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 .
Election/Restrictions
Applicant’s election without traverse of Group II (claims 11-17 drawn to a method of treating an individual for cancer comprising administering said nanoparticle) in the reply filed on July 31, 2025 is acknowledged.
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 31, 2025.
Status of Claims
Claims 1-17 are currently pending. Claims 11-17 are under examination and claims 1-10 are withdrawn as set forth above.
Claim Interpretation
Pursuant to the Interview Summary attached, claim 11 is interpreted for the sake of prosecution as depending from only claim 1. Briefly, Applicant’s representative, Pamela Sherwood, clarified that the amendment to claim 11 filed 2/10/2023 was inadvertently omitted from the claim set filed July 31, 2025 (see Interview Summary).
Claims 16 and 17 recite functional outcomes of the method of claim 11, and are not directed to a positively recited step or a limitation on the subject, dose, nanoparticle, or administration route, etc. Thus, claims 16 and 17 are interpreted as properties necessarily (i.e. inherently) resultant from the method of claim 11. In other words, claims 16 and 17 recite an intended outcome as there are no positively recited limitations directed to measuring tumor growth or treatment effectiveness. Art teachings all positively recited limitations of the method of claim 11 is regarded as teaching all limitations of claims 16 and 17.
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 14-17 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.
Claims 14 and 16-17 recite “the method of claim 1.” However, claim 1 is a product and not a method, thus it is unclear whether claims 14-17 are directed to further limiting the product of claim 1 or should be interpreted as depending from claim 11. Some skilled artisan would argue that claims 14 and 16-17 fail to further limit the scope of the claim from which they depend. Other skilled artisan would argue that claims 14 and 16-17 are directed to the method of claim 11. For the purposes of applying prior art, claims 14 and 16-17 are interpreted with the scope of depending from claim 11. Claim 15 is rejected by virtue of dependency on claim 14.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16 and 17 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 16 and 17 recite intended functional outcomes of the method of claim 11, which are interpreted as inherent to the method (see Claim Interpretation as set forth above). Claims 16 and 17 fail to further limit the scope of claim 11, because they present no further positively recited limitations directed to methods steps, scope of the subject population, route of administration, dose, nanoparticle structure, and the like.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 11-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for relieving (i.e. causing regression of) cancer in an individual, does not reasonably provide enablement for the full scope of treating (i.e. including curing or preventing) an individual for cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“Treating” as recited in claim 11 is interpreted pursuant to the definition set forth in ¶ [0053] of the instant specification on pg. 12 as “administering an agent, or carrying out a procedure, for the purpose of obtaining an effect.” To this end, “obtaining an effect” is interpreted with the scope of obtaining any effect. Particularly, it is evident from the instant specification that the scope of the treating is contemplated as including prophylaxis, prevention, and curing the disease. However, there is no treatment that prevents or cures cancer known in the art and the specification does not enable to treat a subject with cancer commensurate in scope with prophylaxis, prevention, and curing.
“A specification may call for a reasonable amount of experimentation to make and use a patented invention. What is reasonable in any case will depend on the nature of the invention and the underlying art. Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023) (citing Minerals Separation Ltd. v. Hyde, 242 U.S. 261, 270-71 (1916)).” (MPEP 2164.01). In the instant case, the nature of preventing or curing cancer with a PEG-PLGA nanoparticle targeted to an immune checkpoint molecule encompasses administering the nanoparticle to subjects who may acquire cancer, which requires the ability to anticipate which subjects will ultimately develop cancer. Additionally, curing cancer encompasses completely eradicating and eliminating the disease and all likelihood of relapse.
Cancer is a highly heterogenous disease and no one person’s cancer is the same as another’s. The etiology of each cancer is complicated and poorly understood, and as a consequence the skilled artisan is generally unable to say in advance who will eventually develop cancer. Many potential factors have been hypothesized to cause a person to be at risk of, e.g., a brain tumor, only to be shown to have no predictive value in subsequent work (see, e.g., McKinney. J Neurol Neurosurg Psychiatry. 2004. 75(Suppl II):ii12–ii17, at pages ii15-16, cited herewith).
