DETAILED ACTION
Receipt of Arguments/Remarks filed on November 6 2025 is acknowledged. Claims 6, 8-16, 18-21, 24-27, 30-34 and 36 were/stand cancelled. Claims 1 and 17 were amended. Claims 37-39 were added. Claims 1-5, 7, 17, 22-23, 28-29, 35 and 37-39 are pending. Claims 22-23, 28-29 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 14 2025. The examiner notes that claim 17 was previously withdrawn in light of the species election of biomolecule. However, since the restriction requirement of March 14 2025 did not specifically provide an option for electing a single biomolecule or a particular combination of biomolecules, claim 17 is no longer considered withdrawn, in light of the amendments filed November 6 2025 indicating the nanocomposite further comprising a second biomolecule which is clearly supported in paragraph 0017 of the instant specification.
Therefore, claims 1-5, 7, 17 and 37-39 are being examined on the merits herein.
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 .
New and Modified Rejections Necessitated by the
Amendments filed November 6 2025
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, 37 and 39 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 term “ “high molecular weight” in claims 1 and 39 is relative term which renders the claim indefinite. The term “high” is not defined by the claim, 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. While high and low molecular weight poly(I:C) is available from invivogen (see US20180243444A1) the instant specification does not teach the poly(I:C) used is from invivogen. Newly added claim 37 indicates that high molecular weight poly I:C comprises 1.5 kilobases-8 kilobases. Therefore, in order to be a proper dependent claim, the scope of claim 1 must be broader. But the specification never contemplates the scope of high molecular weight. Furthermore, the scope of the molecular weight in claim 37 is indefinite as the claim recites the high molecular weight poly I:C comprises 1.5 kilobases-8 kilobases. These means additional kilobases can be present as represented by the recitation comprises. Therefore, the scope of the high molecular weight is still indefinite.
Response to Arguments
Applicants’ arguments filed November 6 2025 have been fully considered but they are not persuasive.
Applicants argue that high molecular weight poly I:C are terms familiar to the skilled person in the art. It is argued that the InvivoGen Product specification sheets lists numerous references which demonstrate this product has been known for decades. Applicants argue that submitted paper (Appendix B) which was published by the inventors demonstrates that the HMW poly I:C was provided by InvivoGen.
Regarding Applicants’ arguments, firstly, the data sheet provided by InvivoGen indicates that a HMW poly I:C has a molecular weight of 1.5 to 8 kb. This is different than instant claim 37 which states the poly I:C comprises 1.5-8 kilobases. Secondly, in order for claim 37 to be a proper dependent the claim scope of the high molecular poly I:C in claim 1 has to be broader than the range recited in claim 37. Levy (US Patent No. 4349538) teaches a high molecular weight polyriboinosinic-polyribocytidylic acid (claim 1) which has a molecular weight in the range of 7 x 105 Daltons to about 1 x 107 Daltons (700,000 Daltons to 10,000,000 Daltons) (claim 2) which does not appear to the same as InvivoGen. While Applicants might argue that the instantly claimed poly I:C utilized is from invivogen, the instant specification doesn’t state this and evidence of such presented in a declaration was not submitted. The examiner directs applicant's attention to MPEP 716.02: The reason for requiring evidence in declaration or affidavit form is to obtain the assurances that any statements or representations made are correct, as provided by 35 U.S.C. 25 and 18 U.S.C. 1001. Since this information is critical to the scope of the invention, there must be evidence on the record in declaration or affidavit form to obtain the assurances that any statements are correct.
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 37 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 37 introduces new matter as the claims recite the limitation: "high molecular weight poly I:C comprises 1.5 kilobases-8 kilobases”. There is no support in the specification for this limitation. The limitation of: "poly I:C comprises 1.5 kilobases-8 kilobases" was not described in the specification as filed, and person skilled in the art would not recognize in the applicant’s disclosure a description of the invention as presently claimed. The specification discloses high molecular weight poly I:C but does not describe the instantly claimed limitation. There is no guidance in the specification to select a poly I:C comprising 1.5 to 8 kilobases and from MPEP 2163.06: “Applicant should therefore specifically point out the support for any amendments made to the disclosure.” Applicant has not directed the Examiner to the support in the specification for this particular amendment. The sections pointed to by applicants merely provide support for high molecular weight poly I:C. Therefore, it is the Examiner’s position that the disclosure does not reasonably convey that the inventor had possession of the subject matter of the amendment at the time of filing of the instant application.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-5, 7 and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Szigeti et al. (WO2012110835, cited on PTO Form 1449) in view of Pozuelo Rubio et al. (USPGPUB No. 20180243444) and Xue et al. (CN 108904803 A) as evidenced by Dow et al. (USPGPUB No. 20170281754).
Applicant Claims
The instant application claims a biofunctionalized nanocomposite, comprising:(a) a core comprising a nanoparticle formed of Prussian blue materials; (b) a shell obtained by partially or completely encapsulating the Prussian blue core with at least one biocompatible coating comprising citrate; and (c) at least one biomolecule attached to, or absorbed to, the biocompatible coating wherein the at least one biomolecule comprises a latency reversing agent (LRA) wherein the LRA comprises a high molecular weight polyinosine-polycytidylic acid (poly I:C).
