DETAILED ACTION
Applicants’ arguments, filed 5 December 2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
Claim 1 recites “polyoxide” as of the last word on the 6th to last line of the claim. “Polyoxide” is not a standard term in organic polymer chemistry. While the term “polyoxide” may be a standard term in inorganic chemistry, this is not relevant here as the term “hydrophilic polymer” refers to an organic polymer.
Nevertheless, as best understood by the examiner, a polyoxide is understood to be the same as a polyether, as a polyether comprises repeating oxygen atoms spaced by alkylene groups between the oxygen atoms. For the purposes of examination under prior art, only polyethers that can reasonably be considered hydrophilic are understood to be part of the scope of claim 1.
Claim 1 recites that the hydrophilic polymer is covalently bound to a carboxyl group of the bilirubin. The chemical structure of bilirubin has been reproduced below from Bonnett et al. (Nature, Vol. 262, July 1976, pages 326-328), as of the left column on page 327, with various features pointed out by the examiner.
PNG
media_image1.png
325
518
media_image1.png
Greyscale
As best understood by the examiner, the term “carboxyl” refers to a carboxylic acid. The examiner takes the position that, upon covalently bonding the carboxyl group of the bilirubin to the hydrophilic polymer, the carboxyl group would cease to be a carboxylic acid and would become a different functional group, most likely an ester or amide. An ester would form upon bonding of the carboxyl of bilirubin to a hydroxyl (alcohol) of the hydrophilic polymer. An amide would form upon bonding of the carboxyl of bilirubin to an amine of the hydrophilic polymer.
As such, the limitation “the hydrophilic polymer is covalently bound to a carboxyl group of the bilirubin” is interpreted as requiring that a chemical bond is formed between the group that was the carboxyl group of bilirubin prior to bonding and the hydrophilic polymer. The carboxyl group need not remain a carboxyl group following bonding, and is most likely an ester or amide group, but is not necessarily limited to an ester or amide.
Withdrawn Rejection and Objections
The previously applied rejections under 35 U.S.C. 112(a) and the previously applied objection to claim 1 have been withdrawn in view of applicant’s claim amendments on 5 December 2025.
Relevant Prior Art – No Rejection
The examiner has not rejected the instant claims on the grounds of anticipation or obviousness. The examiner has presented the following relevant prior art, and has explained why no rejection on the grounds of anticipation or obviousness has been set forth.
As relevant prior art, the examiner cites Pritchard et al. (US 2010/0196481 A1). Pritchard et al. (hereafter referred to as Pritchard) is drawn to a nanoparticle drug delivery system, as of Pritchard, title and abstract. Said drug delivery system may comprise bilirubin, as of Pritchard, paragraph 0051, wherein bilirubin is used as an antioxidant. While the primary embodiment of Pritchard is drawn to treating oxidative stress, Pritchard also teaches treating cancer, as of at least paragraph 0073. Example 2 of Pritchard on page 9 teaches that the nanoparticle comprises PLGA-PEG-PLGA. The skilled artisan would have been aware that PLGA, which refers to poly(lactic-co-glycolic) acid or poly(lactide-co-glycolide) is a hydrophobic polymer block and PEG, which refers to polyethylene glycol, is a hydrophilic polymer block.
Pritchard differs from the claimed invention because in Pritchard, the hydrophilic polymer (PEG) is bound to the hydrophobic polymer (PLGA), rather than being bound to a carboxyl group of the bilirubin. Nothing in Pritchard would have motivated the skilled artisan to have bound PEG to bilirubin instead of PLGA.
As additional relevant prior art, Ollinger et al. (Cell Cycle, Vol. 6:24, 2007, pages 3078-3085). Ollinger et al. (hereafter referred to as Ollinger) teaches that bilirubin inhibits tumor growth and induces cell cycle arrest, as of page 3078, title and abstract. Ollinger provides a study showing that bilirubin administration results in slower tumor growth in mice with tumors as compared with a control, as of Ollinger, page 3080, left column, figure 1B.
PNG
media_image2.png
390
564
media_image2.png
Greyscale
As such, Ollinger teaches that bilirubin significantly reduces tumor growth. This would have motivated the skilled artisan to have administered bilirubin to a patient suffering from cancer.
