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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 04/23/2026 has been entered.
Response to Amendment
The amendment filed 04/23/2026, amending claim(s) 1 and 3 and newly adding claim 21 is acknowledged.
Newly submitted claim 21 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: In the response filed 3/11/2025 to the restriction requirement filed 9/11/2024, the Applicant elected Group 1, drawn to a red blood cell preparation for examination. Claim 21 reads on Group 4, drawn to a method for removing aggregated proteins, which was not elected for examination.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 21 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 1, 3-16, and 21 are pending.
Claims 1, 3, and 7 are pending and under examination.
Applicant’s amendments to the claims have overcome each and every claim objection and 112(a) rejection previously set forth in the Final Office Action mailed 10/23/2025.
Priority
Applicant's claim for the benefit of a prior-filed foreign application GB1904810.7 filed 04/05/2019 and PCT/BG2020/050900 filed 04/06/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Interpretation
Since the claims are directed to a preparation (i.e., product), the process language of the claims is evaluated to determine if the process imparts a structure or function not previously recited (i.e., if the process language is further limiting). Claim 1 recites “removing”, “separating”, and “recovering”, imparting the limitation that the claimed invention is a preparation of isolated cells. Isolating cells does not impart a structural change to the red blood cells of the claimed preparation. Claims 1 also recites “contacting the removed red blood cells ex vivo with an immobilized binding agent selected to specifically bind oligomeric or aggregated proteins associated with a protein aggregation disease”. However, the claims do not recite any modification of cells that result from the contacting and do not change the structure of the cells (e.g., characterizing the cells for a reduced level of the oligomeric or aggregated proteins is not the same as the cells being structurally modified, the recitation instead describes a functional characteristic of the cells). As such, the process does not impart any structural limitation.
The claimed red blood preparation is interpreted to read on a red blood cell population, with the functional characteristic of a reduced level of oligomeric or aggregated proteins.
See MPEP 2113 for further guidance on product-by-process claim evaluation.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The terms “reduced level” in claim 1 and “reduction” in claim 3 are relative terms which renders the claims indefinite. The terms “reduced level” and “reduction” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It’s unclear how an artisan would define and determine what a “reduced level” is.
If there are multiple ways to measure "reduced level", such as with different analytical method(s), yet each yields a different result, it is unclear which method is to be performed and which reference is to be used to determine infringement. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
Claim 1 recites “iii) separating the red blood cells from the immobilized binding agent with bound oligomeric or aggregated proteins; and v) recovering the separated red blood cells as the red blood cell preparation”. Claim 3 recites “the process further comprises analyzing the red blood cells after the separating step to confirm reduction of the oligomeric or aggregated proteins, and wherein the red blood cell preparation is recovered only after confirmation of the reduction.” It is unclear how an artisan would carry out the analyzing of claim 3, as the red blood cell preparation can be considered “recovered” already during the separating step of claim 1 (e.g., how does one differentiate separating the red blood cells versus recovering the red blood cells?). Once the cells are separated, are they not also then recovered? And in that case, has and artisan not already performed the recovery before analyzing? The examiner notes that as discussed above, the process by which the product is made is interpreted to not impart any structural limitations on the preparation, and the claimed red blood preparation is interpreted to read on a red blood cell population. As such, for examination purposes, claim 3 is interpreted to encompass the same limitations as claim 1.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iofrida et al. (Iofrida, C., et al. "Influence of physical exercise on β-amyloid, α-synuclein and tau accumulation: an in vitro model of oxidative stress in human red blood cells." Archives Italiennes de Biologie 155.1/2 (2017): 33-42.).
As discussed in the previous office actions (re-iterated below), the recitation of “wherein the red blood cell preparation is characterized by a reduced level of the oligomeric or aggregated proteins” is interpreted to not limit the structure or function of the cells in any way and is solely descriptive of the natural character of red blood cells and their protein levels.
Regarding claim 1, since the claims are directed to a composition (i.e., product), the process language of the claims is evaluated to determine if the process imparts a structure or function not previously recited (i.e., if the process language is further limiting). The additional elements do not limit the structure of the cells in any way and is solely descriptive of the natural character of red blood cells and their protein levels. As such, the process steps do not impart any structural limitation. Therefore, this recitation does not further limit the claimed invention. See further evaluation above under “Claim Interpretation”.