As claimed the nanocomposite further comprises a second biocompatible coating comprising polyethylenimine (PEI).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Szigeti et al. is directed to Prussian blue (PB) based nanoparticle as multimodal imaging contrast material. Claimed is a Prussian blue based nanoparticle comprising a Prussian blue based metal core doped with one or more metal isotopes and an organic biocompatible coating (reading on shell) (claim 1). The Prussian blue has the formula AxM’m[M(CN)6]n wherein A can be K, M can be Fe, M’ can be Fe, m is 0 to 5, x is 0 to 5 and n is 0.5 to 10 (claim 2). The biocompatible coating comprises one or more biocompatible material such as polymers and citrate (claim 4). The nanoparticles can be used for therapy of different diseases or disorders such as mammary cancer (i.e. breast cancer) of all histological types (page 9). Example 1 shows Prussian with citric acid. The Prussian blue has formula Fe4[Fe(CN)6]3. The PB nanoparticles can also be used in imaging (example 11). The citric acid is taught as acidifying the PB nanoparticle. Other acids include HCl (page 7).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Szigeti et al. discloses the same Prussian blue core as claimed and a biocompatible coating comprising citrate which is the same as instantly claimed and suggests more than one biocompatible coating can be used and polymers can be used, Szigeti et al. does not teach PEI or a polyIC. However, these deficiencies are cured by Pozuelo Rubio et al. and Xue et al.
Pozuelo Rubio et al. is directed to novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine. The use of synthetic analogs of double-stranded RNA (dsRNA) that mimic viral dsRNA has been explored in recent years for specifically activating the immune system against tumors with the scope of inhibiting cancer cell growth and inducing cancer cell apoptosis. In particular, double-stranded polyinosinic-polycytidylic acid (named as poly(I:C) or pIC) has been characterized as a type of dsRNA with various effects of therapeutic interest against various cancers such as breast cancer (paragraph 0002). Unfortunately initial preclinical evidence shows naked poly(I:C) revealed its slow stability, poor homogeneity, unpredictable pharmacokinetics and limited antitumoral effects (paragraph 0003). The pitfalls that are limiting the clinical development of poly(I:C) molecules as a drug and its compliancy with regulatory requirements could be overcome by producing structurally complex anticancer complexes comprising poly(I:C) molecules together with drug delivery systems for cancer therapy that are often based on cationic polymers such as polyethyleneimine (PEI) (paragraph 0007). The poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight (paragraph 0296). Breast cancer is taught (paragraph 0224; 0234).
Xue et al. is directed to amine-modified preparation for carrying the Prussian blue magnetic nanoparticle of photosensitizer of polyethyleneimine (PEI). The particles have Prussian blue and a PEI coating which allows for a system with good biological compatibility for the treatment of breast cancer (abstract). The Prussian blue is acidified followed by coating with PEI (claim 1;5). The cationic polymer PEI is taught as being a bridge to other molecules such as a photosensitizer which can interact via electrostatic interaction (section 2, right before description).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 1, 4-5 and 7:
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Szigeti et al., Pozuelo Rubio et al. and Xue et al. and coat the Prussian blue nanoparticles of Szigeti et al. with the cationic polymer polyethyleneimine (PEI). One skilled in the art would have been motivated to coat the particle with PEI to allow for further functionalization as taught by Xue et al. Since the particles of Szigeti et al. are acidified with citric acid (i.e. negatively charged) and the PEI is cationic, one skilled in the art would have expected two layer coating on the nanoparticles would be formed. Furthermore, Xue et al. teaches coating after acidifying the Prussian blue nanoparticles. Therefore, there is a reasonable expectation of success in coating the nanoparticles of Szigeti et al. with the PEI.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Szigeti et al., Pozuelo Rubio et al. and Xue et al. and utilize the combination of PEI and poly (I:C) with the nanoparticles of Szigeti et al. Szigeti et al. teaches that the particles can be used for imaging or therapy for cancers such as breast cancer. Xue et al. confirms that Prussian blue nanoparticles with a PEI coating can also be used for treating breast cancer. Pozuelo Rubio et al. teaches a complex of poly (I:C) and PEI can be utilized in the treatment of breast cancer. One skilled in the art would have been motivated to combine Prussian blue with poly(I:C) as both are taught as being useful in the treatment of breast cancer. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Furthermore, the combination of Prussian blue with the poly(I:C) would allow for imaging of the cancer cells as well, an additional benefit. Pozuelo Rubio et al. teaches the poly(I:C) complexes with the PEI. Therefore, a coating of the PEI complexed with the poly(I:C) would result in the biomolecule being attached to, or absorbed to the biocompatible coating.
Regarding the claimed high molecular weight poly I:C and claim 37, Pozuelo Rubio et al. teaches the poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight. Therefore, it would have been obvious to utilize the commercial source of poly(I:C) taught by Pozuelo Rubio et al. As evidenced by Dow et al., poly I:C obtained from invivogen with a high molecular weight has an average size of 1.5-8 kb (paragraph 0074).
Regarding claims 2-3, Szigeti et al. exemplifies Fe4[Fe(CN)6]3 which is an iron hexacyanoferrate. The Prussian blue formula taught by Szigeti et al. overlaps in scope with instantly claimed general formula I.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02
Claims 17 and 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over Szigeti et al. in view of Parks et al. (Cell Reports, 2019) and Zhou et al. (Innate Immun. 2014) as evidenced by Scharf et al. (eLife, 2016) and Hafner et al. (Biomaterials, 2011).
Applicant Claims
The instant application claims the nanocomposite further comprises a second biomolecule attached to, or absorbed to, the biocompatible coating, wherein the second biomolecule comprises at least one broadly neutralizing antibody (bnAB) against human immunodeficiency virus (HIV), and wherein the at least one bnAB comprises 3BNC117, VRCO1, VRC02, or 10-1074.
