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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on June 3, 2026 is acknowledged. Claim 1 was amended, claims 3, 14 were canceled and claims 1-2, 4-13 and 15 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 1-2, 4-13 and 15 are examined on the merits of this office action.
Maintained/Revised Rejections
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 4-13, 15 are/remain rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Boada (Neurologia, 2016:31(7) pages 473-481, cited in Applicant’s IDS).
Boada discloses a method of treating mild to moderate Alzheimer’s comprising administering low volume plasma exchange (see page 478, right column last paragraph “Ambar Study”, page 479, left column second paragraph, lines 9-10). Boada teaches a method of using apheresis (Therapeutic plasma exchange, TPE) and haemapheresis low volume plasma exchange with albumin and replacement IVIG at three different doses (see page 479, left column, first four lines). Regarding claim 1, Boada teaches first TPE is carried prior to VLPE (see page 479, left column, “The AMBAR study includes a first stage of intensive treatment followed by a second stage of maintenance treatment. The initial intensive treatment lasts 6 weeks with one session of therapeutic apheresis per week: 2.5-3 L of plasma are extracted and replaced with the same volume of Albutein® 5%). Regarding the newly amended limitation of “selecting a patient suffering from moderate AD having a MMSE score of 18-21”, Boada discloses enrolling patients having MMSE scores between 18-26 (see Boada, supplement, patients section, “Mini mental state Examination (MMSE) scores between greater than equal to 18 and less than equal to 26”). This disclosed patient population encompasses patients having MMSE scores of 18-21, corresponding to moderate Alzheimer’s disease. Accordingly, Boada discloses the claimed patient selection limitation. Regarding the newly amended limitation “wherein a reduction in AB1-42 is observed in CSF from patients suffering from moderate AD, whereas said reduction in AB1-42 is not observed in CSF from patients suffering from mild AD treated under the same protocol”, he limitation merely recites a biological property or result associated with performance of the otherwise identical treatment method disclosed by Boada. The claim does not recite any affirmative active step of measuring CSF AB1-42 levels, comparing biomarker levels between mild and moderate Alzheimer’s disease patients, or modifying the treatment protocol based on such measurements. Rather, the claim recites the biological response associated with practicing the disclosed treatment protocol.
Boada teaches administering the same TPE/LVPE treatment protocol to Alzheimer’s disease patients having MMSE scores encompassing the claimed moderate AD subgroup. The absence of an express disclosure in Boada comparing CSF AB1-42 levels between mild and moderate Alzheimer’s disease patients does not demonstrate that the recite biological characteristic is absent from the prior art method. The claimed limitation does not distinguish the claimed method from the otherwise identical treatment protocol disclosed by Boada.
Regarding claims 1-2, Boada teaches LVPE treatment monthly for 12 months (see page 479, left column, “Next, haemapheresis, considered maintenance treatment, is performed for 12 months. It consists of therapeutic apheresis of a low monthly volume of plasma (650—800 mL approximately) which is replaced by Albutein 20% (a maximum of 100 mL or 200 mL)”). The 20% Albumin meets the limitations of 5-25% of instant claim 1.
Regarding claims 4-5, Boada teaches TPE is once per week (see page 479, left column, second paragraph , “The initial intensive treatment lasts 6 weeks with one session of therapeutic apheresis per week: 2.5—3 L of plasma are extracted and replaced with the same volume of Albutein® 5%”).
Regarding claims 6-8, Boada teaches 1 LVPE treatment every month (30 days in between) for 12 months meeting the limitations of instant claims 6-8, which a total amount of 12 rounds of LVPE.
Regarding claim 9, Boada teaches wherein 20% albumin in 100-200 mL meets the limitations of 20-40 grams of human albumin (see page 479, left column, “It consists of therapeutic apheresis of a low monthly volume of plasma (650—800 mL approximately) which is replaced by Albutein® 20% (a maximum of 100 mL or 200 mL).
Regarding claim 10, Boada teaches wherein 20% albumin in 100-200 mL meets the limitations of 20-40 grams of human albumin(see page 479, left column, “It consists of therapeutic apheresis of a low monthly volume of plasma (650—800 mL approximately) which is replaced by Albutein® 20% (a maximum of 100 mL or 200 mL).
Regarding claims 11-13, Boada teaches administering IGIV (see page 479, first paragraph, lines 1-4, second paragraph, lines 13-15). Regarding claim 13, Boada teaches use of the immunoglobulins in alternate to albumin and thus meeting the limitations of not a the same time.
Regarding the limitation of “wherein said TPE and LVPE reduces the level of the beta amyloid protein in the patient” (claim 1) and in particular Aβ1-42 (claim 1), Boada teaches the same method of the instant claims including treating the same patient population, moderate Alzheimer’s disease, same method steps, utilizing TPE and LVPE with the same concentration of human albumin, and thus, the result oriented effect recited in the claim is a property associated with practicing the disclosed treatment method and does not impose any additional affirmative treatment step beyond the method already disclosed by Boada. Nevertheless, the ability of Albutein (albumin) to bind Aβ42 is well known and shown in Boada (see Table 1).
