DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/27/2026 has been entered.
3. Applicant’s amendment to the claims filed on 03/27/2026 in response to the Final Rejection mailed on 10/29/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. Claims 2, 20-21, and 25 are cancelled.
5. New claim 27 is added.
6. Claims 1, 3, 8, 10-19, 22-24, and 26-27 are pending.
7. Claim 8 stands withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks filed on 03/27/2026 in response to the Final Rejection mailed on 10/29/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Information Disclosure Statement
7. The IDS filed on 03/27/2026 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claims 1-3 and 10-26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative term “rich” is withdrawn in view of applicants’ amendment to the claims to remove the recited limitation.
Claim Rejections - 35 USC § 112(a)
9. The written description rejection of claims 1-3 and 10-26 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants’ amendment to the claims, persuasive remarks, and cancellation of claims 2, 20-21, and 25.
Claim Rejections - 35 USC § 103
10. The rejection of claims 1-3, 10-18, 20-23 and 25 under 35 U.S.C. 103 as being unpatentable over Auty et al. (WO 2014/140023 A1; cited on IDS filed on 10/08/2021) in view of Villaverde et al. (EP 2476441 A1, 2012; cited on IDS filed on 10/08/2021) is withdrawn in view of applicants’ amendment to the claims to incorporate the limitations of claim 19 wherein the salt is Zn2+.
11. The rejection of claims 19, 24, and 26 under 35 U.S.C. 103 as being unpatentable over Auty et al. (WO 2014/140023 A1; cited on IDS filed on 10/08/2021) in view of Villaverde et al. (EP 2476441 A1, 2012; cited on IDS filed on 10/08/2021) as applied to claims 1-3, 10-18, 20-23, and 25 above, and further in view of Kho et al. (Biochemical and Biophysical Research Communications, 2000; cited on PTO-892 mailed 10/29/2025) is withdrawn in favor of the new rejection set forth below, which is necessitated by applicants’ amendment to the claims.
12. Claims 1, 3, 10-19, 22-24, and 26-27 are newly rejected under 35 U.S.C. 103 as being unpatentable over Auty et al. (WO 2014/140023 A1; cited on IDS filed on 10/08/2021) in view of Villaverde et al. (EP 2476441 A1, 2012; cited on IDS filed on 10/08/2021) and Kho et al. (Biochemical and Biophysical Research Communications, 2000; cited on PTO-892 mailed 10/29/2025). This new grounds of rejection is necessitated by applicants’ amendment to the claims.
With respect to claims 1 and 16, Auty et al. teach a protein nanoparticle comprising a cluster of one or more types of assembled self-contained protein and one or more salts of divalent cations in a concentration of 0.1 M to 10M, which is interpreted as encompassing the claimed ratio, and having a size from 100 nm to 10 mm [see Abstract; p. 2-3; p. 5 bottom top of p. 6].
Regarding the limitations, “which is a cell-free manufactured…” in claim 1 and “obtained by a method…”, these limitations are product by process limitations, and MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”. Nevertheless, Auty et al. teach the assembly of the nano- or microparticle by mixing in a solvent and divalent cations [see p. 5-6].
Regarding the limitations, is mechanically stable, which means that the cluster of self-contained proteins remains structured when submitted at sonication conditions including 5 rounds of 40 seconds; 0.5 of pulse on; 0.5 of pulse off and wave width of 10% in a high intensity sonicator Brnason sonifier 450, with 3 mm diameter titanium probe; is in the form of a precipitated pellet in aqueous media, when centrifuged at 15.000 g at a temperature from 4oC to 30oC; and it releases an amount of assembled self contained proteins lower than 50% by weight in relation to the total weight of assembled self-contained protein within 24 hours and when resuspended in an aqueous media at physiological temperature, it is acknowledged that Auty et al. does not explicit teach these limitations; however, the teachings of Auty et al. meet the structural limitations as required by the claim. As such, the examiner is of the position that these features are inherent to the nanoparticles taught by Auty et al. Since the Office does not have the facilities for examining and comparing applicants’ protein nanoparticle with the protein nanoparticle of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein nanoparticle of the prior art does not possess the same material structural and functional characteristics of the claimed protein nanoparticle). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 2, Auty et al. teach the protein nanoparticle wherein the divalent cation is calcium or magnesium [see bottom of p. 5].
With respect to claim 3, Auty et al. teach the protein nanoparticle is a fat substitute for food and beverages, which can broadly and reasonably be interpreted as a therapeutic protein [see p. 7].
With respect to claims 10-13, it is acknowledged that Auty et al. does not expressly disclose for use in the treatment of a disease. However, the recitation of "for use in the treatment of a disease" in the preamble of claim 10 merely recites the purpose of the protein and does not limit the body of the claims, while the limitations of "cluster of one or more one or more types of assembled self-contained protein, and one or more salts of divalent cations…" fully and intrinsically set forth all of the limitations of the claimed invention. See MPEP 2111.02.II. Claims 12-13 only further limit the intended use as defined by claim 10.
With respect to claim 14, Auty et al. teach the protein nanoparticle is a fat substitute for food and beverages comprising divalent metal cations, which can broadly and reasonably be interpreted as a therapeutically effective amount of a pharmaceutical composition and a pharmaceutically acceptable excipient [see Abstract; p. 2-3; p. 5 bottom top of p. 6; p. 7].
