi teaches the use of high dose antibody concentration one of ordinary skill would use the teaching of Shenoy to produce a formulation that would result in low-viscosity and non-aggregated antibodies that would be optimal for this type of administration.
Response to Amendment
The declaration under 37 CFR 1.132 filed 6/30/205 is insufficient to overcome the rejection of claim 1, 3-9, 11-20 and 22 based upon Mercken et al., US2018/0265575 (2/15/2023 PTO-892) in view of Qureshi et al., 2018 (4/9/2024, PTO-892) and Shenoy US2018/0333493 (2/15/2023 PTO-892). The reasons are discussed below.
Response to Arguments
Applicant's arguments filed 6/30/2025 have been fully considered but they are not persuasive. Applicant argues that the Mercken reference teaches one specific antibody to treat Alzheimer’s disease and that the Qureshi teaches a different antibody to treat Alzheimer’s and that one cannot infer dosage for these different antibodies because they target different epitopes in the tau protein. This is not found persuasive.
Applicant claims that the claimed dosage of the antibody is not taught by Mercken because the dose set for by Mercken was for the administration to mice. It is pointed out that the Mercken reference clearly sets forth that the target population to treat AD are human subjects and the Qureshi reference clearly teaches treating human subjects with Alzheimer’s disease with tau targeting antibodies. Therefore, the claimed patient population is definitively set forth in the references of record. The fact the dosage that was discussed in the Mercken reference was towards mice does not detract from the fact that it helps guide one of ordinary skill in the art to start looking at dosage translations for human administration. Further, applicant ignores the fact that the Qureshi reference, as set forth above, clearly teaches that Tau antibodies can be safely administered up to the 4200mg and that all of the dosages including 4200mg is well tolerated. Applicant argues that antibodies towards a different tau protein species cannot be used as a guide to the obtain the required dosage for the instantly claimed antibody. Applicant also argues that the limitation of claim calls for and IgG1 isotype and that the Qureshi reference teaches an IgG4 isotype and one of ordinary skill in the art would not considered switching from IgG4 to IgG1 due to its “… deleterious effects associated with IgG1 antibodies known in the art.” This is not found persuasive because Mercken teaches that their antibody is an IgG1 isotype and also teach that it is known in the art how to address the deleterious effects by modifying the Fc portion of these IgG1 antibodies. Further, this is not found persuasive because Mercken does teach the claimed antibody and sets forth a starting point for the possible effective dose. While the Qureshi reference teaches different tau antibodies towards a different part of the tau protein, or a different tau species as argued by the applicant, is still in the same field of endeavor and is an appropriate guide of where to start the dosage range for an anti-tau antibody treatment. These antibodies are targeting the same protein, tau, even if they have different epitopes which would be a great starting point for routine optimization of a dosage for antibody treatments against tau for one of ordinary skill in the art. The assertion that one of ordinary skill in the art would have had no expectation of success of using suggested dosages from different tau antibodies cannot be accepted since the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). There is no evidence of record that supports this assertion.
Applicant only argues that there are multiple Tau species and that different antibodies against epitopes of tau would not be predictable in determining the required doses of the claimed antibody to treat AD. Applicant argues that while the Mercken reference teaches a peripheral dose of 20mg/kg of the claimed antibody in a mouse model that this cannot determine if this would translate to a similarly effective dose for humans. This is not found persuasive because there is no evidence provided to support these statements of unpredictability. It is noted that it is common practice in the art to use animal models to do preliminary studies for specific treatments and used them as guideposts to determine the best starting points for dosages in human subjects. This clearly speaks to the fact that the art have used these animal models to make educated guesses on how to determine an optimal dose to start testing in human subjects. It is again pointed out the that dosage if not just guided by the Mercken reference but it is the combination of references, Mercken and Qureshi, obvious. Mercken also teaches the therapeutically effective amount of the treatment can be determined by those skilled in the art based on the consideration of several factors including the disease to be treated, the symptoms involved, patient’s body mass, etc. to extrapolate the effective doses based on a dose curve (see paragraph 94). Again, the Qureshi reference, as set forth above, clearly teaches that Tau antibodies can be safely administered up to the 4200mg and that all of the dosages including 4200mg is well tolerated. Therefore, this a clear teaching in the art that the same type of monoclonal tau antibodies can be administered in the claimed dose range, speaks to the fact that there is a reasonable expectation of success and motives one of ordinary skill in the art to try this dose range in the instantly claimed monoclonal tau antibody. Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. “Good science and useful contributions do not necessarily result in patentability.” PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342 (Fed. Cir. 2007). Therefore, the declaration fails to show how the prior art is unpredictable and unobvious.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
Applicant further argues that the limitation of the antibody having an IgG1 isotope would not motivate one of ordinary skill in the art, nor have an expectation of success, to combine the dosing in Qureshi et al., which discloses an IgG4antibody, with an IgG 1 antibody as set forth in instant claim 1, in light of the deleterious effects associated with IgG 1 antibodies known in the art. In addition, as described above, the instant invention unexpectedly exhibits both high potency and safety and tolerability that is associated only with the claimed dosing range, thereby demonstrating its criticality.