The instant application claims a biofunctionalized nanocomposite, comprising:(a) a core comprising a nanoparticle formed of Prussian blue materials;(b) a shell obtained by partially or completely encapsulating the Prussian blue core with at least one biocompatible coating comprising citrate;(c) high molecular weight (HIIW) polyinosine-polycytidylic acid (poly I:C) attached to, or absorbed to, the biocompatible coating, and(d) at least one broadly neutralizing antibody (bnAB) against human immunodeficiency virus (HIV) attached to, or absorbed to, the biocompatible coating.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Szigeti et al. is directed to Prussian blue (PB) based nanoparticle as multimodal imaging contrast material. Claimed is a Prussian blue based nanoparticle comprising a Prussian blue based metal core doped with one or more metal isotopes and an organic biocompatible coating (reading on shell) (claim 1). The Prussian blue has the formula AxM’m[M(CN)6]n wherein A can be K, M can be Fe, M’ can be Fe, m is 0 to 5, x is 0 to 5 and n is 0.5 to 10 (claim 2). The biocompatible coating comprises one or more biocompatible material such as polymers and citrate (claim 4). The nanoparticles can be used for therapy of different diseases or disorders (page 9). The biocompatible material can be an antibody (claim 4; page 5). Example 1 shows Prussian with citric acid. The Prussian blue has formula Fe4[Fe(CN)6]3. The citric acid is taught as acidifying the PB nanoparticle. Other acids include HCl (page 7).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Szigeti et al. discloses the same Prussian blue core as claimed and a biocompatible coating comprising citrate which is the same as instantly claimed and suggests more than one biocompatible coating can be used and antibodies and/or polymers can be used, Szigeti et al. does not teach high molecular weight poly I:C or a broadly neutralizing antibody (bnAB). However, this deficiency is cured by Parks et al. and Zhou et al.
Parks et al. is directed to overcome steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization. VRC01-class antibodies are potent and broad HIV-1 neutralizing antibodies that offer protection from experimental animal (S)HIV (simian HIV) infection (page 3060). It is taught that the 426c Core immunogen elicits VRC01-like Abs that can recognize autologous and some heterologous soluble, stabilized Env trimers (page 3064, right column). It is taught that immunization with nanoparticle form of 426c Core with adjuvant poly(I:C) elicits robust autologous plasma antibody response (page 3061, right column).
Zhou et al. is directed to TLR3 activation efficacy by high or low molecular mass poly I:C. Innate immunity is important for the control of many viral infections including immunodeficiency virus (HIV) (page 1 first paragraph). Poly I:C has been used extensively as a TLR3 ligand to induce antiviral immunity (page 2, first paragraph). Taught is the study of the effectiveness of two commercially-available poly I:Cs: low molecular mass (0.2-1kb) and high molecular weight (1.5-8 kb) on TLR activation in various human cell types (page 2, first paragraph). It was shown that high molecular mass poly I:C induced stronger TLR3 activation than low molecular mass poly I:C which was evidenced by higher levels of IFN expression (page 5). Because of its ability to induce innate antiviral immunity, poly I:C has been suggested to be used as an adjuvant for vaccine therapy. Efforts in applying TLR3 ligand to enhance vaccine therapy has been made in mouse tumor implant model as well as in mouse viral infection model. It was demonstrated that TLR3 activation by poly I:C induced innate antiviral activity against HIV in macrophages and HSV-1 in neuronal cells (page 6).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Szigeti et al., Parks et al. and Zhou et al. and utilize a VRC01-class antibodies in combination with poly I:C and citrate as the biocompatible material. One skilled in the art would have been motivated to utilize citrate as it is a specifically taught biocompatible material. One skilled in the art would have been motivated to add a VRC01-class antibody and poly I:C when desiring to use the nanoparticles for a therapeutic purpose, such as immunization from experimental animal (S)HIV (simian HIV) infection. Since Szigeti et al. expressly teaches that the nanoparticles are used for drug delivery and suggest that antibodies can be used as one of the biocompatible coating material. It would have been obvious to utilize VRC01-class antibody as it is a specific antibody with therapeutic uses as taught by Parks et al. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C with the VRC01-class antibody as Parks et al. suggests that the two can be used together to elicits robust autologous plasma antibody response. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C as it has been shown to induced stronger TLR3 activation as taught by Zhou et al.
Regarding the claimed structure, Szigeti et al. expressly claims citrate as a biocompatible coating. This results in a positive charge on the surface of the Prussian Blue nanoparticles. As evidenced by Hafner et al., poly I:C is negatively charged (section 3.1). As evidenced by Scharf et al., VRC01-class bnAB are positively charged (page 2). Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Szigeti et al., Parks et al. and Zhou et al. and utilize a Prussian blue core with a negatively charged citrate coating followed by a positively charged VRC01-class bnAB coating followed by a negatively charged poly I:C coating. One skilled in the art would have been motivated to take advantage of the natural charges found in the components to allow for complexing to form stable nanoparticles for drug delivery.
Regarding claim 37, Zhou et al. teaches the high molecular mass poly I:C has 1.5 to 8 kb.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02. Furthermore Parks et al. and Zhou et al. teach that the poly I:C enhances immune cell activation.
Response to Arguments
Applicants’ arguments filed November 6 2024 have been fully considered but they are not persuasive.
Applicants argue (page 7) that (1) the office bears the burden of establishing a prima facie case of obviousness. It is argued that the office has not met this standard. The Office’s reliance on three references for treating the treatment of cancer is inapplicable to the currently pending claims. The Office action states that it is obvious to combine two compositions whish are taught for the same purpose in order to form a third composition to be used for that very same purpose. This purpose as set forth in the Office action is cancer. These references do not establish a prima face case of obviousness for the claimed nanoparticles that reverse HIV latency and enhance immune activation.
