DETAILED ACTION
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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments, see Pg 8, filed 6/2/2026, with respect to the rejection(s) of the claim(s) under 35 U.S.C. 101 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amended claim set.
Applicant's arguments, see Pg 9-10, filed 6/2/2026, with respect to the rejection(s) of the claim(s) under 35 U.S.C. 102 have been fully considered but they are not persuasive.
Applicant’s position is Cao does not disclose, teach, or otherwise suggest the assembly mechanism, molecular interaction mode, and nanoparticle structure of the polypeptide albumin nanoparticle of claim 1.
This is not found persuasive as Cao does indeed teach the nanoparticle structure of claim 1, including the newly amended limitation wherein the size of the hydrated particle is 40-400nm; see art rejections below for more. Moreover, the assembly mechanism is an outcome of assembling components of opposite charge together and, therefore, by teaching the structural components of the albumin nanoparticle, Cao also inherently teaches the recited assembly mechanism and interaction mode; see Claim Interpretation section below. Thus, the claim rejections under 35 U.S.C. 102 have been maintained/modified below.
Applicant's arguments, see Pg 11, filed 6/2/2026, with respect to the rejection(s) of the claim(s) under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant’s position is that claim 1 is non-obvious over the combination of Ji and Cao because those references follow distinct technical routes and therefore a person of ordinary skill in the art would not combine them and a person skilled in the art has no reasonable motivation to introduce the tumor-killing small molecules into the delivery system.
Per MPEP 2143: The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art.
"[T]he analysis that "should be made explicit" refers not to the teachings in the prior art of a motivation to combine, but to the court’s analysis. . . . Under the flexible inquiry set forth by the Supreme Court, the district court therefore erred by failing to take account of ‘the inferences and creative steps,’ or even routine steps, that an inventor would employ and by failing to find a motivation to combine related pieces from the prior art." Ball Aerosol, 555 F.3d at 993, 89 USPQ2d at 1877.
Both Cao and Ji teach compounds designed to treat cancer. This is sufficient motivation for one skilled in the art to combine the claimed products into a singular product (also see MPEP 2144.06(I) - In re Kerkhoven – cited in art rejections below). Further, it provides a framework under which it would be obvious to try the specified combination of products in a singular method (MPEP 2143(I)E).
Applicant further posits that claim 1 is non-obvious over the combination of Hao and Cao by stating the deficiency of each individual reference.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As the deficiencies of Cao are remedied by Hao (or Ji, as described above) and there is motivation to combine them, the claim rejections under 35 U.S.C. 103 have been maintained/modified herein.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6 and 12, in the reply filed on 12/16/2025 is acknowledged. The traversal is on the ground(s) that unity of invention under 37 CFR 1.475(b)(3) is established. This is not found persuasive. Although unity of invention under 37 CFR 1.475(b)(3) does consist of a product, a process of use, and a method of making, the special technical feature that unites these inventions is not a special technical feature as it is anticipated by Xu and Yang (CN 110496229 A, published 11/26/2019). See prior Restriction Requirement.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of the species the cationic peptide of Formula I in the reply filed on 12/16/20254 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 1, 4-12 and 14 are pending. Claims 7-11 and 14 are withdrawn; claim 4 is hereby also withdrawn as a non-elected species claim based on amendment. Claims 1, 4-6, 8, 10, and 12 are currently amended.
Priority
This application is the 371 national stage entry of PCT/CN2021/128313, filed 11/3/2021, which claims priority to CN202111151600.4, filed 9/29/2021, and CN202011455391.8, filed 12/10/2020. The priority date of 12/10/2020 is acknowledged although no translation has been made of record.
Claim Interpretation
Claim 1 recites a polypeptide albumin nanoparticle is assembled from a cationic amphipathic polypeptide and serum albumin, wherein… the hydrophobic part of the cationic amphipathic polypeptide inserts into the serum albumin and the exposed positive charges from the polypeptide interact with negative charges on the surface of another serum albumin, thus promoting assembly of the polypeptide and the serum albumin into the nanoparticles, with the cationic amphipathic polypeptide embedded within the nanoparticle. The limitation “wherein… the hydrophobic part…” describes the functional outcome of placing the structural elements from the claim – a cationic amphipathic polypeptide and serum albumin – together, according to the instant specification (Pg 3, line 29 – Pg 4, line 6; also see instant Figure 1). As such, the claim is being interpreted based upon the structural limitations – a nanoparticle comprising a cationic amphipathic polypeptide and serum albumin – where the described molecular interactions are a functional outcome or consequence of combining the structural elements.