Iofrida et al. discloses comparing the content of Aβ (claim 7), α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) before and after in vitro oxidative stress treatment (i.e., red blood cell preparation has been treated ex vivo to reduce the level of oligomers or aggregates of proteins- although Iofrida et al. recites “in vitro” treatment, the disclosure of Iofrida et al. is interpreted to read on “ex vivo”, as the cells treated were derived from an organism and the cells were maintained outside their native organism; see ex vivo definition by Medical Dictionary). Total Aβ, α-syn and tau were quantified in RBCs (isolated from the subjects) by immunoenzymatic assays (i.e., an analytical method) (Abstract). Iofrida discloses that following oxidative stress, Aβ and α-syn content in RBCs were lower in the ATHL subgroup with respect to the SED one (Abstract).
Claim(s) 1, 3, and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stanley (WO2017/067672 A1, cited in Specification).
Stanley discloses detecting and analyzing structural forms of proteins in a biological sample as part of a process to diagnose a neurological disease. Specifically, Stanley discloses measuring total Abeta and total aggregated forms in whole blood in young normal controls and AD patients using ELISA (pg. 39, Example 9; pg. 41, Example 11). Additionally, levels of aggregated Abeta, alpha synuclein, and tau in whole blood from dementia and Parkinson’s Disease (PD) patients were also tested (pg. 42, Example 12). Table 6 shows that age matched controls had lower levels of Abeta, alpha-synuclein, and tau compared to AD, dementia, and PD patients. Further, Stanley discloses the use of protein solubilizing agents and chaotropic agents to displace, disrupt and solubilize all forms of Abeta from cell surfaces or protein complexes in the cellular fraction of blood (i.e., protein solubilization is the process of breaking interactions involved in protein aggregation- see BioRad). Stanley also discloses the use of beads derivatized with Protein A (GE Healthcare, magnetic Sepharose, diameter 50 μιη to 100 μιη) were coated with mouse monoclonal anti Abeta antibody in combination with protein solubilizing and disrupting reagents in order to immunocapture of all forms of the spiked protein (Abeta 1-42) in the blood matrix (i.e., collecting cells from an organism then treating is interpreted to read on ex vivo treatment) (pgs. 25-27, Example 1).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, and 7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s):
“A red blood cell preparation, obtained by a process comprising:
i) removing red blood cells from a subject or a donor;
ii) contacting the removed red blood cells ex vivo with an immobilized binding agent selected to specifically bind oligomeric or aggregated proteins associated with a protein aggregation disease;
iii) separating the red blood cells from the immobilized binding agent with bound oligomeric or aggregated proteins; and
iv) recovering the separated red blood cells as the red blood cell preparation,
wherein the red blood cell preparation is characterized by a reduced level of the oligomeric or aggregated proteins as a result of steps ii) and iii)”.
According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e., process, machine, manufacture, or composition of matter). Claims 1, 3, and 7 are drawn to a product comprising red blood cells, and products are compositions of matter. Thus, claims 1, 3, and 7 meet the requirements for step 1 analysis.
Second, the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019PEG, “directed to” is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application”, requires the presence
of an additional claim element(s) or a combination thereof to apply, rely on, or use the judicial
exception in a manner that imposes a meaningful limitation on the judicial exception, such that
the claim does not monopolize the judicial exception (See MPEP § 2106.05 for examples of
integration of practical application).
Regarding the first prong (1), claims 1, 3, and 7 are directed to a red blood cell preparation with a reduced level of oligomeric or aggregated proteins. Red blood cells are naturally occurring. The broadest reasonable interpretation “a reduced level of oligomeric or aggregated proteins” includes red blood cells that have a reduced level of oligomeric or aggregated proteins compared to the general population, or reduced over time in the subject or donor, with the reduction resulting from natural causes, such as a disease. As such, the claims encompass a red blood cells found in the body in nature. As such, the claims are drawn to a natural phenomenon and the first prong of the inquiry demonstrates that claims 1, 3, and 7 are directed to a judicial exception.