Regarding Applicants’ first argument, firstly, nothing in the claims recite a structural difference from the prior art. None of the claims refer to reversing HIV latency except new claim 38. However, this claim merely states the capabilities of the nanocomposite and does not structurally distinguish the instant claims from the prior art. While claim 1 as amended refers to poly I:C as a latency reversing agent, this is a property of the poly I:C. If the prior art suggests the use of poly I:C but for a different reason, it would still suggest the same poly I:C. It is well settled that "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007). As long as some suggestion to combine the elements is provided by the prior art as a whole, the law does not require that they be combined for the reason or advantage contemplated by the inventor. In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); In re Kroni, 539 F.2d 1300, 1304 (CCPA 1976). MPEP 2143.01 and 2144 (IV).
The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991)
In In re Lintner, the claimed invention was a laundry composition consisting essentially of a dispersant, cationic fabric softener, sugar, sequestering phosphate, and brightener in specified proportions. The claims were rejected over the combination of a primary reference which taught all the claim limitations except for the presence of sugar, and secondary references which taught the addition of sugar as a filler or weighting agent in compositions containing cationic fabric softeners. Appellant argued that in the claimed invention, the sugar is responsible for the compatibility of the cationic softener with the other detergent components. The court sustained the rejection, stating "The fact that appellant uses sugar for a different purpose does not alter the conclusion that its use in a prior art composition would be [sic, would have been] prima facie obvious from the purpose disclosed in the references." 173 USPQ at 562.
The fact that the prior art suggests the combination for treating cancer does not in and of itself make the combination non-obvious. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use orpurpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02 Note: MPEP 2145: Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991); see also In re Woodruff, 919 F.2d 1575, 1577-78 (Fed. Cir. 1990) (obviousness rejection affirmed where using claimed elements in the manner suggested by the prior art necessarily resulted in claim-recited effect). Therefore, Applicants arguments are not persuasive as they do not establish a structural difference between the claimed product and that suggested by the prior art.
Applicants argue (page 8-9 ) that (2) Appendix B is a demonstration that the enhanced immune activation achieved by the claimed nanoparticles was synergistic and was achieved only after incorporation the poly (I:C) on the PBNPs. Figure 2E (which corresponds to Fig. 5 in the present application) and Figure 2F show that coupling poly I:C to PBNPs increased their efficacy as latency reversing agents. Figures 3D and 3E confirmed that poly I:C-PBNPs achieved higher activation of both CD4 and C8 T cells. These are surprising and unexpected results (the examiner notes the arguments state that these are “expected” results but the examiner believes this is a typo and Applicants meant unexpected results).
Regarding Applicants’ second argument, where the combined action of two or more agents is greater than the sum of the action of one of the agents used alone, “synergy” according to the legally accepted definition exists. In re Kollman, 201 USPQ 193 (CCPA 1979). Claims drawn to (unexpectedly) synergistic combinations of known ingredients must be factually supported by data commensurate in scope with the claims. See, In re Kollman, 201 USPQ 193 (C.C.P.A. 1979). (The court affirming a 103 rejection of a claim containing the word “synergistic”, because the claims were not commensurate in scope with the showing of unexpected results, other than at 1:1 ratio for certain specific combinations). Here, while Figures 2E and 2F show a difference between Free polyIC and polyIC-PBNPs, the examiner cannot agree that this shows a synergistic effect. In order to show synergy, the data must show that the combination of polyIC and PBNps is greater than the additive effect (which is the sum of Free polyIC and free PBNps). That has not been established. While Figures 3D and 3E show the effect of PBNPs and polyIC alone and the combination. The examiner cannot agree that the results show a greater than additive effect. While the polyIC PBNPs combination is greater, looking at the numbers for the Y axis, it doesn’t appear the combination is any greater than the expected additive effect. The examiner notes that nowhere in the article submitted (appendix B) is synergy mentioned. The instant specification also does not mention synergy. Therefore, other than statement by the Attorney, no persuasive evidence has been presented hat the results are unexpected. Furthermore, even if the data were shown to be synergistic, the examiner cannot agree that the results are commensurate in scope. The data in the appendix B are specifically directed to PBNPs made by mixing Iron chloride hexahydrate and potassium hexacyanoferrate trihydrate and citric acid. It isn’t clear if this method results in a biocompatible coating comprising citrate as required by instant claim 1. Additionally, if it really is an unexpected effect between the Prussian blue material and the poly I:C then the data is only for a single Prussian blue material and no evidence has been presented that other materials falling within the scope of the claims would also possess an unexpected effect. 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) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). Note: MPEP 716.02(d). Furthermore, looking to the reference (Appendix B) it states for ideal polyIC size, zeta potential and ratio is important. None of those are recited in the instant claims (see synthesis of PolyIC-PBNPs section).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7 and 37-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9561183 in view of Szigeti et al., Pozuelo Rubio et al. and Xue et al. as evidenced by Dow et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a biofunctionalized nanocomposite, comprising:(a) a core comprising a nanoparticle formed of Prussian blue materials; (b) a shell obtained by partially or completely encapsulating the Prussian blue core with at least one biocompatible coating comprising citrate; and (c) at least one biomolecule attached to, or absorbed to, the biocompatible coating wherein the at least one biomolecule comprises a latency reversing agent (LRA), wherein the LRA comprises a high molecular weight poly I:C.
As claimed the nanocomposite further comprises a second biocompatible coating comprising polyethylenimine (PEI).
Patent ‘183 claims a composition comprising a core of doped Prussian blue and a shell of biocompatible coating. The claimed Prussian blue is an iron hexacyanoferrate and falls within the scope of instant claim 3. A method of imaging a tumor in a cell is claimed.
While Patent ‘183 claims a biocompatible coating, Patent ‘183 does not expressly claim a citrate coating, a PEI coating and poly(I:C). However these deficiencies are cured by Szigeti et al., Pozuelo Rubio et al. and Xue et al.
