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 .
Information Disclosure Statement
The submitted information disclosure statement (IDS) were filed on 05/20/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Application
Applicants' arguments/remarks filed 04/30/2026 are acknowledged. Claim 1 is currently amended. Claims 2-3, 6, 9, 10, 12, 14-15, 19-24 were previously canceled. Claims 4-5, 7-8, 11, 13, 16-18 are newly canceled. Claims 25-42 are newly added. Claims 1 and 25-42 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicants' amendment, and with respect to applicant’s arguments/remarks filed 04/30/2026,
the rejection of claims 2-24 under 35 U.S.C. 103 has been withdrawn in view of the cancelation of the claims.
the rejection of claims 1, 4-5, 7-8, 11, 13, 16-18 under 35 U.S.C. 103 has been withdrawn in view of the amendments of claim 1.
Modified Rejections
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 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 non-obviousness.
Claims 1, 27-42 are rejected under 35 U.S.C. 103 as being obvious over An et al., (CN 109847073 A) and Huang et al., (Huang et al., pH-Responsive nanodrug encapsulated by tannic acid complex for controlled drug delivery. RSC Adv., 2017, 7, 2829) in view of Zitvogel et al. (US 20130156790 A1) and Tang et al. (Tang et al., Combination therapy with proteasome inhibitors and TLR agonists enhances tumor cell death and IL-1β production. Cell Death and Disease (2018) 9:162) and Kashiwazaki et al. (Kashiwazaki et al., Immunomodulatory Effects of Proteasome Inhibitors in Multiple Myeloma Blood (2018) 132 (Supplement 1) : 1946.) and Puente et al. (Puente et al., Nanoparticle delivery systems, general approaches, and their
implementation in multiple myeloma. Eur J Haematol. 2017;98:529–541).
Claims 1 and 27-35 are composition claims, where “for cancer treatment” and “within a tumor microenvironment at a level sufficient to induce immunogenic cell death and while reducing cytotoxicity to immune cells present in the tumor microenvironment; promotes induction of damage-associated molecular patterns (DAMPs) from tumor cells; further function as a reservoir for tumor-associated antigens and DAMPs released from dying tumor cells; retards diffusion of carfilzomib from the nanoparticles and stabilizes the nanoparticles in serum; composition is administered locally at the site of a tumor by intratumoral administration; composition is administered systemically; sustained intratumoral release of carfilzomib sufficient to induce immunogenic cell death; layer reduces premature drug release in circulation; and is administered intratumorally,” are for intended use limitations and “is formed by interfacial assembly” are for method of preparation so they have no patentable weight.
An et al. teach nanoparticles of tannic acid (TA) complexed with Fe3+ ions and with bovine serum albumin (BSA) adsorption on the TA coating. (Abs). An et al. teach albumin (alb) coated tannic acid-Fe (pTA) nanoparticles (NPs).
Huang et al. teach the metal ion/polyphenol complexation encapsulating paclitaxel nanodrug (PTX-C), (Abs), for controllable drug release, (pg. 1, right col., 2nd par.).
An et al. and Huang et al. teach TA nanoparticles and Huang teach TA encapsulating paclitaxel, and these nanoparticles encapsulating drugs are engineered for targeted and controlled drug release.
An et al. and Huang et al. teach TA nanoparticles and Huang teach paclitaxel encapsulation, but do not recite teach the composition comprising one or more diluents, excipients or carriers and Carfilzomib that induces immunogenic cell death (ICD).
Zitvogel et al. teach several anti-cancer therapeutics, amongst which feature chemotherapy anthracyclines such as doxorubicin (DX), idarubicin and mitoxantrone (MTX), oxali-platinum (oxaliplatin or OXP), taxanes (paclitaxel or docetaxel), and cyclophosphamide/alkylating. (0008). They are also compound to induce immunogenic cancer cell death in a subject, (Title), the drugs to induce immunogenic cell death (0606), a therapeutic for treatment of cancer, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject (Abs). Appropriate excipient, diluent or carrier may be selected. (0518).
An et al. and Huang et al. do not teach drugs that induces immunogenic cell death (ICD).
