DETAILED ACTION
Applicants’ arguments, filed 10 February 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Note Regarding Claims 10-11
The examiner notes that claims 10-11 have been listed as “withdrawn” as of the claim status identifier. However, the text of the claims has not been included, which would appear to support the idea that these claims are cancelled.
For the purposes of examination under prior art, the examiner will proceed with the understanding that claims 10-11 have been withdrawn from consideration.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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 1-9 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.
Claim 1, step (i) recites the phrase “wherein the predetermined number of cells collected from each cell line represents from 0.25 to 4 parts of the total number of cells used.” It is unclear how this phrase further limits the claimed invention. This is at least because the term “parts” is unclear because it is unclear as to what the term “parts” is being compared. For example, it is unclear if a formulation comprising 0.25 parts of the first cell line with respect to 1 part of the first and second cell lines, but only 0.1 parts of the first cell line with respect to 1 part of the combination of the first cell line, second cell line, and therapeutic or diagnostic ingredient would meet the claimed requirement.
For the purposes of examination under prior art, the examiner will examine the claims as if the text “wherein the predetermined number of cells collected from each cell line represents from 0.25 to 4 parts of the total number of cells used” does not further limit the claim.
Response to Arguments Regarding Indefiniteness Rejection
Applicant has provided arguments regarding the previously applied indefiniteness rejection, as of applicant’s response on 10 February 2026 (hereafter referred to as applicant’s response). These arguments are addressed below.
As an initial matter, the examiner notes that the previously applied indefiniteness rejection addressed two separate issues related to the previously presented claim limitation “so that the corresponding predetermined number of cells collected from each cell line represents from 0.25 to 4 parts of the total number of cells collected.” The claim amendments set forth on 10 February 2026 appear to solve the first issue presented by the examiner but do not solve the second issue presented by the examiner. These arguments are addressed in more detail below.
Applicant makes the following arguments as of pages 5-6, relevant text reproduced below.
As amended, the quantitative limitation is now expressly tied to the cell collection step, at a stage where the number of cells collected from each cell line is determinable and meaningful.
The examiner does not dispute the position taken in the above-reproduced text. As such, this particular issue has been solved in view of the claim amendment. However, the issue discussed in the above-reproduced text is not the only reason that the claims were previously rejected as indefinite in the prior office action.
Applicant further presents the following arguments.
The amendment also clarifies that the term "parts" defines the proportion of cells from each source cell line relative to the total number of cells used, consistent with the description in the specification explaining that membrane quantities are determined based on the number of source cells.
The examiner disagrees that the term “parts” has been clarified to define the proportion of cells from each source relative to the total number of cells used. This is because the scope of claim 1 includes four parts of one cell. According to the above-reproduced definition, this would mean that there are four times the amount of one cell as the total number of cells, which is a mathematical impossibility. As such, applicant’s arguments fail to overcome the above-indicated indefiniteness issue.
Claim Rejections - 35 USC § 103 – Obviousness
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3 and 6-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Biomaterials, Vol. 192, 2019, pages 292-308 and S-1 to S-29) in view of Posch (“Proteomic Profiling” Humana Press, 2015, pages i-xv and 1-501).
Jiang et al. (hereafter referred to as Jiang) is drawn to lipid particles made by the fusion of red blood cell membrane together with the membrane of the MCF-7 cell line, as of Jiang, page 292, title and abstract. See Jiang, page 294, Scheme 1, reproduced below.
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The examiner notes that this figure, when presented in its original color, shows red membrane derived from the red blood cell and blue membrane derived from the MCF-7 cell, as of Jiang, page 294, title and abstract. The benefits of combining these together are taught by Jiang, page 293, left column, bottom paragraph, relevant text reproduced below, and include long circulation time from the red blood cell membrane and tumor targeting from the MCF-7 membrane.
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As to claim 1, step (i), Jiang teaches providing red blood cells, as of Jiang, page S-2, section 1.1, and separately teaches providing MCF-7 cells, as of Jiang, pages S-2 and S-3, section 1.2.
As to claim 1, step (ii), Jiang teaches lysing the red blood cells with hypotonic solutions to form cell ghosts, as of Jiang, page S-2, section 1.1. Jiang also teaches removing the nucleus of the MCF-7 cells via homogenization, as of Jiang, page S-3, section 1.2, second through fourth lines.
As to claim 1, step (iii), Jiang teaches extracting red blood cell membranes as of page S-2, section 1.1, and teaches extracting MCF-7 membranes as of page S-3, section 1.2.