Hippisley-Cox and Coupland developed algorithms for predicting the risk of developing future cancer over a 10-year period with 11 different types of cancer using data on risk factors reported in patient’s electronic records (Hippisley-Cox and Coupland. 2015. BMJ Open. 5:e007825, cited herewith; see Introduction on pg. 2). Risk factors included general factors such as BMI, smoking status, alcohol use, as well as cancer-type specific factors including family history (pg. 3, left col). Even in the top 10% of women at the highest risk of cancer, the best performing algorithm, which compared to the literature had a “very good” performance, only had a sensitivity of 67% (Abstract, pg. 15, left col., and pg. 21, left col.).
Presently, pembrolizumab, the first anti-PD-1 treatments approved by the FDA, is indicated for unresectable, metastatic, recurrent, or advanced cancers (Keytruda® FDA Label. June, 2018. Retrieved from the Internet on August 14, 2025 from <URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s030lbl.pdf>). With respect to the use of immune checkpoint inhibitors in preventive medicine, Chen et al. found in a sample size of 10 mice that anti-PD-1 treatment of precancerous oral lesions delayed and/or reduced the number of tumors (Oncoimmunol. 2018. 7(2):e1388484, cited herewith; pg. 3-5 and Fig. 4), however, it studied a limited population and did not prevent malignancy from occurring. Thus, the art with respect to using PD-1 inhibitors to reverse the course of developing cancer is in its nascent stages of investigation.
While cancer prediction and prevention have been a long-sought after goal, the aforementioned art indicates a high level of unpredictability with respect to identifying whether an individual will develop cancer. Moreover, the use of immune checkpoint blockade in prevention of cancer, let alone diseases in general, is underdeveloped.
As long as the specification discloses at least one method for making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim, then the enablement requirement of 35 U.S.C. 112 is satisfied. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). (MPEP 2164.01(b)).
In the working examples (see pgs. 19-25) Applicants establish evidence that PD-L1 targeted PEG-PLGA nanoparticles delayed tumor growth in a murine MC38 colorectal carcinoma model (see ¶ [0097] on pg. 22 and Fig. 3). Clearly, delaying tumor growth is not commensurate with preventing or curing cancer. Thus, the instant specification fails to remedy the deficiencies in the art with respect to predicting which subject would acquire cancer and the efficacy of a PEG-PLGA nanoparticle targeted to an immune checkpoint molecule in stopping cancer from ever developing.
Rather, given the nature of the invention and underdevelopment of the art, one of ordinary skill would have to practice undue experimentation to practice the scope of preventing cancer with a PEG-PLGA nanoparticle targeted to an immune checkpoint molecule. Indeed, the skilled artisan would have to practice the full spectrum of translational research (in vitro mechanistic, animal models, preclinical and clinical trials, etc) to discover whether a PEG-PLGA nanoparticle targeted to an immune checkpoint molecule could prevent or cure a particular cancer. Thus, the amount of experimentation required to enable the invention as claimed goes beyond what the skilled artisan would consider as routine.
“Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC 1997).
“A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” (MPEP 2164.01(a)).
In view of the foregoing Wands analysis, claim 11 is rejected on the grounds that one of ordinary skill in the art would not be able to practice the full scope of treating (i.e. prophylaxis of, preventing, and curing) cancer in a subject administered the nanoparticle of instant claim 11. Claims 12-17 are rejected by virtue of their dependency.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 11, 12, 14, 16 and 17 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Goldberg in US 2018/0369407 A1 published December 27, 2018.
At ¶ [0141] through [0142] on pg. 18, Goldberg teaches covalently conjugating antibody Fab fragments including pembrolizumab and anti-PD-1 to nanoparticles comprising PEG-PLGA. Goldberg teaches administering intravenous administration of anti-PD1 PEG-PLGA nanoparticles in a murine subcutaneous model of MC38 colorectal carcinoma (¶ [0149] on pg. 19; ¶ [0166] through [0167] on pgs. 21-22; Fig. 35-36), as in instant claims 11, 12, and 14. Instant claims 16 and 17 are also anticipated by virtue of their inherency to the method of claim 11 (see Claim Interpretation above). Even so, Fig. 35A evidences reduced tumor growth relative to unconjugated antibody and Fig. 35B teaches extended time of survival, i.e. effectiveness.
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.