Claim Rejections - 35 USC § 112
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, 5, 6 and 12 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 recites the cationic amphipathic polypeptide comprise a hydrophobic part and a hydrophilic part at one end and a hydrophobic part at the other end (see lines 3-4). This limitation renders the scope of the claim indefinite as it is unclear whether the first and second recitations of “a hydrophobic part” in the claim are the same hydrophobic parts or two separate hydrophobic parts. For purposes of examination, the two hydrophobic parts will be interpreted as being the same hydrophobic part.
Moreover, claim 1 recites the limitation "the hydrophilic moiety" in lines 4-5. There is insufficient antecedent basis for these limitations in the claim as there is no prior recitation of a hydrophilic moiety, only a hydrophilic part.
By virtue of their dependency on claim 1, claims 5, 6 and 12 are also hereby rejected for this same reasoning.
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.
Claims 1, 6, and 12 are rejected under 35 U.S.C. 101 because they are directed to a judicial exception.
The Supreme Court has given a three-part test for patent eligibility (see flowchart of MPEP 2106(III)):
Are the claims drawn to a process, machine, manufacture, or composition of matter?
2a) If the claims pass the first test, are the claims drawn to a judicial exception (a law of nature, a natural phenomenon (product of nature), or an abstract idea)?
2b) If a judicial exception applies, do the claims recite additional elements that amount to significantly more than the judicial exception?
Applying the three-part test to the instant claims:
Regarding 1), the claims are drawn to a nanoparticle composed of a cationic amphipathic polypeptide and serum albumin, which is a composition of matter.
Regarding 2a), the nanoparticle claimed encompasses a product of nature.
Claim 1 recites a polypeptide albumin nanoparticle assembled from a cationic amphipathic polypeptide and a serum albumin, wherein the cationic amphipathic cationic polypeptide comprises a hydrophobic part and a hydrophilic part, wherein the hydrophilic part consists of 5-9 consecutive arginine or lysine residues, and the hydrophobic part comprises [Ir(ppy)2(H2O)2]OTf, a hydrophobic amino acid, a lipid, or combination thereof, wherein the nanoparticle forms as the cationic amphipathic polypeptide inserts into the serum albumin and the exposed positive charges interact with negative charges on the serum albumin, and hydrated has a particle size of 40-400nm. A cationic amphipathic polypeptide comprising a hydrophilic part consisting of 5-9 consecutive arginine and a hydrophobic part comprising a hydrophobic amino acid reads on the antimicrobial peptide Ubiquicidin (KVHGSLARAGKVRGQTPKVAKQEKKKKKTGRAKRRMQYNRRFVNVVPTFGKKKGPNANS; 5 consecutive arginine residues underlined, hydrophobic amino acids bolded), which is produced by leukocytes in humans, thereby reading on its occurrence and production in the bloodstream (see Table 1 of Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel). 2014 May 13;7(5):545-94.; and Pg 2, left column, “1.1. Ubiquicidin,” first and second paragraphs of Sachdeva et al. Ubiquicidin derived peptides for infection imaging. Nucl Med Biol. 2025 Jul-Aug;146-147:109049.). Because serum albumin is also found in human plasma, and the nanoparticles develop through a self-assembly mechanism, the claims read on this naturally-occurring product.
Regarding 2b), the do not recite features that amount to significantly more than the natural product; claim 6 reads on human serum albumin found in human plasma, and claim 12 reads on blood as a pharmaceutical composition. As such, they do not contain elements added to the judicial exception sufficient to render the claims significantly more than the exception.
Taken together, the claims are drawn to patent ineligible subject matter and are rejected here.
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.
(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, 6, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cao et al. (Albumin Biomimetic Nanocorona Improves Tumor Targeting and Penetration of Synergistic Therapy of Metastatic Breast Cancer. Adv. Funct. Mater. 2017, 27, 1605679.; cited on IDS filed 3/19/2025).
Cao teaches albumin biomimetic nanocorona (DRI-S@HSA) that can highly accumulate and penetrate tumor tissues, such as breast cancer (Abstract). Cao teaches that the nanocorona comprises a nine D-arginine (r9) cell penetrating peptide, linked to 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) via disulfide bonds to form an amphiphilic peptide derivative (r9-S-S-DOPE), camouflaged with human serum albumin (HSA, Pg 2, left column, third paragraph – right column, first paragraph; Figure 1). Cao further teaches that the size of the DRI-s@HSA nanocorona is ~60nm (Figure 1B), which is measured by DLS analysis and represents the nanocorona size in its hydrated states (Pg 3, right column, bottom paragraph; Pg 11, right column, “Preparation and Characterization of DRI-S@HSA,” first paragraph). Thus, claim 1 is anticipated.