Olinger does not teach a bilirubin nanoparticle, and does not teach that the bilirubin is derivatized in the manner required by instant claim 1.
Even if, purely en arguendo, the skilled artisan would have been motivated to have combined Pritchard with Ollinger, this would not have resulted in the claimed invention. As best understood by the examiner, the combination of Pritchard with Ollinger would have resulted in a method of administering a polymer nanoparticle which encapsulates bilirubin and administering said nanoparticle to a patient suffering from cancer in an attempt to treat said cancer. However, this combination would not have read on the claimed invention. This is because, in a hypothetical combination of Pritchard in view of Ollinger, the hydrophilic polymer (PEG) would have been bound to the hydrophobic polymer (PLGA), rather than being bound to a carboxyl group of the bilirubin. Nothing in Pritchard or Ollinger would have motivated the skilled artisan to have bound PEG to bilirubin instead of PLGA.
Additionally, the instant claims require that the bilirubin nanoparticle encapsulates an anti-cancer agent. The skilled artisan would have been motivated to have combined an anti-cancer agent with the combination of Pritchard and Ollinger; however, the skilled artisan would not have expected that this would have resulted in the claimed invention. This is because the skilled artisan would have expected that the most likely result of the combination of Pritchard, Ollinger, and an additional anti-cancer agent would have been a nanoparticle wherein the bilirubin and additional-cancer agent are co-encapsulated in a polymer such as PLGA rather than a nanoparticle in which the additional anti-cancer agent is encapsulated in the bilirubin.
As an additional relevant reference, the examiner cites Kappas et al. (US Patent 5,010,073). Kappas et al. (hereafter referred to as Kappas) teaches the following, as of column 1, relevant text reproduced below.
PNG
media_image3.png
420
420
media_image3.png
Greyscale
Kappas teaches that bilirubin is neurotoxic, which would have motivated the skilled artisan against administering bilirubin to a patient as a therapeutic agent. While Kappas teaches that bilirubin di-glucoronide is not neurotoxic, the examiner notes that bilirubin di-glucoronide does not read on the claimed feature of bilirubin covalently bound to a hydrophilic polymer via a carboxyl group of the bilirubin. This is because the di-glucoronides of bilirubin are two separate sugars bound to bilirubin. These glucoronides do not comprise repeating units and therefore cannot be considered to be a hydrophilic polymer.
Non-Statutory 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 1-3 and 8-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,904,019. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a method of delivering an anti-cancer agent to a subject. This method entails administration of bilirubin nanoparticles comprising an encapsulated anti-cancer agent, wherein said bilirubin nanoparticles comprising bilirubin covalently bound to a hydrophilic polymer.
The conflicting claims are drawn to a bilirubin nanoparticle comprising bilirubin covalently bound to a hydrophilic polymer. Conflicting claim 5 recites encapsulating an anti-cancer agent in said nanoparticle.
The instant and conflicting claims differ because the conflicting claims are drawn to a composition whereas the instant claims are drawn to a method. Nevertheless, the skilled artisan would have been motivated to have administered the composition of the conflicting claims to a patient suffering from cancer. This is because conflicting claim 5 recites the inclusion of an anti-cancer agent. As such, the skilled artisan would have been motivated to have administered the composition of the conflicting claims to a patient suffering from cancer with a reasonable expectation of success because the composition of the conflicting claims comprises an anti-cancer agent.
Claims 1-3 and 8-12 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,571,486. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a method of delivering an anti-cancer agent to a subject. This method entails administration of bilirubin nanoparticles comprising an encapsulated anti-cancer agent, wherein said bilirubin nanoparticles comprising bilirubin covalently bound to a hydrophilic polymer.
The conflicting claims are drawn to fine particle comprising bilirubin, which the examiner understands to be a bilirubin nanoparticle. Said nanoparticle is conjugated to a hydrophilic polymer; the examiner understands the term “conjugated” to have essentially the same meaning as “covalently bound.” Conflicting claim 5 recites using an anti-cancer agent in said particle.