Szigeti et al. is directed to Prussian blue (PB) based nanoparticle as multimodal imaging contrast material. Claimed is a Prussian blue based nanoparticle comprising a Prussian blue based metal core doped with one or more metal isotopes and an organic biocompatible coating (reading on shell) (claim 1). The biocompatible coating comprises one or more biocompatible material such as polymers and citrate (claim 4). The nanoparticles can be used for therapy of different diseases or disorders such as mammary cancer (i.e. breast cancer) of all histological types (page 9). Example 1 shows Prussian with citric acid. The PB nanoparticles can also be used in imaging (example 11). The citric acid is taught as acidifying the PB nanoparticle. Other acids include HCl (page 7).
Pozuelo Rubio et al. is directed to novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine. The use of synthetic analogs of double-stranded RNA (dsRNA) that mimic viral dsRNA has been explored in recent years for specifically activating the immune system against tumors with the scope of inhibiting cancer cell growth and inducing cancer cell apoptosis. In particular, double-stranded polyinosinic-polycytidylic acid (named as poly(I:C) or pIC) has been characterized as a type of dsRNA with various effects of therapeutic interest against various cancers such as breast cancer (paragraph 0002). Unfortunately initial preclinical evidence shows naked poly(I:C) revealed its slow stability, poor homogeneity, unpredictable pharmacokinetics and limited antitumoral effects (paragraph 0003). The pitfalls that are limiting the clinical development of poly(I:C) molecules as a drug and its compliancy with regulatory requirements could be overcome by producing structurally complex anticancer complexes comprising poly(I:C) molecules together with drug delivery systems for cancer therapy that are often based on cationic polymers such as polyethyleneimine (PEI) (paragraph 0007). The poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight (paragraph 0296). Breast cancer is taught (paragraph 0224; 0234).
Xue et al. is directed to amine-modified preparation for carrying the Prussian blue magnetic nanoparticle of photosensitizer of polyethyleneimine (PEI). The particles have Prussian blue and a PEI coating which allows for a system with good biological compatibility for the treatment of breast cancer (abstract). The Prussian blue is acidified followed by coating with PEI (claim 1;5). The cationic polymer PEI is taught as being a bridge to other molecules such as a photosensitizer which can interact via electrostatic interaction (section 2, right before description).
Regarding claims 1, 4-5 and 7:
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘183, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and coat the Prussian blue nanoparticles of patent ‘183 with citrate and the cationic polymer polyethyleneimine (PEI). One skilled in the art would have been motivated to coat the particle with PEI to allow for further functionalization as taught by Xue et al. One skilled in the art would have been motivated to acidify the PB nanoparticles followed by coating with cationic PEI and expect a two layer coating on the nanoparticles would be formed. Furthermore, Xue et al. teaches coating after acidifying the Prussian blue nanoparticles. Therefore, there is a reasonable expectation of success in coating the nanoparticles of with the PEI and citrate as Patent ‘183 claims a biocompatible coating and citrate and PEI are both taught as biocompatible coatings which can be used to coat PB nanoparticles
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘183, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and utilize the combination of PEI and poly (I:C) with the nanoparticles of patent ‘183. Patent ‘183 teaches that the particles can be used for imaging a tumor cell. Szigeti et al. teaches that the particles can be used for imaging or therapy for cancers such as breast cancer. Xue et al. confirms that Prussian blue nanoparticles with a PEI coating can also be used for treating breast cancer. Pozuelo Rubio et al. teaches a complex of poly (I:C) and PEI can be utilized in the treatment of breast cancer. Therefore, one skilled in the art would have been motivated to combine Prussian blue with poly(I:C) as both are taught as being useful in the treatment of breast cancer. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Furthermore, the combination of Prussian blue with the poly(I:C) would allow for imaging of the cancer cells as well, an additional benefit. Pozuelo Rubio et al. teaches the poly(I:C) complexes with the PEI. Therefore, a coating of the PEI complexed with the poly(I:C) would result in the biomolecule being attached to, or absorbed to the biocompatible coating.
Regarding the claimed high molecular weight poly I:C and claim 37, Pozuelo Rubio et al. teaches the poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight. Therefore, it would have been obvious to utilize the commercial source of poly(I:C) taught by Pozuelo Rubio et al. As evidenced by Dow et al., poly I:C obtained from invivogen with a high molecular weight has an average size of 1.5-8 kb (paragraph 0074).
Regarding claims 2-3, Szigeti et al. exemplifies Fe4[Fe(CN)6]3 which is an iron hexacyanoferrate. The Prussian blue formula taught by Szigeti et al. overlaps in scope with instantly claimed general formula I.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02
Claims 17 and 37-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9561183 in view of Szigeti et al., Parks et al. (Cell Reports, 2019) and Zhou et al. (Innate Immun. 2014) as evidenced by Scharf et al. (eLife, 2016) and Hafner et al. (Biomaterials, 2011). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims the nanocomposite further comprises a second biomolecule attached to, or absorbed to, the biocompatible coating, wherein the second biomolecule comprises at least one broadly neutralizing antibody (bnAB) against human immunodeficiency virus (HIV), and wherein the at least one bnAB comprises 3BNC117, VRCO1, VRC02, or 10-1074.
The instant application claims a biofunctionalized nanocomposite, comprising:(a) a core comprising a nanoparticle formed of Prussian blue materials;(b) a shell obtained by partially or completely encapsulating the Prussian blue core with at least one biocompatible coating comprising citrate;(c) high molecular weight (HIIW) polyinosine-polycytidylic acid (poly I:C) attached to, or absorbed to, the biocompatible coating, and(d) at least one broadly neutralizing antibody (bnAB) against human
The claims of Patent ‘183 are set forth above. As claimed the biocompatible coating is in contact with the core by physical or chemical interactions which include electrostatic interactions. A peptide is claimed.