Claims 11-17 are rejected under 35 U.S.C. 103 as being unpatentable over Wang in US 2018/0282423 A1 published October 4, 2018, cited herewith, in view of Varshosaz et al. World J Gastroentrol. November 4, 2015. (42):12022-12041, cited herewith; as evidenced by Jin et al. Biomacromolecules. 2010. 1:2422-2431, cited herewith and Williamson et al. Cancer Chemother Pharmacol. April 23, 2015. 75:1075-1087, cited herewith.
Wang teaches a particle comprising at least two targeting agents, wherein the agent is an antibody fragment, and/or wherein the target is, inter alia, CTLA-4, PD-1, or LAG3 (see claims 1, 4, 5, 7, and 8; see also ¶ [0054] through [0064] on pg. 4). Wang teaches administering the particles intravenously or intraperitoneally and treating liver cancer (see claims 15 and 17; ¶ [0072] through [0074] on pg. 5; ¶ [0088] on pg. 6), relating to instant claims 12, 13, and 15. In Example 2, Wang teaches anti-OX40 and anti-PD1 are conjugated to maleimide-terminated PEG-PLGA nanoparticles, teaching the limitations of claim 11 directed to delivery of covalently linked PEG-PLGA nanoparticles.
While Wang teaches antibody fragments binding immune checkpoint molecules, conjugation to PLGA-PEG nanoparticles, intravenous and intraperitoneal administration, and treating liver cancer; Wang does not teach hepatocellular carcinoma.
However, Varshosaz summarizes the state of the art the time of instant filing with respect to treating hepatocellular carcinoma (HCC). Particularly, Varshosaz teaches that HCC is the 5th most common malignancy and the most common primary liver cancer (col. 1 in the first ¶ on pg. 12023). Varshosaz teaches targeted nanoparticles have gained attention as an efficient drug delivery system, which including homing via active targeting (Abstract on pg. 12022). PEG containing nanoparticles have particular advantages for reducing adhesive interactions and improved transport (see pg. 12027, col. 2., last ¶ through pg. 12030).
It would have been prima facie obvious to combine the teachings of Wang and Varshosaz arriving at treating a subject having hepatocellular carcinoma with an PEG-PLGA nanoparticle comprising anti-PD-1 fragment covalently attached for target therapeutic delivery. The skilled artisan would have been motivated by the explicit teachings of Wang on modulating the immune system with dual immune activating and checkpoint inhibiting PEG-PLGA nanoparticles, which are by Wang’s explicit teachings suggested for intraperitoneal delivery and treatment of liver cancer. In particular, the skilled artisan would have been motivated to select a subject having hepatocellular carcinoma because it is the most common form of liver cancer, as is taught by Varshosaz. Moreover, the skilled artisan would have had a reasonable expectation of success because Varshosaz evidences that targeted nanoparticles comprising PLGA and/or PEG are being developed for treating hepatocellular carcinoma. To this point, targeted PLGA-PEG nanoparticles via conjugation to antibody fragments for treating hepatocellular cancer was known in the art at the relevant time and within the level of skill (see Jin, e.g., in the Abstract). Moreover, provided that hepatocellular carcinoma is a peritoneal cancer, the person of ordinary skill would have found the intraperitoneal route of administration prima facie obvious as evidenced by both the explicit and implicit suggestions of Wang and the state of the art with respect to administering nanoparticles intraperitoneally for intraperitoneal cancers for the purpose of, e.g., overcoming the peritoneum-plasma barrier and minimizing systemic exposure to cytotoxic drugs (see Williamson on pg. 1076, particularly the second ¶ in col. 1). In conclusion, the skilled artisan, in view of the state of the art, would have been motivated to and had a reasonable expectation of success in combining the teachings of Wang and Varshosaz and arriving at treating hepatocellular carcinoma by administering PEG-PLGA nanoparticles conjugated to anti-PD-1 antibody fragments via intraperitoneal injection.
Claims 16 and 17 are rejected by virtue of the fact that all positively recited limitations of the method are prima facie obvious, thus the limitations direct to intended functional outcomes are necessarily met by the combination of Wang in view of Varshosaz as described above.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Mi et al. Cancer Res. 2017. 77(13_Suppl):978 teaches anti-OX40 and anti-PD1 conjugated to PLGA-PEG maleimide nanoparticles administered to murine melanoma models. Zale in WO 2017/137953 A1 published August 17, 2017 teaches combinations of nanoparticles with checkpoint inhibitor blockade.
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/B.K.S./Examiner, Art Unit 1644
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683