The instant and conflicting claims differ because the conflicting claims are drawn to a composition whereas the instant claims are drawn to a method. Nevertheless, the skilled artisan would have been motivated to have used the composition of the conflicting claims in a method of administering an anti-cancer agent to a subject suffering from cancer. This is because conflicting claim 5 recites the inclusion of an anti-cancer agent. As such, the skilled artisan would have been motivated to have administered the composition of the conflicting claims to a patient suffering from cancer with a reasonable expectation of success.
The instant and conflicting claims also differ because the conflicting claims recite a gas, which is not recited by the instant claims. However, in view of the “comprising” language recited by the instant claims, it is the case the instant claims do not exclude a gas. As such, the presence of a gas in the subject matter of the conflicting claims does not patentably differentiate the subject matter of the conflicting claims from that of the instant claims. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03(I).
Claims 1-3, 8-9, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,896,681 in view of Ollinger et al. (Cell Cycle, Vol. 6:24, 2007, pages 3078-3085).
Claims 1-3, 8-9, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,896,681 in view of Gruettner et al. (US 2005/0271745 A1).
The instant claims are drawn to a method of delivering an anti-cancer agent to a subject. This method entails administration of bilirubin nanoparticles comprising an encapsulated anti-cancer agent, wherein said bilirubin nanoparticles comprising bilirubin covalently bound to a hydrophilic polymer.
The conflicting claims are drawn to a bilirubin chelate complex conjugated with a hydrophilic molecule. Said hydrophilic molecule may be one of various polymers, as of conflicting claim 8. The composition of the conflicting claims comprises a superparamagnetic iron oxide or gold nanoparticle, as of conflicting claim 1.
The conflicting claims do not recite administration of the composition to a subject.
Ollinger et al. (hereafter referred to as Ollinger) teaches that bilirubin inhibits tumor cell growth, as of Ollinger, page 3078, title and abstract.
Gruettner et al. (hereafter referred to as Gruettner) is drawn to magnetic nanoparticle compositions, as of Gruettner, title and abstract. Said compositions are useful for treating cancer, as of Gruettner, Table 1, starting on page 6, as well as paragraphs 0069-0074.
It would have been prima facie obvious for one of ordinary skill in the art to have administered the composition of the conflicting claims to a subject suffering from cancer. The conflicting claims recite a nanoparticle composition comprising bilirubin particles, also comprising iron oxide particles. While the conflicting claims do not recite anti-cancer therapeutics, the skilled artisan would have understood that both bilirubin and iron oxide would have been useful for cancer treatment, as of both Ollinger and Gruettner respectively. As such, the skilled artisan would have been motivated to have administered the composition of the conflicting claims to a patient suffering from cancer with a reasonable expectation of success.
The instant and conflicting claims also differ because the conflicting claims recite a gold or iron oxide nanoparticle, which is not recited by the instant claims. However, in view of the “comprising” language recited by the instant claims, it is the case the instant claims do not exclude a gas. As such, the presence of a gold or iron oxide nanoparticle in the subject matter of the conflicting claims does not patentably differentiate the subject matter of the conflicting claims from that of the instant claims. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03(I).
This rejection does not apply to claims 10 and 12. This is because claims 10 and 12 are drawn to doxorubicin being the anti-cancer agent. This differs from the gold or iron oxide nanoparticle of the claims of the ‘681 patent.
Response to Arguments Regarding Double Patenting Rejections
The examiner previously presented rejections on the grounds of non-statutory double patenting, as of the prior office action mailed on 5 September 2025 (hereafter referred to as the prior office action). Applicant presented arguments regarding these rejections, as of applicant’s response on 5 December 2025 (hereafter referred to as applicant’s response). These arguments are addressed below.
As an initial matter, applicant makes the following argument on page 6 of applicant’s response, where relevant text is reproduced below.
PNG
media_image4.png
74
592
media_image4.png
Greyscale
The examiner disputes applicant’s position that this is an accurate summary of the policies related to non-statutory double patenting as set forth in the MPEP. In support of the examiner’s position, the examiner cites MPEP 804(I)(B)(3). This section of the MPEP states that 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 should be considered when making a nonstatutory double patenting analysis based on "obviousness."
