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
Continued Examination under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on October 22, 2025 and amendment after final filed on October 22, 2025 has been entered. Claim 3 was canceled, claims 1, 4-8, 12-13 were amended, claim 15 was newly added and claims 1-2, 4-15 are pending in the instant application.
The restriction requirement was deemed proper and made FINAL in a previous office action.
Claims 1-2 and 4-15 are examined on the merits of this office action.
Withdrawn Rejections
The rejection of claims 3-5, 6-10, 12-13 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed October 22, 2025.
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, 4-15 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 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 14), 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 of reducing beta amyloid, and in particular, Aβ1-42 which inherently be achieved. Nevertheless, the ability of Albutein (albumin) to bind Aβ42 is well known and shown in Boada (see Table 1).
Regarding new 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 “As set forth above, Claim 1 has been amended and now recites, among others, "selecting a patient suffering from moderate AD", and Claim 15 reciting "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" has been added. The recited step of selecting a patient suffering from moderate AD is neither disclosed nor suggested by Boada. For this reason, Boada cannot anticipate presently pending independent Claim 1 or any of its dependent claims. As such, withdrawal of the rejection under 35 U.S.C. § 102(a)(1) is respectfully requested.
Moreover, the recited selection of a patient suffering from moderate AD yields represents a nonobvious improvement over the prior art. Making this selection in the context of the presently claimed invention yields entirely unexpected results, as illustrated in Figures 11B - 11C. As explained on page 3, lines 28-30 of the specification as filed, Figure 11B is a graph illustrating the levels of Aβ₁-₄₂ in CSF of patients with mild AD after combined treatment with TPE and LVPE and Figure 11C shows levels of Aß₁-4₂ in CSF of patients with moderate AD after such combined treatment. As can be seen in Figure 11B, after treatment with both TPE and LVPE (i.e., the bars on right side of illustration), levels of Aß1-42 in CSF of patients with mild AD was essentially unchanged compared to untreated controls. In contrast, Figure 11C shows a substantial decrease in levels of Aβ₁-₄₂ in CSF of patients with moderate AD after treatment with both TPE and LVPE. In other words, the present inventors unexpectedly discovered that combined treatment of TPE and LVPE produced a substantial decrease in Aß1-42 levels only in the case of moderate AD population and not in the case of mild AD. Additional unexpected results obtained by the claimed invention are also shown in Figs 6- 9 of the present application in which results of cognitive tests were administered. In this regard, the specification as originally filed states at page 8, lines 13-17 that "as shown in Figure 6 and 7, treated patients with mild AD were compared with the control group. A change from baseline of 1.1 and 0.7 of ADAS-Cog and ADCS-ADL, respectively, was observed. However, as shown in Figure 8 and 9, change from baseline of ADAS-Cog and ADCS-ADL in treated patients with moderate AD (MMSE 18-21) was of 3.9 and 8.6, respectively. This is a very surprising result, as it suggests that better results can be obtained in more advance stages of AD." Boada provides no suggestion of the recited selection of a patient with moderate AD. Indeed, without knowledge of the inventors' discovery that treatment with a combination of TPE and LVPE would provide a reduction in Aß1-42 levels only in a population suffering from moderate Alzheimer's Disease, a person having ordinary skill in the art would have no reason to carry out such a selection step. Indeed, the disclosure of Boada is of an ongoing clinical trial that has not yet been completed. Thus, one having ordinary skill in the art could not have drawn any conclusions concerning the types of patients for which the treatment might be successfully employed.
Applicant’s arguments have been fully considered but not found persuasive. Boada expressly discloses treating mild to moderate Alzheimer’s disease. A patient population comprising “mild to moderate” Alzheimer’s disease necessarily includes patients suffering from moderate Alzheimer’s disease. A reference that disclose treatment of a patient population that includes the claimed subgroup anticipates a claim directed to that subgroup when the subgroup is expressly encompassed. Boada does not exclude moderate AD, rather is affirmatively includes it. Accordingly, Boada discloses treating patients suffering from moderate AD, and thus inherently discloses selecting such patients for treatment.
With respect to claim 15, Boada’s disclosure of treating “mild to moderate AD” constitutes a group including mild and moderate AD. Selection of moderate AD patients from that group is therefore expressly encompassed by Boada. Thus, the limitation of “selecting a patient suffering from moderate AD” does not distinguish over Boada.
Applicant’s arguments regarding unexpected results are not persuasive because the present rejection is under 35 U.S.C. 102, not 103. Evidence of unexpected results may be relevant to rebut a prima facie case of obviousness under 35 U.S.C. 103. However, where a prior art reference discloses each and every limitation of the claimed invention, evidence of unexpected results cannot overcome anticipation.
Boada discloses the identical treatment protocol applied to the identical patient population (mild to moderate AD), including moderate AD patients. Where the same method is performed on the same patient population, the discovery of a previously unappreciated result does not render the method patentable. Moreover, the claims are not limited to any magnitude of reduction or comparative efficacy related to mild AD patients. The claims merely recite reduction of beta-amyloid protein in a patient suffering from moderate AD. Because Boada performs the same treatment steps on moderate AD patients using albumin known to bind Ab1-42, reduction of beta amyloid would necessarily an inevitably occur.
Applicant’s argument that Boada was an ongoing clinical trial is not persuasive. Anticipation does not require that a prior art reference demonstrate completed clinical conclusions or statistically significant outcomes. Rather, anticipation requires disclosure of the claimed method. Boada discloses treatment of mold to moderate AD patients comprising an initial TPE phase (4-6 weeks); a maintenance LVPE phase (monthly); use of 5-20% albumin an administration of IVIG in alternation with albumin. These are the same steps recited in the pending claims. Whether the study had reached final clinical conclusions is not material to whether the method was disclosed.
Regarding Applicant’s arguments that because claim 1 is patentable, dependent claims are patentable. Applicant’s arguments have been fully considered but not persuasive. Because independent claim 1 is anticipated by Boada, the dependent claims, which incorporate all the limitations of claim 1 and add further limitations also disclosed by Boada, remain anticipated for the reasons previously set for in the office action.
Furthermore, because Boada performs the identical plasma exchange protocol on moderate AD patients using albumin known to bind AB1-42, reduction of beta amyloid would necessarily and inevitably result.
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, 4-15 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) 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 “Presently pending Claim 1 of U.S. App. No. 18/557,828 recites "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." Thus, 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 is to treat patients having moderate Alzheimer's Disease, which represents an MMSE of 18-21. 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.”
Applicants arguments have been fully considered but not found persuasive. The MMSE greater than equal 15 limitation of the copending application expressly encompasses patients having MMSE scores of 18-21. Thus, the presently claimed moderate AD patient population is fully contained within the patient population recited in the copending claims. Selecting a subpopulation within an overlapping or encompassed range does not render the claims patentably distinct absent evidence of criticality or a materially different invention. No such distinction is established here. Both applications recite materially the same therapeutic regimen of TPE and LVPE using human albumin at overlapping concentrations for treatment of Alzheimer’s disease. Accordingly, the differences relied upon by Applicant do not render the
claims patentably distinct, and the provisional nonstatutory obviousness type double patenting rejection is maintained.
New Objection
Claim 5 is being objected to for the following informality: the limitation “wherein said TPE is conducted at least during 6 weeks” should be replaced with -conducted for at least 6 weeks- or -conducted over a period of at least 6 weeks-.
Claim 12 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 11. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654