Tang et al. teach. Carfilzomib, one of proteozome inhibitors, (Fig. 1, pg. 2), with promising characteristic of proteasome inhibitors is their ability to induce immunogenic cell death (ICD), which has been shown to elicit anti-tumor responses. (pg. 2, left col., 2nd par.).
Kashiwazaki et al. teach that proteasome inhibitors, comprising carfilzomib, could not only directly kill Multiple Myeloma (MM) cells but also induce anti-myeloma immune response via Immunogenic Cell Death (ICD). (Abs).
An et al. teach TA-NPs has low toxicity; Huang et al. teach Design of stimuli-responsive drugs is a promising approach to reduce systemic toxicity and enhance therapeutic outcome of the drugs. (pg. 2832, right col., 2nd par.), and the in vivo results indicate that PTX-C possesses an excellent anti-tumor ability at lower systematic toxicity, (pg. 2834, right col., 1st par.), which means lower doses are needed and also contributes additionally to lower systemic toxicity; Puente et al. teach NPs drug delivery system (NPDDS) in general reduce systemic toxicity (Table 1, pg. 530; Table 2, pg. 535), Carfilzomib in micelles improved cytotoxicity and Carfilzomib in magnetic NPs reduced body weight loss; Tumor growth inhibition and higher accumulation at the tumor; (Table 2, pg. 535),which means NPDDS reduce toxicity for all cells, including immune cells relative to free carfilzomib.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare nanoparticle compositions, of tannic acid (TA) complexed with Fe3+ ions coated with albumin adsorption on the TA, taught by An et al., and the anticancer drug encapsulated in the metal ion/polyphenol complexation, for controlled release drug, taught by Huang et al., composition comprising drug(s) to induce immunogenic cell death with appropriate excipient, diluent or carrier, taught by Zitvogel et al., and instead of paclitaxel, carfilzomib, a proteasome inhibitor, which induce ICD, taught by Tang et al. and Kashiwazaki et al., could be encapsulated in tannic acid (TA) complexed with Fe3+ ions coated with albumin adsorption on the TA since the ideas have been studied and proven they would be feasible to do so.
With regard to claims 30-31,
Huang et al. teach PTX-NPs was administrated intravenously. (Fig. 4, pg. 2834).
Puente et al. teach NPs were injected intratumorally, (pg. 534, right col., last par.); and Carfilzomib NPs dosed IV; nanoparticles (NPs) can be dosed intravenous (IV), subcutaneous (SC), intratumoral (IT), intraperitoneal (IP), (Table 2, pg. 535).
Claims 36-40 and 42 are method claims, which have no specific details on how they are administered in a tumor microenvironment, on how they are reducing cytotoxicity to tumor-infiltrating immune cells, on how they are effective in the tumor microenvironment, on how they induce activation of antigen-presenting cells within or proximate to microenvironment how the administration results in development of a local or systemic antitumor immune response and how immune cells within the tumor microenvironment exhibit higher viability than when treated with an equivalent dose of unencapsulated carfilzomib in claim limitations so they don’t have patentable weight.
Claims 36-38 and 42,
An et al. teach nanoparticles of tannic acid (TA) complexed with Fe3+ ions and with bovine serum albumin (BSA) adsorption on the TA coating. (Abs). An et al. teach albumin (alb) coated tannic acid-Fe (pTA) nanoparticles (NPs).
Huang et al. teach the metal ion/polyphenol complexation encapsulating paclitaxel nanodrug (PTX-C), (Abs), for controllable drug release, (pg. 1, right col., 2nd par.). The method of treatment comprising: administration of a dosage of 10 mg/kg (with respect to PTX) intravenously in subjects, and the tumor volumes were measured at the indicated time points (n ¼ 6–8). (Fig. 4, pg. 2834). The method of treatment in a subject comprising administering drug encapsulated in TA, with an effective amount to destroy cancer cells and to induce tumor shrinking.
An et al. and Huang et al. teach TA nanoparticles and Huang teach TA encapsulating paclitaxel, and these nanoparticles encapsulating drugs are engineered for targeted and controlled drug release.
An et al. and Huang et al. teach TA nanoparticles and Huang teach paclitaxel encapsulation, but do not recite teach the composition comprising one or more diluents, excipients or carriers and Carfilzomib that induces immunogenic cell death (ICD).