While Patent ‘183 claims the same Prussian blue core as claimed and a biocompatible coating Patent ‘183 does not teach citrate coating, high molecular weight poly I:C or a broadly neutralizing antibody (bnAB). However, these deficiencies are cured by Szigeti et al., Parks et al. and Zhou et al.
The teachings of Szigeti et al. are set forth above.
Parks et al. is directed to overcome steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization. VRC01-class antibodies are potent and broad HIV-1 neutralizing antibodies that offer protection from experimental animal (S)HIV (simian HIV) infection (page 3060). It is taught that the 426c Core immunogen elicits VRC01-like Abs that can recognize autologous and some heterologous soluble, stabilized Env trimers (page 3064, right column). It is taught that immunization with nanoparticle form of 426c Core with adjuvant poly(I:C) elicits robust autologous plasma antibody response (page 3061, right column).
Zhou et al. is directed to TLR3 activation efficacy by high or low molecular mass poly I:C. Innate immunity is important for the control of many viral infections including immunodeficiency virus (HIV) (page 1 first paragraph). Poly I:C has been used extensively as a TLR3 ligand to induce antiviral immunity (page 2, first paragraph). Taught is the study of the effectiveness of two commercially-available poly I:Cs: low molecular mass (0.2-1kb) and high molecular weight (1.5-8 kb) on TLR activation in various human cell types (page 2, first paragraph). It was shown that high molecular mass poly I:C induced stronger TLR3 activation than low molecular mass poly I:C which was evidenced by higher levels of IFN expression (page 5). Because of its ability to induce innate antiviral immunity, poly I:C has been suggested to be used as an adjuvant for vaccine therapy. Efforts in applying TLR3 ligand to enhance vaccine therapy has been made in mouse tumor implant model as well as in mouse viral infection model. It was demonstrated that TLR3 activation by poly I:C induced innate antiviral activity against HIV in macrophages and HSV-1 in neuronal cells (page 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘183, Szigeti et al., Parks et al. and Zhou et al. and utilize a VRC01-class antibodies in combination with poly I:C and citrate as the biocompatible material. One skilled in the art would have been motivated to utilize citrate as it is a specifically taught biocompatible material. One skilled in the art would have been motivated to add a VRC01-class antibody and poly I:C when desiring to use the nanoparticles for a therapeutic purpose, such as immunization from experimental animal (S)HIV (simian HIV) infection. Since Szigeti et al. expressly teaches that the nanoparticles are used for drug delivery and suggest that antibodies can be used as one of the biocompatible coating material. It would have been obvious to utilize VRC01-class antibody as it is a specific antibody with therapeutic uses as taught by Parks et al. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C with the VRC01-class antibody as Parks et al. suggests that the two can be used together to elicits robust autologous plasma antibody response. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C as it has been shown to induced stronger TLR3 activation as taught by Zhou et al.
Regarding the claimed structure, Szigeti et al. expressly claims citrate as a biocompatible coating. This results in a positive charge on the surface of the Prussian Blue nanoparticles. As evidenced by Hafner et al., poly I:C is negatively charged (section 3.1). As evidenced by Scharf et al., VRC01-class bnAB are positively charged (page 2). Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Szigeti et al., Parks et al. and Zhou et al. and utilize a Prussian blue core with a negatively charged citrate coating followed by a positively charged VRC01-class bnAB coating followed by a negatively charged poly I:C coating. One skilled in the art would have been motivated to take advantage of the natural charges found in the components to allow for complexing to form stable nanoparticles for drug delivery. Since patent ‘183 claims electrostatic interactions between the biocompatible coating at the core there is a reasonable expectation of success.
Regarding claim 37, Zhou et al. teaches the high molecular mass poly I:C has 1.5 to 8 kb.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02. Furthermore Parks et al. and Zhou et al. teach that the poly I:C enhances immune cell activation.
Claims 1-5, 7 and 37-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9987378 in view of Szigeti et al., Pozuelo Rubio et al. and Xue et al. as evidenced by Dow et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘378 claims a composition comprising a core of doped Prussian blue and a shell of biocompatible coating. The Prussian blue is of formula I which overlaps in scope with instant claim 3 and includes iron hexacyanoferrate compounds. An imaging agent comprising the composition is claimed.
While Patent ‘378 claims a biocompatible coating, Patent ‘378 does not expressly claim a citrate coating, a PEI coating and poly(I:C). However these deficiencies are cured by Szigeti et al., Pozuelo Rubio et al. and Xue et al.
The teachings of Szigeti et al., Pozuelo Rubio et al. and Xue et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘378, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and coat the Prussian blue nanoparticles of patent ‘378 with citrate and the cationic polymer polyethyleneimine (PEI). One skilled in the art would have been motivated to coat the particle with PEI to allow for further functionalization as taught by Xue et al. One skilled in the art would have been motivated to acidify the PB nanoparticles followed by coating with cationic PEI and expect a two layer coating on the nanoparticles would be formed. Furthermore, Xue et al. teaches coating after acidifying the Prussian blue nanoparticles. Therefore, there is a reasonable expectation of success in coating the nanoparticles of with the PEI and citrate as Patent ‘378 claims a biocompatible coating and citrate and PEI are both taught as biocompatible coatings which can be used to coat PB nanoparticles
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘378, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and utilize the combination of PEI and poly (I:C) with the nanoparticles of patent ‘378. Patent ‘378 teaches that the particles can be used for imaging. Szigeti et al. teaches that the particles can be used for imaging or therapy for cancers such as breast cancer. Xue et al. confirms that Prussian blue nanoparticles with a PEI coating can also be used for treating breast cancer. Pozuelo Rubio et al. teaches a complex of poly (I:C) and PEI can be utilized in the treatment of breast cancer. Therefore, one skilled in the art would have been motivated to combine Prussian blue with poly(I:C) as both are taught as being useful in the treatment of breast cancer. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Furthermore, the combination of Prussian blue with the poly(I:C) would allow for imaging of the cancer cells as well, an additional benefit. Pozuelo Rubio et al. teaches the poly(I:C) complexes with the PEI. Therefore, a coating of the PEI complexed with the poly(I:C) would result in the biomolecule being attached to, or absorbed to the biocompatible coating.