Regarding the second prong (2), claims 1, 3, and 7 recite the additional elements of “contacting”, “separating”, and “recovering”. These additional elements do not limit the structure or function of the cells in any way to a culture and is solely descriptive of how one main obtain the cells. Contacting the removed red blood cells ex vivo with an immobilized binding agent selected to specifically bind oligomeric or aggregated proteins does not modify the cells. Additionally, aggregated oligomeric or aggregated proteins may be cleared from red blood cells naturally in the body (e.g., see Ravi et al. 2005, which teaches the liver and spleen removing Abeta-fibrils from red blood cells,- e.g., pg. 34, col 2). Additionally, no other components are recited as part of the “preparation”. As such, no practical application is recited and therefore there is no integration into a practical application. Thus, claims 1, 3, and 7 meet the requirement of step 2A as being directed to a judicial exception.
Third, if a judicial exception is present in the claim, it is further assessed to determine if
the claims recite any additional elements or steps that are sufficient to ensure that the claim as
a whole amounts to significantly more than the judicial exception. As discussed above, the
additional elements recited in the claims are steps step (i.e., product-by-process) that do not further limit the natural phenomenon judicial exception. In addition, the steps do not impart any particular structural or functional limitation that further limits the generic nature of the natural phenomenon of red blood cells. Under the holding of Myriad, an isolated but otherwise unchanged nucleic acid was not patent eligible subject matter because it was not different enough from what exists in nature to avoid improperly tying up the future use and study of naturally occurring nucleic acid. The red blood cell preparation of the claims is analogous to the isolated nucleic acid in Myriad. The claimed red blood cell preparation can be interpreted as being an isolated red blood cell population that is otherwise unchanged. Thus, similar to the isolated nucleic acid, the isolated red blood cell preparation is not patent eligible subject matter because it is not different enough from red blood populations that exist in nature to avoid improperly tying up the future use and study of the naturally occurring red blood cell populations. As such, the additional elements do not impart any structural or functional elements that markedly transform or distinguish the judicial exception from its natural counterpart, as exemplified by Ravi et al. 2005.Thus, claims 1, 3, and 7 do not meet the requirement for step 2B of the analysis.
In conclusion, claims 1, 3, and 7 do not meet all the requirements of the 2019PEG subject matter patentability. Therefore, the claims are deemed patent ineligible.
Response to Arguments
Applicant's arguments filed 4/23/2026 have been fully considered but they are not persuasive. Regarding the 112(b) rejection of “reduced level” being a relative term that renders the claims indefinite, applicant argues that claim 1 have been amended to clarify the subject matter and that the claims should be free of this rejection. This argument is not persuasive because as discussed in the 112(b) rejection above, the amended claim language (i.e., adding the limitation of comparing levels to those prior to treatment) still does not address how an artisan would define and determine what a “reduced level” is.
Regarding the 102 rejection of claims 1, 3, and 7 as being anticipated by Iofrida et al., and as being anticipated by Stanley, the Applicant argues Iofrida et al. and Stanley do not disclose any ex vivo treatment of red blood cells or use of immobilized binding agents, separation, or recovery of red blood cells following affinity-based removal of oligomeric or aggregated proteins.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., affinity-based removal of oligomeric or aggregated proteins) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, the Applicant fails to distinctly point out why the cited references do not disclose an ex vivo treatment or respond to the Examiner’s evaluation of Iofrida et al. and Stanley disclosing an ex vivo treatment. Further, “immobilized binding agents” are not recited in the specification, and “binding agents” are not defined, only characterized by generic statements (e.g., “The ex vivo process can involve the use of compounds that reverse the aggregation status of oligomeric and aggregated proteins”) and examples (e.g., “Optionally the monomeric forms of the proteins that result from this treatment can be removed by an affinity adsorbtion step using a specific binding agent such as an antibody or a synthetic antibody such as an aptamer or a specific binding polymer prior to administering the further treated blood cell preparation to the subject. The monomers can also be separated from red cells using non-specific binding techniques such as ion-exchange or size exclusion chromatography.”), such as those found on pages 7-8.
Additionally, Stanley does disclose contacting red blood cells ex vivo (i.e., red blood cells removed from a subject) with an immobilized binding agent to selectively bind oligomeric or aggregated proteins (e.g., mouse monoclonal anti Abeta antibody beads).
Further, the Applicant fails to distinctly point out how the process by which the claimed red blood cell preparation is made imparts any structural limitations. What about the process by which the preparation is made would result in a red blood cell population structurally different from one found in the body, for example (e.g., as taught by Ravi et al.)?
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ALLISON MARIE JOHNSON/ Examiner, Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638
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