Zitvogel et al. teach several anti-cancer therapeutics, amongst which feature chemotherapy anthracyclines such as doxorubicin (DX), idarubicin and mitoxantrone (MTX), oxali-platinum (oxaliplatin or OXP), taxanes (paclitaxel or docetaxel), and cyclophosphamide/alkylating. (0008). They are also compound to induce immunogenic cancer cell death in a subject, (Title), the drugs to induce immunogenic cell death (0606), a therapeutic for treatment of cancer, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject (Abs). Appropriate excipient, diluent or carrier may be selected. (0518).
An et al. and Huang et al. do not teach drugs that induces immunogenic cell death (ICD).
Tang et al. teach Carfilzomib, one of proteozome inhibitors, (Fig. 1, pg. 2), with promising characteristic of proteasome inhibitors is their ability to induce immunogenic cell death (ICD), which has been shown to elicit anti-tumor responses. (pg. 2, left col., 2nd par.). Proteasome inhibitors have emerged as an effective therapy for the treatment of haematological malignancies.
Kashiwazaki et al. teach that proteasome inhibitors, comprising carfilzomib, could not only directly kill Multiple Myeloma (MM) cells but also induce anti-myeloma immune response via Immunogenic Cell Death (ICD). (Abs).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare nanoparticle compositions, of tannic acid (TA) complexed with Fe3+ ions coated with albumin adsorption on the TA, taught by An et al., administering an effective amount of drug/TA the anticancer drug encapsulated in the metal ion/polyphenol complexation, for sustained release drug taught by Huang et al.; composition comprising drug(s) to induce immunogenic cell death and instead of paclitaxel, carfilzomib, a proteasome inhibitor, which induce ICD, taught by Tang et al. and Kashiwazaki et al., could be encapsulated in tannic acid (TA) complexed with Fe3+ ions coated with albumin adsorption on the TA since the ideas have been studied and proven they would be feasible to do so.
With regard to claims 39-40,
Huang et al. teach PTX-NPs was administrated intravenously. (Fig. 4, pg. 2834).
Puente et al. teach NPs were injected intratumorally, (pg. 534, right col., last par.); and Carfilzomib NPs dosed IV; nanoparticles (NPs) can be dosed intravenous (IV), subcutaneous (SC), intratumoral (IT), intraperitoneal (IP), (Table 2, pg. 535).
With regard to claim 41,
Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the (product-by-process) claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). MPEP 2173 .05(p ).
An et al. teach the preparation method comprises the following steps:
(1) dissolving the bovine serum albumin in A secondary water,
(2) the soluble trivalent ferric salt and the soluble bivalent iron salt are added in the secondary water B, dissolving to obtain the iron source solution;
(3) adding bovine serum albumin solution in inert atmosphere. to prepare BSA-Fe precursor. (pg. 2, 2nd par.).
Huang et al. teach this process to encapsulate a drug, dissolved PTX molecules into particles and the prepared PTX-NPs were coated immediately with the natural polyphenols and FeIII. (pg. 2830, right col, 1st par.).
When the drug is carfilzomib, PTX is replaced by carfilzomib
With regard to claims 39-40,
Huang et al. teach PTX-NPs was administrated intravenously. (Fig. 4, pg. 2834).
Puente et al. teach NPs were injected intratumorally, (pg. 534, right col., last par.); and Carfilzomib dosed IV; NPs, nanoparticles; IV, intravenous; SC, subcutaneous; IT., intratumoral; IP, intraperitoneal; (Table 2, pg. 535).
With regard to claim 42
An et al. teach TA-NPs has low toxicity; Huang et al. teach Design of stimuli-responsive drugs is a promising approach to reduce systemic toxicity and enhance therapeutic outcome of
the drugs. (pg. 2832, right col., 2nd par.). The in vivo results indicate that PTX-C
possesses an excellent anti-tumor ability at lower systematic toxicity, (pg. 2834, right col., 1st par.); Puente teach NPs drug delivery system (NPDDS) in general reduce systemic toxicity (Table 1, pg. 530; Table 2, pg. 535), Carfilzomib in micelles improved cytotoxicity and Carfilzomib in magnetic NPs reduced body weight loss; Tumor growth inhibition and higher
accumulation at the tumor; (Table 2, pg. 535),which means NPDDS reduce toxicity for all cells, including immune cells relative to free carfilzomib, which mean tumor microenvironment has higher biability than when treated with unencapsulated carfilzomib.