Regarding the claimed high molecular weight poly I:C and claim 37, Pozuelo Rubio et al. teaches the poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight. Therefore, it would have been obvious to utilize the commercial source of poly(I:C) taught by Pozuelo Rubio et al. As evidenced by Dow et al., poly I:C obtained from invivogen with a high molecular weight has an average size of 1.5-8 kb (paragraph 0074).
Regarding claims 2-3, Szigeti et al. exemplifies Fe4[Fe(CN)6]3 which is an iron hexacyanoferrate. The Prussian blue formula taught by Szigeti et al. overlaps in scope with instantly claimed general formula I.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02
Claims 17 and 37-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9987378 in view of Szigeti et al., Parks et al. and Zhou et al. as evidenced by Scharf et al. and Hafner et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application are set forth above.
The claims of Patent ‘378 are set forth above. As claimed the biocompatible coating is in contact with the core by physical or chemical interactions which include electrostatic interactions. A peptide is claimed.
While Patent ‘378 claims the same Prussian blue core as claimed and a biocompatible coating Patent ‘378 does not teach citrate coating, high molecular weight poly I:C or a broadly neutralizing antibody (bnAB). However, these deficiencies are cured by Szigeti et al., Parks et al. and Zhou et al.
The teachings of Szigeti et al., Parks et al. and Zhou et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘378, Szigeti et al., Parks et al. and Zhou et al. and utilize a VRC01-class antibodies in combination with poly I:C and citrate as the biocompatible material. One skilled in the art would have been motivated to utilize citrate as it is a specifically taught biocompatible material. One skilled in the art would have been motivated to add a VRC01-class antibody and poly I:C when desiring to use the nanoparticles for a therapeutic purpose, such as immunization from experimental animal (S)HIV (simian HIV) infection. Since Szigeti et al. expressly teaches that the nanoparticles are used for drug delivery and suggest that antibodies can be used as one of the biocompatible coating material. It would have been obvious to utilize VRC01-class antibody as it is a specific antibody with therapeutic uses as taught by Parks et al. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C with the VRC01-class antibody as Parks et al. suggests that the two can be used together to elicits robust autologous plasma antibody response. One skilled in the art would have been motivated to utilize a high molecular weight poly I:C as it has been shown to induced stronger TLR3 activation as taught by Zhou et al.
Regarding the claimed structure, Szigeti et al. expressly claims citrate as a biocompatible coating. This results in a positive charge on the surface of the Prussian Blue nanoparticles. As evidenced by Hafner et al., poly I:C is negatively charged (section 3.1). As evidenced by Scharf et al., VRC01-class bnAB are positively charged (page 2). Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Szigeti et al., Parks et al. and Zhou et al. and utilize a Prussian blue core with a negatively charged citrate coating followed by a positively charged VRC01-class bnAB coating followed by a negatively charged poly I:C coating. One skilled in the art would have been motivated to take advantage of the natural charges found in the components to allow for complexing to form stable nanoparticles for drug delivery. Since patent ‘378 claims electrostatic interactions between the biocompatible coating at the core there is a reasonable expectation of success.
Regarding claim 37, Zhou et al. teaches the high molecular mass poly I:C has 1.5 to 8 kb.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02. Furthermore Parks et al. and Zhou et al. teach that the poly I:C enhances immune cell activation.
Claims 1-5, 7 and 37-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11672861 in view of Szigeti et al., Pozuelo Rubio et al. and Xue et al. as evidenced by Dow et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘861 claims a biofunctionalized nanocomposite, comprising: (a) a core comprising Prussian blue materials; (b) a positively charged biocompatible coating comprising polyethylenimine (PEI) having an average molecular weight (MW) of about 2000 Daltons; and at least one CpG oligodeoxynucleotide attached to the outer surface of the positively charged biocompatible coating. Iron hexacyanoferrate is claimed. The same formula for Prussian blue as instantly claimed (claim 3) is claimed.
While Patent ‘861 claims a PEI coating, Patent ‘861 does not claim a citrate coating or poly(I:C). However, this deficiency is cured by Szigeti et al., Pozuelo Rubio et al. and Xue et al.
