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 .
Claim Status
Applicant’s amendments and remarks, filed 02/06/2026, are acknowledged.
Claims 2, 7-9, 12, 15, 18, 21, 25-29, 34-35, 38-40, 42-45, 48-64, 66-69, 71, and 73-79 are canceled.
Claims 1, 3, 4, 6, 10, 13, 22, 30-33, 41, 46, 47, 65, 70, 72, and 80 are amended.
Claim 81 is new.
Claims 1, 3-6, 10-11, 13-14, 16-17, 19-20, 22-24, 30-33, 36-37, 41, 46-47, 65, 70, 72, and 80-81 are pending.
Claims 4-5, 17, 46-47, 65, 70, and 72 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 03/19/2025.
As such, claims 1, 3, 6, 10-11, 13-14, 16, 19-20, 22-24, 30-33, 36-37, 41, and 80-81 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Withdrawn Objections
The drawings objections are withdrawn. Issues regarding Figures 7, 12, and 17 have been sufficiently addressed through amendments to the drawings and specification on 02/06/2026.
The nucleic acid and amino acid sequence disclosure objection is withdrawn. The issue of the specification missing the incorporation by reference paragraph and sequences in the specification have been sufficiently addressed through amendments to the specification on 02/06/2026.
The specification objections are withdrawn. Issues regarding minor informalities and trademarks/names have been sufficiently addressed through amendments to the specification on 02/06/2026.
The claim objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the claims filed on 02/06/2026.
Withdrawn Rejections
Applicant’s arguments, see page 16, filed 02/06/2026, with respect to claim 13 rejected under 35 USC 112(d) as allegedly being of improper dependent form have been fully considered and are persuasive. The issue regarding improper dependent subject matter have been sufficiently addressed through amendments to the claim(s). As such, the rejection under 35 USC 112(d) is withdrawn.
Applicant’s arguments, see pages 16-18, filed 02/06/2026, with respect to claims 1-3, 6, 13, 22-24, 27-28, 30-33, and 41 rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive in part. Specifically, the issue regarding:
The term “of interest” in claims 1 and 2 is a relative term which renders the claim indefinite;
Claims 2 and 3 recite “a tumor antigen” and “a cancer-specific antigen”. It is unclear how these two types of antigens are different;
Claim 2 reciting a broad recitation followed by a narrower statement;
Claim 13 depends from a canceled claim. Thus, the scope of claim 13 is unclear;
In claim 22, the term “therapeutic or diagnostic antibody or fragment thereof” render the claim indefinite;
Claim 22 reciting a broad recitation followed by a narrower statement;
Claim 22 rejected on the basis that it contains an improper Markush grouping of alternatives;
Claim 29 reciting “at least one compound”;
The term “suppresses” in claims 30 and 31 is a relative term which renders the claim indefinite;
Claim 32 reciting “TGF-β inhibitor is a TGF-β receptor inhibitor”. These are two different target molecules;
Claim 33 reciting “LY2157299” within parentheticals;
Claim 35 reciting “an activator thereof”;
Claim 41 reciting a broad recitation followed by a narrower statement;
Claim 41 rejected on the basis that it contains an improper Markush grouping of alternatives;
Claim 41 reciting “malignant melanoma”; and,
Claim 80 reciting “the method of claim 9” but claim 9 refers to a composition
have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 2 and 27-28 are canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s remarks, see pages 18 and 19, filed 02/06/2026, with respect to claims 1-3, 6, 9-11, 13-14, 16, 19-24, 27-31, 36, 41, and 80 rejected under 35 USC 102 as allegedly anticipated by Ali et al (US 2017/0042995 A1, publication date: 02/16/2017) as evidenced by Shriver et al (Handb Exp Pharmacol. 2012; (207): 159-176) and claims 1-3, 6, 9-11, 13, 19-24, 29-32, 36, 41, and 80 rejected under 35 USC 102 as allegedly anticipated by Stephan (US 2016/0008399 A1, publication date: 01/14/2016) have been fully considered and are persuasive. Examiner acknowledges that claims 2, 9, 21, and 27-29 are canceled, thus rendering the rejection moot. Further, Examiner acknowledges claim 1 was amended to recite “a coating of membranes derived from an antigen presenting cell” which is not disclosed by the art. As such, the rejections under 35 USC 102 are withdrawn.
