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 .
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 1-2 have been amended and claim 21 has been newly added by Applicant’s amendment filed on 1/21/2026. Claims 1-21 are currently pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-9 in the reply filed on
11/19/2024 was previously acknowledged. Newly added claim 21 is incorporated into the elected group I for examination.
Claims 10-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected subject matter, there being no allowable generic or linking claim. This restriction was previously made final.
Examiner’s requirement for an election of species for “a single disclosed source from which the cellular membrane or hybrid membrane is derived” was previously withdrawn.
Therefore, claims 1-9 and newly added claim 21 are subject to examination to which the following grounds of rejection are applicable.
Priority
This application is a 371 of PCT/US2020/048906 filed 09/01/2020, which claims benefit to PRO 62/895,094 filed 09/03/2019.
Withdrawn Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 102
The rejection of Claims 1 and 3-4 under 35 USC § 102 is withdrawn in view of the amendments filed 1/21/2026.
Applicant’s arguments with regard to a withdrawn objection/rejection are moot.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claims 1 and 3-4 are newly rejected and claim 2 remains rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Gao M, Adv Mater. 2017, IDS; hereafter “Gao”) in view of Riess et al. (Riess JG. Artif Cells Blood Substit Immobil Biotechnol., 2005; hereafter “Riess”).
This rejection is modified in view of applicant’s claim amendments filed 1/21/2026.
Regarding Claims 1-2, Gao teaches a nanoparticle oxygen delivery vehicle (PFC@PLGA-RBCM) comprising a core that contains a perfluorocarbon (PFC) (Abstract). Specifically, Gao teaches, “The developed PFC@PLGA-RBCM nanoparticles with the PFC core show rather efficient loading of oxygen…” and “PFC@PLGA-RBCM nanoparticles are able to effectively deliver oxygen into tumors. The loading and delivery of oxygen by the nanoparticle of Gao anticipates the function of the nanoparticle (oxygen delivery vehicle) described in the instant application claim. Gao teaches the outer portion of the nanoparticle is coated by a cell-derived red blood cell membrane (Pg. 1, final sentence transitioning into Pg. 2). Gao teaches their nanoparticle to be 290nm (Pg. 3, Line 12; Figure 1C), which reads on the range recited in claim 1 of 100nm - 500nm.
Gao does not disclose the PFC of their invention to be perfluorooctyl bromide or other perfluoro halide as in instant claims 1 and 2.
Riess cures the deficiencies of Gao as Riess describes various characteristics of PFCs and further describes the characteristic of a stable, small-sized emulsion of a slightly lipophilic, rapidly excreted PFC, perfluorooctyl bromide (perflubron) (Abstract). Riess also teaches “F-octyl bromide offers the best combination of rapid excretion, ability to form stable emulsions with phospholipids and easy manufacture. Additionally, it has among the largest O2 and CO2 solubilities relative to its MW. F-octyl bromide has the advantage of being a totally synthetic material. Industrial access to perflubron is achieved via a simple bromination of a key intermediate,” (Pg. 58, 2nd full paragraph). Riess teaches that compared to other PFC candidates perflubron still stands out as the best candidate for O2 delivery (Pg. 63, 1st full paragraph).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have selected perfluorooctyl bromide (perflubron) as described by Reiss as the type of the PFC within the nanoparticle composition disclosed by Gao, particularly because Reiss teaches multiple advantages characteristics of perflubron, including describing it as the best combination of rapid excretion, ability to form stable emulsions with phospholipids and easy manufacture. Additionally, it has among the largest O2 and CO2 solubilities relative to its MW (Pg. 58, 2nd full paragraph).
Therefore, selection of a perfluorooctyl bromide (perflubron) as the type of PFC as described by Reiss into the nanoparticle of would predictably enhance the oxygen delivering utility therapeutic utility of the composition by leveraging the beneficial properties of perfluorooctyl bromide (perflubron)
There would be reasonable expectation of success to combine prior art elements according to known methods to yield predictable results.
Regarding Claim 3-4, Gao teaches the outer portion of the nanoparticle is coated by a cell-derived red blood cell membrane (Pg. 1, final sentence transitioning into Pg. 2).
Response to Applicants’ Arguments as they apply to the modified rejection of claim(s) 1, and 3-4 which are newly rejected and claims 3-9 which remains rejected under 35 U.S.C. 103
At pages 6-9 of the remarks filed on 1/21/2026, applicants essentially argue that the rejection of claims be withdrawn as there was no reason to combine the cited art. At pages 9-10 applicants essentially argue that superior and unexpected results rebut the rejections.
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These arguments have been fully considered but have not been found persuasive. At page 8, Applicant asserts the following (specific arguments provided for ease of reference):
Applicant then asserts that the obviousness rejection was based on improper hindsight.
With respect to the assertion that “Riess does not teach or suggest that its
nanoparticles made of perfluorooctyl bromide to be further modified in any way, let alone to be covered with "an outer surface comprising a cellular membrane or hybrid membrane derived from a cell" as recited in the present claim 1.”, Riess provides a design incentive in that the superior oxygen transport and stability that is taught would have motivated one of ordinary skill in the art to contemplate selecting Riess’s PFC for use in Gao’s system.