Regarding claim 15, it is acknowledged that Auty et al. does not expressly disclose which is for subcutaneous administration. However, the recitation of "for subcutaneous administration" in the preamble of claim 15 merely recites the purpose of the protein and does not limit the body of the claims, while the limitations of "cluster of one or more one or more types of assembled self-contained protein, and one or more salts of divalent cations…” and “pharmaceutically acceptable excipients or carriers" fully and intrinsically set forth all of the limitations of the claimed invention. See MPEP 2111.02.II.
With respect to claims 19, 26 and 27, Auty et al. teach a protein nanoparticle comprising a cluster of one or more types of assembled self-contained protein and one or more salts of divalent cations in a concentration of 0.1 M to 10M, which is interpreted as encompassing the claimed ratio, and having a size from 100 nm to 10 mm [see Abstract; p. 2-3; p. 5 bottom top of p. 6]. Auty et al. teach the protein nanoparticle wherein the divalent cation is calcium or magnesium [see bottom of p. 5].
With respect to claims 20 and 25, Auty et al. teach the protein nanoparticle wherein the divalent cation is calcium or magnesium [see bottom of p. 5] and one or more salts of divalent cations in a concentration of 0.1 M to 10M, which is interpreted as encompassing the claimed ration, and having a size from 100 nm to 10 mm [see Abstract; p. 2-3; p. 5 bottom top of p. 6].
However, Auty et al. does not teach the protein nano- or microparticle of claims 1 and 16 comprising one or more salts of Zn2+ and at least one region comprising three or more amino acids that dues to the presence of charge at physiological pH and/or the presence of aromatic or heteroaromatic structures can coordinate with the Zn2+; the protein nano- or microparticle of claims 17 and 22 wherein the proteins comprise at least three histidine amino acids; and the protein nano- or microparticle of claims 18, 23, and 26-27 wherein the proteins comprise a polyhistidine tag.
Villaverde et al. teach protein-lipid nano- or microparticles comprising T22-GFP-H6, V1-GFP-H6, vCCL2-GFP-H6, and CXCL12-GFP-H6 (interpreted rich in heteroaromatic amino acids and polyhistidine tags) in combination with lipids such as acyl chains (fatty acids), glycerophospholipids, sterols, or sphingolipids that self assemble into nanoparticles for therapeutic purposes and pharmaceutical purposes for the treatment of cancers such as colorectal cancers and subcutaneous administration [see Abstract; paragraphs 0024; 0077-0080; 0101; 0121].
Kho et al. teach that histidine is a chelator of zinc and can serve as nucleation centers for Zinc sulfide nanocrystal growth [see Abstract; p. 29].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Auty et al., Villaverde et al. and Kho et al. to use the divalent cation Zn to form the protein-lipid nano- or microparticles of Auty et al. because Auty et al. teach the formation of stabilized protein nanoparticles using divalent cation metals and Villaverde et al. teach nano- or microparticles comprising histidine rich proteins such as T22-GFP-H6, V1-GFP-H6, vCCL2-GFP-H6, and CXCL12-GFP-H6 for delivery to cells for treatment of diseases. Kho et al. teach that histidine is a chelator of zinc and can serve as a nucleation center for nanocrystal growth. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Auty et al., Villaverde et al. and Kho et al. because Villaverde et al. acknowledges that lipids can be combined with self-containing proteins to produce therapeutic protein nanoparticles for cell delivery, and Kho et al. acknowledges that zinc-histidine can serve as nucleation centers for nanocrystal growth. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
13. Applicants’ remarks filed on 03/27/2026 have been fully considered by the examiner. Beginning on p. 10 of applicants’ remarks, applicants in summary contend that the cited references fail to describe at least the feature of Zn2+, and Kho’s ratio is outside the scope of claim 1.
This argument is found to be not persuasive for the reasons set forth above and below. Briefly, Auty et al. discloses divalent cation salt ratios that encompass the claimed ranges in the claims. It would only require routine skill for one of ordinary skill in the art to apply similar concentrations to Zn2+ as this cation is an obvious variant of the cation salts disclosed in Auty et al.
Beginning on p. 11 of applicants’ remarks, applicants in summary contend that one of ordinary skill in the art would have had no motivation to substitute calcium for foodstuff in Auty with ZnS semiconductor nanocrystal of Kho et al. Furthermore, applicants contend that the range of Auty encompasses is extremely large and cannot render the recited range ratios obvious.
These arguments are found to be not persuasive because the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, one of ordinary skill in the art would recognize the interchangeability of the different divalent cations and their ability to form nanoparticles and would understand that Zn2+ could be used for similar purposes depending on the application. Furthermore, Auty et al. explicitly teach that the concentration of the salt is variable and depends on the type of salt, the type and concentration of protein and polysaccharide solution, and the processing conditions. Accordingly, Auty et al. contemplates that these variables can be modified depending on the application.
Beginning on p. 12 of applicants’ remarks, applicants contend that a person of ordinary skill in the art would have had a no reasonable expectation of success because the T22-GFP-H6 microparticle aggregates act as dynamic depots of functional proteins that deliver the proteins gradually through a precise tumor targeting via T22-CXCR4 interaction that achieve an unexpected effect that could not be predicted by the cited art.
This argument is found to be not persuasive because the argument of unexpected results must be commensurate in scope with the claimed invention. MPEP 716.02(d) states “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the instant case, the alleged unexpected property occurs with a T22-GFP-H6 microparticle; however, the claims are unlimited with respect to the type of protein in the nano- or microparticle. There is no evidence that the alleged property would occur with all proteins as encompassed by the claims.
Conclusion
14. Status of the claims:
Claims 1, 3, 8, 10-19, 22-24, and 26-27 are pending.
Claim 8 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 1, 3, 10-19, 22-24 and 26-27 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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