As to claim 1, step (iv), Jiang teaches the following on page S-4, section 1.3, relevant text reproduced below.
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The above-reproduced text discloses mixing red blood cell membranes, MCF-7 membranes, and melanin nanoparticles, which are a therapeutic agent because they treat cancer by photothermal therapy, as of Jiang, page 292, title.
Jiang does not teach that homogenization occurs at 80 to 167 psi, as required by step (v) of claim 1. The examiner notes that atmospheric pressure is about 14.7 psi; as such, the pressures taught by Jiang exceed atmospheric pressure.
Posch is a book entitled “Proteomic Profiling.” Posch teaches various methods for homogenizing cells as of chapter 1 of Posch, starting on page 1 of Posch. Posch teaches a method for homogenizing cells at 10-250 psi, as of Posch, page 16, section 8, relevant text reproduced below.
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It would have been prima facie obvious for one of ordinary skill in the art to have subjected the cell membranes of Jiang to the method of Posch. Jiang is drawn to providing cell membranes and homogenizing said membranes to form nanoparticles. Posch teaches that cell materials can be homogenized by subjecting said cells to pressures in the range of 10-250 psi. As such, the skilled artisan would have been motivated to have subjected the cell materials of Jiang to pressures in the range taught by Posch in order to have predictably homogenized said cell membranes with a reasonable expectation of success.
As to claim 1, step (v), Jiang teaches homogenizing red blood cell and MCF-7 material together, as of Jiang, page S-4, section 1.3, relevant text reproduced above. The skilled artisan would have been motivated to have used a pressure ranging from 80-167 psi in view of the teachings of Posch. This pressure overlaps with the claimed pressure. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Also as to claim 1, step (v), the claim requires 6 to 14 passages. Jiang appears to teach one passage through three filters on page S-4; however, this process appears to result in only three passages rather than six passages. The skilled artisan would have been motivated to have increased the number of passages in order to have predictably caused more homogenization and to have predictably removed more unhomogenized material with a reasonable expectation of success. The particles formed from this step would have met the requirement of being cell-membrane derived nanoparticles because of the combination of a membrane derived from red blood cells and MCF-7 membrane.
As to claim 1, step (vi), Jiang teaches isolating the final product through centrifugation as of page S-4, section 1.3. The particles formed from this step would have met the requirement of being cell-membrane derived nanoparticles because of the combination of a membrane derived from red blood cells and MCF-7 membrane.
As to claim 2, the teachings of Posch on page 16, section 8, reproduced above, would appear to indicate that the process of using gas pressure in the range of 10-250 psi would appear to be useful for cell lysis as well as size reduction of the material produced therefrom. As such, the skilled artisan would have been motivated to have used the method of Posch to have conducted lysis. The skilled artisan would have been motivated to have repeated steps in order to have more completely conducted the lysis process.
As to claim 3, Jiang teaches lysis of the MCF-7 cells with a homogenizer on page S-3, third line.
As to claim 6, the red blood cells of Jiang were taken from drawing blood from mice, as of Jiang, page S-2, section 1.1, and are therefore understood to read on the required primary cell line. The MCF-7 of Jiang is understood to read on the required immortalized cell line.
As to claim 7, the melanin nanoparticles of Jiang are understood to read on the required anti-cancer agents since they kill cancer cells via the photothermal effect.
As to claim 8, the melanin nanoparticles of Jiang appear to generate strong photoacoustic contrast, as of Jiang, page 303, section 3.4.
As to claim 9, Jiang discusses an embodiment comprising doxorubicin, as of Jiang, page 297, right column. Doxorubicin is an anti-cancer therapeutic agent which has a molecular weight of 543 Daltons.
Claims 4 and 5 – No Prior Art Rejection
The examiner has not rejected claims 4-5 as anticipated or obvious prior art. The examiner presents the following rationale explaining the examiner’s decision not to reject these claims over prior art.
Claim 4 further limits claim 1 by reciting a centrifugation step utilizing a 100 kDa centrifugal filter in order to obtain the cell membrane dispersion from the cell lysate. The claim recites collecting and retaining the non-filtered fraction; as best understood by the examiner, this step recites the retention of material with a molecular weight lower than about 100 kDa and the removal of material with a molecular weight higher than about 100 kDa.
In view of this, the examiner conducted a search regarding the membrane proteins present in both red blood cells and MCF-7 cells, which are the cell types taught by Jiang. Briefly, the results of this search indicated that both red blood cells and MCF-7 cells comprise proteins with a molecular weight exceeding 100 kDa.