Regarding claim 15 and the limitation of “selecting a patient suffering from moderate AD” in claim 1, Boada discloses treating patients suffering from mild to moderate Alzheimer’s disease. A patient population described as “mild to moderate” necessarily constitutes a group including both mild and moderate Alzheimer’s disease patients. Because Boada performs the disclosed treatment protocol on this group, moderate AD patients are necessarily selected from that group for treatment. Therefore, the limitation that “said selection of the patient suffering from moderate AD is a selection from a group of the patients including moderate and mild Alzheimer’s disease” is expressly or inherently disclosed by Boada.
Response to Applicant’s Arguments
Applicant argues that Boada does not distinguish between patients suffering from mild Alzheimer’s disease and moderate Alzheimer’s disease and therefore fails to disclose the amended limitations of claim 1 requiring selecting a patient suffering from moderate Alzheimer’s disease having MMSE score of 18-21 and subjecting the selected patient to the claimed treatment protocol wherein a reduction in AB1-42 is observed in CSF from patients suffering from moderate Alzheimer’s disease, whereas such reduction is not observed in CSF from patients suffering from mild Alzheimer’s disease treated under the same protocol. Applicant further argues that the specification demonstrates that the claimed reduction in CSF AB1-42 levels occurs in moderate Alzheimer’s disease patients but not in mild Alzheimer’s disease patients and that such results are unexpected and not disclosed or suggested by Boada. Applicant additionally argues that Boada reports no significant difference in CSF AB1-42 levels between treatment groups and therefore does not anticipated the instant claims.
Applicant’s arguments have been fully considered but not found persuasive. Regarding the limitation of “selecting a patient suffering from moderate AD having a MMSE score of 18-21”, Boada expressly teaches enrolling patients having MMSE scores between 18 and 26. See Boada, patients section. The disclosed MMSE range encompasses patients having MMSE scores of 18-21, corresponding to the claimed moderate Alzheimer’s disease subgroup. Accordingly, Boada expressly discloses the claimed patient selection limitation. Regarding the limitation “wherein a reduction in AB1-42 is observed in CSF from patients suffering from moderate AD, whereas said reduction in AB1-42 is not observed in CSF from patients suffering from mild AD treated under the same protocol”, the claim does not recite any affirmative method step requiring measurement of CSF AB1-42 levels, comparison of biomarker levels between patient populations, or modification of the treatment protocol based upon such measurements. Rather, the limitation recites a biological characteristic or property associated with performance of the otherwise identical treatment method.
Boada teaches administering the same therapeutic plasma exchange (TPE) and low volume plasma exchange (LVPE) treatment protocol to patients having MMSE scores encompassing the claimed moderate Alzheimer’s disease subgroup. The absence of an express discussion in Boada regarding subgroup specific biomarker analyses does not demonstrate that the recited biological characteristic is absent from the disclosed method. Applicant has not established that patients within the disclosed MMSE range of 18-21 treated according to Boada’s protocol would necessarily fail to possess the recited biological characteristic. Applicant’s reliance on the specification as evidence of allegedly unexpected results is not persuasive with respect to the present rejection under 35 U.S.C. 102. Whether the claimed biological response may be unexpected does not negate anticipation where the prior art teaches the identical treatment protocol administered to a patient population expressly encompassing the claimed subgroup. Applicant further argues that Boada reports no statistically significant difference in CSF AB1-42 levels between treatment groups. However, the cited disclosure reports aggregate study results and does not separately analyze patients according to disease severity. The absence of an express subgroup analysis does not establish that the claimed biological characteristic is absent from patients treated according to the disclosed method within the claimed MMSE range. Take together, Applicant’s arguments have been considered but are not persuasive, and the rejection under 35 U.S.C. 102(a)(1) is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-2, 4-13, 15 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-17 of copending Application No. 18/557828 (reference application) in view of Boada(Neurologia, 2016:31(7) pages 473-481, cited in Applicant’s IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating moderate Alzheimer's Disease (AD) having a MMSE score of 18-21, by reducing a level of a beta-amyloid protein in a patient suffering from the moderate AD, comprising: selecting a patient suffering from moderate AD; and subjecting the selected patient suffering from moderate AD to therapeutic plasma exchange (TPE) followed by one or more rounds of low-volume plasma exchange (LVPE) using a composition comprising human albumin at a concentration between 5% (w/v) and 25% (w/v), wherein said TPE and LVPE reduces the level of the beta-amyloid protein in the patient”.