Response to Arguments
Claim Rejections
II: Claims 1, 5, 7-8, and 11
Applicant argues that:
The Cited References Fail to Teach or Suggest the Claimed Mechanism of ICD Induction
B. An et al. Do Not Teach ICD, Immune Sparing, or Sustained Intratumoral Delivery
C. Huang et al. Teach Encapsulation, Not Immunogenic Cell Death
D. Zitvogel et al. Do Not Teach the Claimed Nanoparticle-Based ICD Mechanism
E. No Reasonable Expectation of Success Exists
Applicant's arguments have been fully considered but they are not persuasive since the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. Please see the modified rejection above. And when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012).
And, Claims 5, 7-8, and 11 are canceled. There are no rejections of claims 5, 7-8, and 11.
III: Claims 1 and 4
Applicant argues that The Examiner relies on JP 2018-510636 A to supply proteasome inhibitors such as carfilzomib. Applicant submits that JP '636 does not remedy the deficiencies noted above.
Applicant's arguments have been fully considered but they are moot since claim 4 is canceled. Prior art JP 2018-510636 A is removed. There is no rejection of claim 4.
IV: Claims 7 and 13-18
Applicant argues that The Office cites In re Thorpe for the proposition that product-by-process claims are unpatentable if the product is the same as or obvious from the prior art. Applicant does not dispute this legal principle but submits that it is inapplicable here.
Applicant's arguments have been fully considered but they are moot since claims 7 and 13-18 are canceled. There are no rejections of claims 7 and 13-18.
V. Unexpected Results and Secondary Considerations
Applicant argues that:
• reduced cytotoxicity to immune cells relative to free carfilzomib;
• enhanced tumor retention;
• activation of antigen-presenting cells; and
• development of local and systemic anti-tumor immunity following local administration.
These results are not predictable from the cited art and further support non-obviousness under
Graham v. John Deere.
Applicant's arguments have been fully considered but they are not persuasive since An et al. teach TA-NPs has low toxicity; Huang et al. teach Design of stimuli-responsive drugs is a promising approach to reduce systemic toxicity and enhance therapeutic outcome of the drugs. (pg. 2832, right col., 2nd par.), and the in vivo results indicate that PTX-C possesses an excellent anti-tumor ability at lower systematic toxicity, (pg. 2834, right col., 1st par.), which means lower doses are needed and also contributes additionally to lower systemic toxicity; Puente et al. teach NPs drug delivery system (NPDDS) in general reduce systemic toxicity (Table 1, pg. 530; Table 2, pg. 535), Carfilzomib in micelles improved cytotoxicity and Carfilzomib in magnetic NPs reduced body weight loss; Tumor growth inhibition and higher accumulation at the tumor; (Table 2, pg. 535),which means NPDDS reduce toxicity for all cells, including immune cells relative to free carfilzomib. Zitvogel et al. teach compounds induce immunogenic cell death in a subject. (Title). The cell death modality triggered by chemotherapy or radiotherapy allows recognition of dying tumor cells by antigen presenting cells, thus eliciting a tumor specific cognate immune response which is critical for tumor elimination. (0009). The cell death immunogenicity depends on the lethal stimulus, on the presence of specific signals produced by or exposed on tumor cells, as well as on the ability of the subject having the tumor, and in particular of the subject's immune system, to recognize said signals. (0013). Kashiwazaki et al. teach that proteasome inhibitors, comprising carfilzomib, could not only directly kill Multiple Myeloma (MM) cells but also induce anti-myeloma immune response via Immunogenic Cell Death (ICD). (Abs). It would be obvious that carfilzomib, which induces ICD and would active antigen presenting cells, allows recognition of dying tumor cells by antigen presenting cells, thus eliciting a tumor specific cognate immune response which is critical for tumor elimination. (0009). Applicant could provide detailed descriptions and specific results in claims limitations, to increase chance for allowance.
Conclusion
Applicants' 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 extension fee 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 date of this final action.
Correspondence
No claim is allowed
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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