Further, there would be reasonable basis to conclude that modifying Gao’s system by selecting a PFC with functionally superior characteristics (such as taught by Riess) could be expected to yield predictable results.
With respect to the applicants’ assertion that “…the authors of Gao demonstrated, with experimental data, that its nanoparticles have the intended properties and can be used successfully to relieve tumor hypoxia and enhance cancer radiotherapy. (See e.g., Gao at Abstract and Figures 1-4.) As such, skilled artisans would not find any reason to motivation to further modify its nanoparticles…”, the fact that a system works does not preclude optimization.
A person having ordinary skill in the art at the time of the application would have been motivated to improve oxygen delivery and stability within a nanoparticle by selecting a potentially superior PFC such as perflubron as taught by Riess.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (Pg. 8 of remarks, final paragraph), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Further, it is well established in case law that a reference must be considered not only for what it expressly teaches, but also for what it fairly suggests. In re Burkel, 201 USPQ 67 (CCPA 1979). Furthermore, in the determination of obviousness, the state of the art as well as the level of skill of those in the art are important factors to be considered. The teaching of the cited references must be viewed in light of these factors.
At page 9, applicant argues the superior and unexpected properties of their invention rebut the obviousness allegations. Applicant provides the following in support of their argument:
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These arguments are not found persuasive. The evidence appears to be limited to a specific exemplary RBC-PFC nanoparticle and has not been shown to be commensurate in scope with the full breadth of claim 1, which is not limited to the specific tested formulation of the instant application, the specific use of RBC membrane outer surface, or specific oxygen carrying or stability performance. Moreover, the data provided is not sufficient to establish that the results would have been unexpected in comparison to the closest prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
Claim 5-6 remain rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Gao M, Adv Mater. 2017, IDS; hereafter “Gao”) in view of Riess et al. (Riess JG. Artif Cells Blood Substit Immobil Biotechnol., 2005; hereafter “Riess”) as applied to claims 1-4 above, and further in view of Zhang et al. (US 20130337066 A1, IDS; hereafter Zhang)
This rejection is modified in view of applicant’s claim amendments filed 1/21/2026.
Regarding Claims 5-6, The combined teachings of Gao and Riess render obvious the nanoparticle of claim 1 as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety.
Gao and Riess do not disclose the nanoparticle of their invention to comprise a releasable cargo or that the releasable cargo is a therapeutic agent, a prophylactic agent, a diagnostic or marker agent, a prognostic agent, or a combination thereof.
However, Zhang cures the deficiencies of Gao and Riess as Zhang discloses a nanoparticle with an outer surface derived from a cellular membrane, comprising a releasable cargo (Abstract; Paragraph [0010]) and discloses the releasable cargo may comprise one or more therapeutic agent, prophylactic agent, diagnostic or marker agent, prognostic agent, e.g., an imaging marker, or a combination thereof (Paragraph [0010]).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the combined teachings of Gao and Riess, to include within the nanoparticle composition a releasable cargo, such as a therapeutic agent, as disclosed by Zhang. Gao teaches that “cell-membrane-derived systems endow nanoparticles with functionalities that have been created and perfected by nature, so as to render unique properties to nanoparticles that can hardly be achieved with synthesized ones. For instance, it has been uncovered that nanoparticles coated with the membrane of red blood cells (RBCs) can preserve the membrane protein complexes that are essential for long blood circulation of RBCs, prolonging the blood half-lives of those membrane-coated nanoparticles.” (Pg. 1, final paragraph). Therefore, incorporating a therapeutic agent into a nanoparticle modified with a cell membrane would predictably enhance the therapeutic utility of the composition by leveraging the beneficial properties of the cell membrane outer coating.
There would be reasonable expectation of success to combine prior art elements according to known methods to yield predictable results.
Claims 7-8 remain rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Gao M, Adv Mater. 2017, IDS; hereafter “Gao”) in view of Riess et al. (Riess JG. Artif Cells Blood Substit Immobil Biotechnol., 2005; hereafter “Riess”) as applied to claims 1-4 above, and further in view of Lapek et al. (Lapek JD Jr., ACS Nano. (2017), IDS)
This rejection is modified in view of applicant’s claim amendments filed 1/21/2026.
Regarding Claim 7-8, The combined teachings of Gao and Riess render obvious the nanoparticle of claims 1 and 3 as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety.
Gao and Reiss do not disclose wherein the cellular membrane or hybrid membrane comprises a membrane derived from a white blood cell or specifically a macrophage.