Applicant’s arguments, see pages 19 and 20, filed 02/06/2026, with respect to claims 1-3, 6, 9-11, 13-14, 16, 19-24, 27-37, 41, and 80 provisionally rejected on the grounds of nonstatutory double patenting of copending Application No. 17/638,519; claims 1-3, 6, 9-11, 13-14, 16, 19-24, 27-37, 41, and 80 provisionally rejected on the grounds of nonstatutory double patenting of copending Application No. 17/933,817; and, claims 1-3, 6, 9-11, 13-14, 16, 19-24, 27-37, 41, and 80 provisionally rejected on the grounds of nonstatutory double patenting of copending Application No. 18/719,643 have been fully considered and are persuasive. Examiner acknowledges claim 1 was amended to recite “A microparticle or nanoparticle comprising: (a) an antigen specific to a tumor cell or virus; (b) a coating of membranes derived from an antigen presenting cell; and (c) at least one compound that blocks induction of regulatory T cells (Tregs)” which is not disclosed by the copending applications. Further, Examiner acknowledges that claims 2, 9, 21, and 27-29 are canceled, thus rendering the rejection moot. As such, the provisional double patenting rejections are withdrawn.
New Objections Necessitated by Amendment
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (Figures 7 and 12 filed on 02/06/2026). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
New Rejections Necessitated by Amendment
Claim Rejections – 35 USC § 112(b)
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.
Claim 81 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05I. In the present instance, claim 81 recites the broad recitation “a lung carcinoma”, “renal cell carcinoma”, “lung cancer”, “Hodgkin’s lymphoma (HL)”, “non-Hodgkin’s lymphoma (NHL)”, and “bone neoplasms”, and the claim also recites “a small cell lung carcinoma”, “clear-cell metastatic renal cell carcinoma”, “non-small cell lung cancer (NSCLC)”, “squamous cell non-small cell lung cancer”, “advanced B-cell NHL”, “HL including diffuse large B-cell lymphoma (DLBCL)”, and “bone sarcoma”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Maintained Rejections
Claim Rejections – 35 USC § 112(b)
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.
Claim 6 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites “tumor sample” and “surgically obtained tumor, tumor biopsy”. It is unclear how these terms are different from each other. The claims nor the specification define these terms for one to understand how they are different.
Applicant’s Arguments
Applicant amended claim 6 to retain tumor and tumor sample. (see pages 17 and 18 of the Remarks filed on 02/06/2026).
Response to Arguments
Applicant’s arguments filed 02/06/2026 have been fully considered but they are not persuasive. Examiner acknowledges the amendments to the claims. However, with respect to claim 6, it remains unclear how these terms are different as the claims nor specification define these terms. Therefore, the 112(b) rejection is maintained.
Claim Rejections – 35 USC § 112(a) Written Description
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 1, 3, 6, 10-11, 13-14, 16, 19-20, 22-24, 30-33, 36–37, 41, and 80-81 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 1 is drawn to a microparticle or nanoparticle comprising: (a) an antigen specific to a cell or virus; (b) a coating of membranes derived from an antigen presenting cell; and (c) at least one compound that blocks induction of regulatory T cells (Tregs).
Claim 3 is drawn to the microparticle or nanoparticle of claim 1, wherein the antigen specific to a tumor cell comprises a membrane isolated from the tumor cell or from a tumor tissue comprising the tumor cell.
Claim 6 is drawn to the microparticle or nanoparticle of claim 1, wherein the tumor is obtained from a surgically obtained tumor or tumor sample.
Claim 10 is drawn to the microparticle or nanoparticle of claim 1, wherein the antigen presenting cell is stimulated in vitro before the membrane is isolated.
Claim 11 is drawn to the microparticle or nanoparticle of claim 1, wherein the microparticle or nanoparticle comprises a polymer.
Claim 13 is drawn to the microparticle or nanoparticle of claim 11, wherein the polymer is alginate, hyaluronic acid, or chitosan.
Claim 14 is drawn to the microparticle or nanoparticle of claim 1, wherein the microparticle or nanoparticle further comprises heparin.
Claim 16 is drawn to the microparticle or nanoparticle of claim 11, wherein the polymer is cross-linked.
Claim 19 is drawn to the microparticle or nanoparticle of claim 1, further comprising at least one immunoregulatory compound.
Claim 20 is drawn to the microparticle or nanoparticle of claim 19, wherein the at least one immunoregulatory compound comprises an immunostimulatory compound.
Claim 22 is drawn to the microparticle or nanoparticle of claim 19, wherein the at least one immunoregulatory compound comprises a cytokine.