This is not found persuasive because Mercken teaches that the instantly claimed antibody B296 antibody is an IgG1 isotype and that the preferred immunoglobulin isotypes are IgG1, IgG2, IgG3 and IgG4 (see paragraphs 72, 136-141 and 267). Mercken acknowledges that there are considerations for the use of IgG1 and that these wildtype immunoglobulin can be modified depending of required effects.
See Mercken at paragraph 72:
“Antibodies of the invention include those that have
variations in their Fc region such that they have altered
properties as compared to wild type Fc regions including ,
but not limited to , extended half - life , reduced or increased
ADCC or CDC and silenced Fc effector functions . Antibody
light chains of any vertebrate species can be assigned to one
of two clearly distinct types , namely kappa and lambda ,
based on the amino acid sequences of their constant
domains . Accordingly , the antibodies of the invention can
contain a kappa or lambda light chain constant domain .
According to particular embodiments , the antibodies of the
invention include heavy and / or light chain constant regions
from mouse antibodies or human antibodies.”
Therefore, the art is well aware of the issue with all of the immunoglobulin isotypes an can easily modify these regions to account for the desired and undesired effects.
Finally, it is pointed out that the Shenoy reference is not dependent upon to teach the instantly claimed method, antibody or antibody dosage but rather it is depended upon to teach the claimed antibody composition.
The Dr. Van Kolen declaration under 37 CFR 1.132 filed 6/30/2025 is insufficient to overcome the rejection of claims 1, 3-9, 11-20 and 22 based upon Mercken et al., US2018/0265575 (2/15/2023 PTO-892) in view of Qureshi et al., 2018 (4/9/2024, PTO-892) and Shenoy US2018/0333493 (2/15/2023 PTO-892) under 35 U.S.C. 103 as set forth above in the Office action because: It include(s) statements which amount that the Mercken reference does not provide motivation or evidence of the instantly claimed dosage range (see statements 6-7). This is not found persuasive because this is not a 102 anticipatory rejection but rather a 103 obvious rejection.
In this case, Mercken teaches a method of treating tauopathies including AD, MCI due to AD, early AD, mild to moderate AD in a subject in need thereof including a human subject (see col.12, lines 22-23) using the same material (i.e. the same monoclonal anti-PHF-tau antibody) and the same active step (i.e. administering including intravenously administering to the human subject) in the same patient population (i.e. a human/patient suffering from AD, MCI due to AD, early AD, mild to moderate AD) (see the sequence alignment; col.4, lines 1-27; col. 4, line 49-col. 5, line 7; col. 5, lines 18-24; col. 12, line 63-col.13, line 14; col.14-17, tables 1-4; col.18, line 64-col.22, line 67; col. 30, line 1-col. 32, line 18; col. 32, line 22-41; col.32, lines 58-col.33, line 35; col. 39, lines 4-15, col. 51, line 1-col.53, line 67, Example 9; claims 31-39).
Mercken teaches treating a human subject having tauopathies including AD, MCI due to AD, early AD, mild to moderate AD (see col.12, lines 22-23) using an anti-PHF-tau monoclonal antibody having the same sequences recited in instant claims 1, 3-7 and the same active step and also teaches 20mg/kg per dose, which is within the claimed range of claims 1 and 12-17 (see col. 53, lines 12-17; col. 54, table 17; col. 27, lines 32-40). The motivation to try higher dosages are also supported by the Qureshi reference that is treating the same patient group with the same type of antibody treatment. Therefore, the combinations of references is what makes these dosages obvious to try and have a reasonable expectation of success. Therefore, the arguments are not found persuasive and the rejections are maintained.
The same arguments are presented towards to nonstatutory double patenting rejections and they are not found persuasive for the same reasons as discussed above.
Applicant's request that the provisional double patenting rejection of the instant claims over of the patent application be held in abeyance until there is allowable subject matter, at which time they will consider responding is not appropriate. Since applicant has not provided any objections or arguments for the provisional double patenting rejection of record, the above 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.
Advisory Information
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675