Regarding red blood cells, the examiner cites Aoki (Membranes, Vol. 7(56), 2017, pages 1-19), which is drawn to red blood cell membrane glycoproteins, as of Aoki, page 1, title and abstract. Aoki teaches the following, as of table 1 on page 2, reproduced below.
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The above-reproduced text lists ten separate membrane proteins in red blood cell membranes, with three of ten having molecular weights well above 100 kDa (namely spectrin-α, spectrin-β, and ankylin) and another one of ten having a molecular weight of 100 kDa (AE1).
The skilled artisan would have expected that had Jiang been modified such that a 100 kDa centrifugal filter been applied and the filtrate collected, the spectrin-α, spectrin-β, and ankylin would have been removed from the red blood cell membrane sample for having a molecular weight exceeding 100 kDa. There would have been no motivation for the skilled artisan to have removed spectrin-α, spectrin-β, and ankylin from the red blood cell membrane sample of Jiang. As such, the skilled artisan would not have been motivated to have modified Jiang to have included the use of a 100 kDa membrane filter in the method of Jiang.
In a similar vein, the skilled artisan would have expected MCF-7 cell membrane to have included proteins with a molecular weight higher than 100 kDa. In support of this position, the examiner cites Powell et al. (Journal of Steroid Biochemistry and Molecular Biology, Vol. 77, 2001, pages 97-108). Powell et al. (hereafter referred to as Powell) teaches 110 kDa and 130 kDa membrane proteins in MCF-7 cells, as of Powell, page 97, abstract, relevant text reproduced below.
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The examiner understands “130 k” to refer to 130 kDa, and “110 k” to refer to 110 kDa molecular weight proteins.
The Western blot on page 101 of Powell also appears to show significant proteins exceeding 100 kDa, as of Powell, page 101, left column, figure 2, reproduced below.
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The above-reproduced text and figures show the presence of proteins with a molecular weight exceeding 100 kDa. The skilled artisan would have expected that had Jiang been modified such that a 100 kDa centrifugal filter been applied and the filtrate collected, the proteins with a molecular weight of 100 kDa would have been removed from the MCF-7 membrane sample. There would have been no motivation for the skilled artisan to have said high molecular weight proteins from the MCF-y membrane sample of Jiang. As such, the skilled artisan would not have been motivated to have modified Jiang to have included the use of a 100 kDa membrane filter in the method of Jiang.
Response to Arguments Regarding Prior Art Rejections
Applicant has provided arguments regarding the previously applied obviousness rejection, as of applicant’s response on 10 February 2026 (hereafter referred to as applicant’s response). These arguments are addressed below.
Applicant makes the following arguments on page 6, relevant text reproduced below.
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These arguments continue onto the paragraph bridging pages 6-7, which is reproduced in part below.
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The examiner does not dispute the facts described by the above-reproduced text. However, to the extent that applicant is arguing that the instant claims exclude the melanin nanoparticles of Jiang, the examiner disputes that position. Melanin nanoparticles are used for photothermal therapy against cancer, as of Jiang, page 292, title and abstract. The melanin nanoparticles also appear to be diagnostic agents by generating photoacoustic contrast, as of Jiang, page 303, section 3.4. This is explained in greater detail in the rejection of claims 7-8 above as well as on page 12 of the prior office action mailed on 20 November 2025. As such, the examiner understands the melanin nanoparticle of Jiang to be both a diagnostic agent as well as a therapeutic agent.
Applicant then makes the following argument, as of page 7, third paragraph, relevant text reproduced below.
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This is not persuasive because the instant claims do not exclude the presence of pre-formed nanoparticles such as the melanin nanoparticles of Jiang. As such, applicant appears to be arguing subject matter not actually recited by the instant claims. Such arguments are not persuasive; see MPEP 2145(VI).
Applicant makes arguments regarding Jiang’s use of extrusion rather than high pressure homogenization, as of applicant’s response, page 8, second paragraph, relevant text reproduced in part below.
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As best understood by the examiner, applicant appears to be arguing that extrusion is necessary in Jiang due to the use of melanin nanoparticles as the bioactive agent. Applicant may also be arguing that had Jiang been modified to use high pressure homogenization instead of extrusion, the resultant method would not have been successful because high pressure homogenization would not have successfully formed the nanoparticles of Jiang. This is not persuasive because the position taken by applicant that high pressure homogenization would not have successfully formed the nanoparticles of Jiang appears to be a position that requires evidence; in contrast, applicant merely presented argument in support of this position. Attorney arguments cannot take the place of evidence; see MPEP 716.01(c)(II) and MPEP 2145(I). With that being said, if, purely en arguendo, applicant was to present evidence (e.g. in the form of an affidavit or declaration) showing that the skilled artisan would have expected failure had the extrusion of Jiang been replaced with high pressure homogenization, such evidence could potentially overcome the applied rejection on the grounds that a proposed modification cannot render the prior art unsatisfactory for its intended purpose, as per MPEP 2143.01(V).