Regarding claim 6, as stated above, the albumin is HSA.
Regarding claim 12, Cao describes the process by which the nanoparticles are generated in methanol and/or water and then dialyzed with water to remove methanol (Pg 11, left column, “Preparation and characterization of DRI” through “Preparation and characterization of DRI-S@HSA).
Claim Rejections - 35 USC § 103
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.
Rejections in view of Ji et al.
Claim(s) 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Cao et al. (Albumin Biomimetic Nanocorona Improves Tumor Targeting and Penetration of Synergistic Therapy of Metastatic Breast Cancer. Adv. Funct. Mater. 2017, 27, 1605679.; cited on IDS filed 3/19/2025) in view of Ji et al. (Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice. Chem Sci. 2020 Aug 10;11(34):9126-9133.; cited on IDS filed 3/19/2025).
The teachings of Cao have been set forth above. Cao does not teach that the cationic amphipathic polypeptide has a structural formula represented by Formula I.
Ji teaches compounds as part of a series of membrane active iridium(III) complexed oligoarginine peptides with a new cell death mechanism capable of overcoming drug resistance as well as stimulating immunological responses (Abstract). Ji teaches the following compound
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, where n is 3-8 (Figure 1). Complexing the oligoarginine peptides with 3-8 arginines with iridium(III) improved peptide retention time and cytotoxicity, as measured by IC50, with each additional arginine residue up to 8 further increasing the cytotoxicity (Figures 2 and 3).
Thus, regarding claim 5, Cao teaches albumin biomimetic nanocorona comprising the r9 CPP. Ji teaches iridium(III)-complexed oligoarginine peptides designed to treat cancer. Based on these teachings, it would be obvious to incorporate the Ir-oligoarginine peptide of Ji into the albumin biomimetic nanocorona of Cao. One skilled in the art would be motivated to do so in order to combine the therapeutic impacts of both Cao and Ji. One would have a reasonable expectation of success as Cao established that incorporation of the oligoarginine peptide r9 alone without iridium complexation could effectively treat cancer.
Additionally, per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). By extension of this, it would be obvious to combine the albumin biomimetic nanocorona of Cao and the anticancer iridium (III) complexed oligoarginine peptide of Ji into one compound because both are designed to effectively inhibit/kill cancer or tumor cells.
Rejections in view of Hao et al.
Claim(s) 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Cao et al. (Albumin Biomimetic Nanocorona Improves Tumor Targeting and Penetration of Synergistic Therapy of Metastatic Breast Cancer. Adv. Funct. Mater. 2017, 27, 1605679.; cited on IDS filed 3/19/2025) in view of Hao et al. (CN107129519A, published 9/5/2017).
The teachings of Cao have been set forth above. Cao does not teach that the cationic amphipathic polypeptide has a structural formula represented by Formula I.
Hao teaches a metal iridium complex-based polypeptide fluorescent cyclization method and polypeptide thereof (Abstract). Hao teaches that studies have shown that limiting the conformation of a linear polypeptide increases the affinity and selectivity for binding to its receptor and its performance in the cyclized state is significantly better than its linear state. Additionally, some methods of cyclizing linear peptides have drawbacks (Pg 2, “background technology”, second paragraph). To overcome these drawbacks, Hao teaches cyclizing a linear peptide through a metal-iridium complex-based polypeptide, which has the advantages of being a simple process, quick and easy to implement, low toxicity, and high stability (Pg 3, “summary of invention”, first paragraph).
Hao teaches the structure
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, wherein X1-Xn are amino acids and H is histidine (Figure 1). Hao teaches that the number of residues can be a positive integer greater than or equal to 0 (Pg 6, final paragraph – Pg 7, first paragraph).
Thus, regarding claim 5, Cao teaches albumin biomimetic nanocorona comprising the r9 CPP. Hao teaches a method to make cyclic peptides through metal iridium complexation; Hao further teaches that cyclized peptides show improvements over their linear counterparts, and the cyclization process through iridium complexation is easier and better for the aforementioned reasons compared to other cyclization methods. Based on these teachings, it would be obvious to incorporate the r9 peptide taught by Cao into the iridium complex taught by Hao. One skilled in the art would be motivated to do so in order to take advantages of the benefits of peptide cyclization taught by Hao. One would have a reasonable expectation of success as Cao indicated that r9 alone as a linear peptide without iridium complexation could be effectively used in nanocoronas to treat cancer and Hao established that the cyclization of linear peptides improved their activity.
Conclusion
No claim is allowed.
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 Sara Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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