Therefore, if the instant claims (which in this case are method claims) recite specific uses or functional limitations not recited by the conflicting claims (which in this case are composition claims), but modification of the subject matter of the conflicting claims to include these specific uses or functions would have been prima facie obvious, then there is a case of obviousness-type non-statutory double patenting.
Regarding the ‘019 patent, applicant then argues that the examiner has not identified a claim the ‘019 patent that recites the required method of delivering an encapsulated anti-cancer agent to a subject, as of applicant’s arguments, page 6, near bottom of page. It is the examiner’s position that even if, purely en arguendo, applicant’s argument is correct, it is still not persuasive to overcome the applied rejection. Claim 5 of the ’019 patent recites a bilirubin nanoparticle comprising a cargo that is an anti-cancer agent. While the claims of the ‘019 patent do not recite administering this nanoparticle to a patient having cancer. Nevertheless, the skilled artisan would have been motivated to have administered the preparation of claim 5 of the ‘019 patent to a subject having cancer, in order to have predictably had a therapeutic effect against the cancer with a reasonable expectation of success.
Regarding the previously applied rejection over the claims of the ‘486 patent, applicant makes the following argument.
PNG
media_image5.png
232
600
media_image5.png
Greyscale
This is not persuasive as it does not appear to accurately summarize the examiner’s position. The examiner did not take the position that the skilled artisan would have been motivated to have modified the composition recited by the claims of the ‘486 patent by removing the gas from the particles recited by the claims of the ‘486 patent. As such, applicant’s arguments appear to address a point that was not actually made by the examiner. In contrast, the examiner’s position was that the applied rejection on the grounds of non-statutory double patenting is proper even though the claims of the ‘486 patent recite a gas whereas the instant claims do not require a gas.
Additionally, the examiner also reiterates the point made above in regard to the double patenting rejection over the claims of the ‘019 patent. The examiner notes that claim 5 of the ‘486 patent recites loading of an anti-cancer drug in the nanoparticles. Therefore, the examiner takes the position that while conflicting claims do not recite administering this nanoparticle to a patient having cancer; nevertheless, the skilled artisan would have been motivated to have administered the preparation of claim 5 of the ‘486 patent to a subject having cancer, in order to have predictably had a therapeutic effect against the cancer with a reasonable expectation of success.
Regarding the double patenting rejection over the ‘681 patent, applicant makes the following arguments, as of page 9 of applicant’s response, relevant text reproduced below.
PNG
media_image6.png
98
600
media_image6.png
Greyscale
This is not persuasive. The skilled artisan would have understood that superparamagnetic iron oxide nanoparticles (SPION) and gold nanoparticles would themselves have been anti-cancer agents. This would have been known at the time of filing in view of the teachings of the secondary references Ollinger and Gruettner, which are cited on pages 21-22 of the prior office action.
Applicant then addresses this as of the last paragraph of page 9 of applicant’s response, which is reproduced below.
PNG
media_image7.png
144
598
media_image7.png
Greyscale
The examiner disputes that the instant claims require metal-free polymer-bilirubin nanoparticles. In contrast, the instantly claimed method does not exclude anti-cancer cargo that comprises metals. Additionally, Gruettner teaches that superparamagnetic nanoparticles are useful for cancer treatment as anti-cancer agents. As such, the skilled artisan would have understood that the composition of the claims of the ‘681 patent would have been expected to have had an anti-cancer therapeutic effect even if this was not recognized by the claims of the ‘681 patent.
Applicant then makes the following argument on page 10 of applicant’s response.
PNG
media_image8.png
126
594
media_image8.png
Greyscale
This is not persuasive as it does not appear to accurately summarize the examiner’s position. The examiner did not take the position that the skilled artisan would have been motivated to have discarded the metal the particles recited by the claims of the ‘681 patent. As such, applicant’s arguments appear to address a point that was not actually made by the examiner. In contrast, the examiner’s position was that the skilled artisan would have been motivated to have used the bilirubin nanoparticle comprising the metal containing architecture such as a superparamagnetic iron oxide particle for administration to a patient with cancer, in view of the teachings of secondary references Ollinger and Gruettner.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana (Sandy) Kaup can be reached at (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612