Lapek cures these deficiencies as Lapek teaches a cellular membrane or hybrid membrane that comprises a membrane derived from a white blood cell. Specifically, Lapek discloses a nanosponge comprising a macrophage membrane (Abstract; Pg. 11831, column 2, 2nd paragraph; Pg. 11832, column 1, 3rd paragraph). Further, Lapek teaches the use of macrophage derived membranes allow for streamlining identification of known virulence factors and notably identifying numerous proteins of unknown function with high affinity for specific cell types (Lapek; Pg. 11835, column 1, 2nd paragraph).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the combined teachings of Gao and Riess, to include within the nanoparticle composition a membrane derived from a macrophage as disclosed by Lapek to obtain a nanoparticle with the characteristics that would increase the efficiency of specific application such as, macrophage membranes for streamlining identification of known virulence factors and notably identifying numerous proteins of unknown function with high affinity for specific cell types (Lapek; Pg. 11835, column 1, 2nd paragraph).
There would be reasonable expectation of success to combine prior art elements according to known methods to yield predictable results.
Claim 9 remains rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Gao M, Adv Mater. 2017, IDS; hereafter “Gao”) in view of Riess et al. (Riess JG. Artif Cells Blood Substit Immobil Biotechnol., 2005; hereafter “Riess”) as applied to claims 1-4 above, and further in view of Wang et al. (Wang H et al., J Nanobiotechnology (2019), IDS; hereafter Wang)
This rejection is modified in view of applicant’s claim amendments filed 1/21/2026.
Regarding Claim 9, The combined teachings of Gao and Riess render obvious the nanoparticle of claims 1 and 3 as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety.
Gao and Reiss do not teach a hybrid membrane derived from a platelet.
However, Wang cures this deficiency as Wang teaches a hybrid membrane derived from a platelet. Specifically, Wang teaches using a nanoparticle to encapsulate the anti-cancer drug bufalin and surrounded by a cell membrane derived from a platelet membrane (Abstract; Pg.4, 3rd- 4th Paragraphs). Wang also teaches the beneficial characteristics of a platelet derived membrane with a nanoparticle as they pertain to a cancer drug delivery system, “…expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells.”(Abstract). Additionally, Wang teaches the nanoparticles comprised of platelet derived membrane to have the capacity to mimic interfaces present in nature and completely vitiate recognition as a foreign body and subsequent immune response (Pg. 1, column 2, 1st Paragraph; Pg. 2, column 1, 2nd Paragraph).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the nanoparticle composition taught by Gao and Reiss to also include a hybrid membrane derived from a platelet as taught by Wang to obtain a nanoparticle with the characteristics that would increase efficiency of the nanoparticle to be used as a drug delivery system. Specifically, the addition of a platelet derived hybrid membrane would reduce immune response resulting in increased in vivo retention.
There would be reasonable expectation of success to combine prior art elements according to known methods to yield predictable results.
Response to Applicants’ Arguments as they apply to the modified rejection of claim(s) 5-9 under 35 U.S.C. 103
Regarding the rejection of claims 5-9, applicant essentially argues that Gao does not teach the amended claim 1 and the additional references of Zang, Lapek, and Wang respectively do not cure this deficiencies.
The combined teachings of Gao and Reiss render obvious claims 1-4. The combined teaching of Gao, Reiss, and Zhang render obvious the instant claims 5-6. The combined teaching of Gao, Reiss, and Lapek render obvious the instant claims 7-8. The combined teaching of Gao, Reiss, and Wang render obvious the instant claims 9.
In summary, applicants’ arguments have not been found persuasive. As discussed above, Gao teaches PFC-containing nanoparticles for use in oxygen delivery towards tumor hypoxia. Riess teaches that perfluorooctyl bromide/perflubron is a known PFC with advantageous oxygen carrier characteristics related to oxygen delivery and stability. Thus, it would have been obvious to one having ordinary skill in the art at the time of the instant application to select perfluorooctyl bromide as taught by Riess for inclusion in Gao’s nanoparticle system in order to obtain the known advantages taught by Riess.
Accordingly, the combination of Gao and Riess render the claimed nanoparticle obvious and the claims remain rejected.
New rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 21 is newly rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Gao M, Adv Mater. 2017, IDS; hereafter “Gao”) in view of Riess et al. (Riess JG. Artif Cells Blood Substit Immobil Biotechnol., 2005; hereafter “Riess”) as applied to claims 1-4 above, and as evidenced by Hoshyar et al. (Hoshyar N et al., Nanomedicine, 2016).
This is a new rejection necessitated by amendment of the claims in the response filed on 1/21/2026
The combined teachings of Gao and Riess render obvious the nanoparticle of claims 1 and 3 as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety. Regarding Claim 21, Gao teaches their nanoparticle size to be 290nm. Gao does not teach a nanoparticle size of 150-200nm as recited in instant claim 21.
However, nanoparticle size was well established as a result effective variable at the time of the instant application as evidenced by Hoshyar et al. Hoshyar et al. describes the effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction (Title) and specifically teaches “As nanoparticle size increases, the vascular permeability decreases. The pore size of tumor vesicles varies based on tumor type and growth location.” And further teaches that nanoparticle size impacts the tumor permeability (Pg. 680-681, Tumor permeability section).
A person of ordinary skill in the art would have been motivated to determine an appropriate size for a therapeutic nanoparticle through routine optimization in order to effectively produce a nanoparticle optimized for oxygen delivery to tumor.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Conclusion
Claims 1-9 and 21 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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