The instant application further claims two or more rounds of LVPE (claim 2); TPE weekly for six weeks (claims 4-5); two or more rounds of LVPE 30 days after a previous round of said two or more rounds of LVPE (claims 6-8); 10-40 grams of human albumin during LVPE (claims 9-10) and further administering IGIV but not at the same time as albumin (see claims 10-13), wherein the beta amyloid protein is AB1-42 and selecting a patient suffering from moderate AD from a group containing both mild and moderate.
Co-pending Application No. 18/557828 claims “A method for treatment of a cognitive impairment in a patient in need thereof, wherein said treatment comprises a combination of a treatment regime of conventional therapeutic plasma exchange (TPE), in which 2000 mL to 3000 mL of the patient's plasma is exchanged with a human albumin solution, and a treatment regime of low-volume plasma exchange (LVPE) in which 600 mL to 900 mL of the patient's plasma is exchanged with human albumin at a concentration of 5% (w/v) to 25% (w/v), and wherein said patient has a Mini Mental State Examination (MMSE) greater or equal to 15” (claim 1). Co-pending Application No. 18/557828 further claims before the treatment regime of LVPE previous rounds of TPE are carried out (claim 4); 1 TPE a week for 6 weeks (claims 5-6); TPE regime the plasma is replaced with albumin at a concentration between 4 % (w/v) and 6 % (w/v), preferably at 5 % (w/v) (claim 7); 1 LVPE a month for 12 months (claims 8-100; 20-50 g albumin with LVPE (clam 12); treating Alzheimer’s disease (claim 14). Co-pending Application No. 18/557828 is silent to alternating with immunoglobulins and treatment of moderate Alzheimer’s disease.
However, Boada (see reference/teachings above) teaches use of IVIG as an alternative to albumin with plasma exchange (see page 479, left column, first paragraph). Boada teaches treating mild and moderate Alzheimer’s patients (see abstract, last two lines, page 477, right column, lines 5-6, paragraph 0004, first two lines, Conclusions, last paragraph). It would have been obvious to try IVIG in place of or alternative to human albumin for plasma exchange and treatment of Alzheimer’s. One of ordinary skill in the art would have been motivated to do so given that immunoglobulins can be successfully used in plasma exchange in alternative to human albumin. Furthermore, it would have been obvious to treat both and mild and moderate Alzheimer’s. One of ordinary skill in the art would have been motivated to do so given Boada teaches treating mild and moderate Alzheimer’s disease with the same method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant argues that “the claims of U.S. App. No. 18/557,828 are to treat all patients having Mini Mental State Examination (MMSE) greater or equal to 15. In contrast, Claim 1 of the present application requires selection of patients having an MMSE of 18-21, i.e. moderate AD and not mild AD, leading to reduction in the level of the beta- amyloid protein in CSF only in patients suffering from moderate AD but this is not observed in patients suffering from mild AD treated under the same protocol. As discussed above, the selection of these patients represents a nonobvious improvement over the prior art. Accordingly, Applicant respectfully submits that the presently pending claims can be patentably distinguished as nonobvious from Claims 1 and 4-17 of U.S. App. No. 18/557,828 at least for the same reasons they are nonobvious over Boada. As such, Applicant respectfully requests reconsideration and withdrawal of the provisional obviousness-type double patenting rejection.
Applicant’s arguments have been fully considered but not found persuasive. The provisional nonstatutory obviousness type double patenting rejection is based on the combined teachings of the claims of co-pending Application no. 18/557828 in view of Boada. Accordingly, the issue is not whether the claims of the reference application alone expressly disclose the presently claimed subject matter, but whether the differences between the claims would have been obvious to one of ordinary skill in the art at the time of the invention. Regarding the limitation requiring that a reduction in CSF AB1-42 is observed in moderate Alzheimer’s disease patients but not in mild Alzheimer’s disease patients treated under the same protocol, Applicant has not demonstrated that the limitation defines a patentably distinct treatment method over the combination of the reference application and Boada. The claim does not recite any affirmative step of measuring CSF AB1-42 levels, comparing biomarker levels between patient populations, or modifying the treatment protocol based upon such measurements. Rather, the limitation recites a biological property or result associated with practicing the otherwise known treatment method.
Applicant’s reliance on allegedly unexpected results is likewise not persuasive. Although evidence of unexpected results may be considered in determining obviousness, the evidence must be commensurate in scope with the claims and sufficient to outweigh the strong evidence of obviousness presented by the combined teachings of the reference application and Boada. The evidence presented does not establish that the claimed treatment protocol itself differs from the combined teachings of the reference application and Boada, but instead attributes a newly recognized biological response to an otherwise known treatment regimen.
Accordingly, Applicant has not shown that the presently claimed subject matter is patentably distinct from claims 1, 4-17 of co pending Application No. 18/557828 in view of Boada. Therefore, the provisional nonstatutory obviousness type double patenting rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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