Regarding the Posch reference, applicant argues that the droplet nebulization taught by Posch differs from the required high-pressure homogenization, as of applicant’s response, bottom half of page 8 and top of page 9. This is not persuasive. Posch teaches pressures as high as 250 psi, as of Posch, page 16, section 8, relevant text reproduced on page 10 of the prior office action mailed on 20 November 2025. Posch also teaches sufficient shearing forces to break cells, which indicates that homogenization is occurring. As such, the examiner understands the method of Posch to be high-pressure homogenization.
Applicant then refers to the method of Posch as a low-pressure method, as of applicant’s response, page 9, top paragraph. This is not persuasive because Posch teaches pressures as high as 250 psi. The pressure range of Posch of 10 to 250 psi overlaps with the claimed pressure range of 80 to 167 psi. As such, the pressure taught by Posch would not appear to be other than high pressure.
Applicant makes the following arguments regarding the number of passages, as of applicant’s response, page 9, relevant text reproduced below.
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In this argument, applicant appears to argue that the passages in the instant application are to achieve membrane fusion, whereas the passages in Jiang are for a different purpose. However, this is not persuasive. This is because the passages in Jiang are to achieve membrane fusion. See the following text reproduced below from Jiang, page 294, right column, bottom paragraph.
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As such, it appears that the purpose of the passages both in Jiang as well as in the claimed invention is to achieve membrane fusion.
Applicant makes arguments regarding alleged impermissible hindsight reasoning, as of applicant’s response, paragraph bridging pages 9-10. This is not persuasive. Any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper. See MPEP 2145(X)(A). In this case, the examiner did not use knowledge gleaned from the disclosure in setting forth the applied rejection. As such, applicant’s arguments related to alleged impermissible hindsight are not persuasive.
Suggested Amendment to Claim 1 to Overcome Prior Art Rejection
The examiner has provided the following proposed amendment of claim 1. The examiner clarifies that the proposed amendment is intended only to overcome the currently applied prior art rejection and not the indefiniteness rejection. It should not be construed as placing the claims in condition for allowance. See the next page for the test of claim 1 with the proposed amendment.
Claim 1 (Suggestion): Method for the production of cell-membrane derived nanoparticles comprising the steps of:
I) providing from two to four cell cultures, each cell culture being of a different cell line, and collecting a predetermined number of cells from each cell line; wherein the predetermined number of cells collected from each cell line represents from 0.25 to 4 parts of the total number of cells used.
II) lysing the predetermined number of cells of each cell line to obtain lysates of each cell line;
III) extracting cell membranes from the lysate of each cell line to obtain cell membrane dispersions of each cell line;
IV) mixing the cell membrane dispersion of each cell line and adding an aqueous solution or dispersion containing a therapeutic or diagnostic ingredient to obtain a mix dispersion;
V) homogenising the mix dispersion at an external air pressure ranging from 80 to 167 psi, with a number of passages ranging from 6 to 14, to form a dispersion containing a plurality of cell-membrane derived nanoparticles;
VI) isolating the plurality of the cell-membrane derived nanoparticles from the dispersion containing them,
wherein the inner core of the cell-membrane derived nanoparticles is made of an aqueous solution containing the therapeutic or diagnostic ingredient.
Reasons for Providing This Suggestion: The examiner’s reasons for providing the applied suggestion are because the composition made by the method of Jiang has an inner core that is the melanin nanoparticle, which appears to lack an aqueous solution. As such, the proposed amendment excludes the case in which the inner core is other than an aqueous solution. Therefore, the proposed new claim text causes the claim to exclude the case wherein the inner core is a nanoparticle such as the melanin nanoparticle of Jiang, thereby overcoming the currently applied prior art rejection.
The proposed new claim text is adequately supported in the manner required by 35 U.S.C. 112(a) as of the instant specification on page 15 lines 8-9.
The examiner clarifies that this proposed amendment is intended only to overcome the previously applied prior art rejection. It does not overcome the previously applied indefiniteness rejection and should not be construed as necessarily placing the claims in condition for allowance.
Conclusion
No claim is 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 ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612