The teachings of Szigeti et al., Pozuelo Rubio et al. and Xue et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘861, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and coat the Prussian blue nanoparticles of patent ‘861 with citrate and the cationic polymer polyethyleneimine (PEI). One skilled in the art would have been motivated to acidify the PB nanoparticles followed by coating with cationic PEI and expect a two layer coating on the nanoparticles would be formed. Furthermore, Xue et al. teaches coating after acidifying the Prussian blue nanoparticles. Therefore, there is a reasonable expectation of success in coating the nanoparticles of with the PEI and citrate as Patent ‘861 claims a biocompatible coating comprising PEI and citrate and PEI are both taught as biocompatible coatings which can be used to coat PB nanoparticles
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘861, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and utilize the combination of PEI and poly (I:C) with the nanoparticles of patent ‘861. Szigeti et al. teaches that the particles can be used for imaging or therapy for cancers such as breast cancer. Xue et al. confirms that Prussian blue nanoparticles with a PEI coating can also be used for treating breast cancer. Pozuelo Rubio et al. teaches a complex of poly (I:C) and PEI can be utilized in the treatment of breast cancer. Therefore, one skilled in the art would have been motivated to combine Prussian blue with poly(I:C) as both are taught as being useful in the treatment of breast cancer. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Furthermore, the combination of Prussian blue with the poly(I:C) would allow for imaging of the cancer cells as well, an additional benefit. Pozuelo Rubio et al. teaches the poly(I:C) complexes with the PEI. Therefore, a coating of the PEI complexed with the poly(I:C) would result in the biomolecule being attached to, or absorbed to the biocompatible coating.
Regarding the claimed high molecular weight poly I:C and claim 37, Pozuelo Rubio et al. teaches the poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight. Therefore, it would have been obvious to utilize the commercial source of poly(I:C) taught by Pozuelo Rubio et al. As evidenced by Dow et al., poly I:C obtained from invivogen with a high molecular weight has an average size of 1.5-8 kb (paragraph 0074).
Regarding claims 2-3, Szigeti et al. exemplifies Fe4[Fe(CN)6]3 which is an iron hexacyanoferrate. The Prussian blue formula taught by Szigeti et al. overlaps in scope with instantly claimed general formula I.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02.
Claims 1-5, 7 and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 18814236 (USPGPUB No. 20240415773) in view of Szigeti et al., Pozuelo Rubio et al. and Xue et al. as evidenced by Dow et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
Copending ‘236 claims a method of treating a subject, the method comprising: (i) administering to a subject having cancer a biofunctionalized nanocomposite, wherein the biofunctionalized nanocomposite comprises a core comprising a nanoparticle formed of Prussian blue materials; a shell obtained by partially or completely encapsulating the Prussian blue core with a biocompatible coating; and at least one anti-CD137 antibody attached to, or absorbed to, the biocompatible coating; and (ii) subjecting the subject to photothermal therapy. The Prussian blue materials are iron hexacyanoferrate compounds. The Prussian blue materials are of formula II which overlaps in scope with instant claim 3. A shell of PEI is claimed.
While copending ‘236 claims a PEI coating, copending ‘236 does not claim a citrate coating or poly(I:C). However, this deficiency is cured by Szigeti et al., Pozuelo Rubio et al. and Xue et al.
The teachings of Szigeti et al., Pozuelo Rubio et al. and Xue et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘236, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and coat the Prussian blue nanoparticles of copending ‘236 with citrate and the cationic polymer polyethyleneimine (PEI). One skilled in the art would have been motivated to acidify the PB nanoparticles followed by coating with cationic PEI and expect a two layer coating on the nanoparticles would be formed. Furthermore, Xue et al. teaches coating after acidifying the Prussian blue nanoparticles. Therefore, there is a reasonable expectation of success in coating the nanoparticles of with the PEI and citrate as copending ‘236 claims a biocompatible coating comprising PEI and citrate and PEI are both taught as biocompatible coatings which can be used to coat PB nanoparticles
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘236, Szigeti et al., Pozuelo Rubio et al. and Xue et al. and utilize the combination of PEI and poly (I:C) with the nanoparticles of copending ‘236. Szigeti et al. teaches that the particles can be used for imaging or therapy for cancers such as breast cancer. Xue et al. confirms that Prussian blue nanoparticles with a PEI coating can also be used for treating breast cancer. Pozuelo Rubio et al. teaches a complex of poly (I:C) and PEI can be utilized in the treatment of breast cancer. Therefore, one skilled in the art would have been motivated to combine Prussian blue with poly(I:C) as both are taught as being useful in the treatment of breast cancer. As a general principle 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, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Furthermore, the combination of Prussian blue with the poly(I:C) would allow for imaging of the cancer cells as well, an additional benefit. Pozuelo Rubio et al. teaches the poly(I:C) complexes with the PEI. Therefore, a coating of the PEI complexed with the poly(I:C) would result in the biomolecule being attached to, or absorbed to the biocompatible coating.
Regarding the claimed high molecular weight poly I:C and claim 37, Pozuelo Rubio et al. teaches the poly(I:C) is commercially available from invivogen in high molecular weight and low molecular weight. Therefore, it would have been obvious to utilize the commercial source of poly(I:C) taught by Pozuelo Rubio et al. As evidenced by Dow et al., poly I:C obtained from invivogen with a high molecular weight has an average size of 1.5-8 kb (paragraph 0074).
Regarding claims 2-3, Szigeti et al. exemplifies Fe4[Fe(CN)6]3 which is an iron hexacyanoferrate. The Prussian blue formula taught by Szigeti et al. overlaps in scope with instantly claimed general formula I.
Regarding claim 38, this claim merely states the capabilities of the nanocomposite. Since as set forth above, the structure of the nanocomposite of the claims is the same as what is suggested by the prior art, the nanoparticles of the prior art would be capable of performing the claimed function. "the patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801,809 (Fed. Cir. 2002). Note: MPEP 2111.02
Response to Arguments
Applicants’ arguments filed November 6 2025 have been fully considered but they are not persuasive.
Applicants argue that the amendments to the claims overcome the rejections. Applicant request that the office hold these double patenting rejection in abeyance.
Regarding applicants arguments, firstly, the arguments are not persuasive for the same reasons set forth above in the response to the 103 rejections. Secondly, Applicant(s) is/are reminded that a request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see MPEP 714.02 and CFR 1.111(b)).
Conclusion
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.
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636