Claim 23 is drawn to the microparticle or nanoparticle of claim 22, wherein the cytokine comprises an interleukin (IL) or stromal cell-derived factor 1a (SDF-1a).
Claim 24 is drawn to the microparticle or nanoparticle of claim 23, wherein the interleukin comprises interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-10 (IL-10), interleukin-12 (IL-12), or interleukin-15(IL-15) or an IL-2 superkine.
Claim 30 is drawn to the microparticle or nanoparticle of claim 1, wherein the at least one compound that blocks induction of Tregs is loaded onto β-cyclodextrin conjugated to the microparticle or nanoparticle.
Claim 31 is drawn to the microparticle or nanoparticle of claim 1, wherein the compound that blocks induction of Tregs comprises a TGF-β inhibitor.
Claim 32 is drawn to the microparticle or nanoparticle of claim 1, wherein the compound that blocks induction of Tregs is a TGF- β receptor inhibitor.
Claim 33 is drawn to the microparticle or nanoparticle of claim 31, wherein the TGF-β inhibitor is galunisertib or SB505124.
Claim 36 is drawn to the microparticle or nanoparticle of claim 1, further comprising a small molecule.
Claim 37 is drawn to the microparticle or nanoparticle of claim 1, further comprising a hydrophobic therapeutic agent.
Claim 41 is drawn to the microparticle or nanoparticle of claim 1, wherein the tumor antigen is specific for a tumor comprising a sarcoma, a carcinoma, a breast cancer or tumor, an ovarian cancer or tumor, a prostate cancer or tumor, a cervical cancer or tumor, a uterine cancer or tumor, a testicular cancer or tumor, a glioma, a melanoma, pancreatic cancer, bladder cancer, stomach cancer, fibrotic cancer, glioma, kidney cancer, lung cancer, chronic myeloid leukemia, colorectal cancer, or colon cancer.
Claim 80 is drawn to the microparticle or nanoparticle of claim 1, wherein the antigen presenting cell comprises a B cell, a macrophage, a dendritic cell, a T cell or a natural killer (NK) cell.
Claim 81 is drawn to the microparticle or nanoparticle of claim 1, wherein the tumor antigen is specific for a tumor comprising a fibrosarcoma, a myxosarcoma, a liposarcoma, a chondrosarcoma, an osteogenic sarcoma, a chordoma, an angiosarcoma, an endotheliosarcoma, a lymphangiosarcoma, a lymphangioendotheliosarcoma, a synovioma, a mesothelioma, an Ewing’s tumor, a leiomyosarcoma, a rhabdomyosarcoma, a colon carcinoma, a squamous cell carcinoma, a basal cell carcinoma, an adenocarcinoma, a sweat gland carcinoma, a sebaceous gland carcinoma, a papillary carcinoma, a papillary adenocarcinomas, a cystadenocarcinoma, a medullary carcinoma, a bronchogenic carcinoma, a renal cell carcinoma, a hepatoma, a bile duct carcinoma, a choriocarcinoma, a seminoma, an embryonal carcinoma, a Wilm’s tumor, a lung carcinoma, a small cell lung carcinoma, a bladder carcinoma, an epithelial carcinoma, a glioma, an astrocytoma, a medulloblastoma, a craniopharyngioma, an ependymoma, a pinealoma, a hemangioblastoma, an acoustic neuroma, an oligodendroglioma, a schwannoma, a meningioma, a neuroblastoma, or a retinoblastoma, esophageal cancer, metastatic pancreatic cancer, metastatic adenocarcinoma of the pancreas, malignant glioma, diffuse intrinsic pontine glioma, recurrent childhood brain neoplasm, renal cell carcinoma, clear-cell metastatic renal cell carcinoma, metastatic castration resistant prostate cancer, stage IV prostate cancer, metastatic melanoma, recurrent melanoma of the skin, melanoma brain metastases, stage IIIA skin melanoma; stage IIIB skin melanoma, stage IIIC skin melanoma; stage IV skin melanoma, melanoma of head and neck, lung cancer, non-small cell lung cancer (NSCLC), squamous cell non-small cell lung cancer, recurrent metastatic breast cancer, hepatocellular carcinoma, Hodgkin’s lymphoma (HL), follicular lymphoma, non-Hodgkin’s lymphoma (NHL), advanced B-cell NHL, HL including diffuse large B-cell lymphoma (DLBCL), multiple myeloma, adult acute myeloid leukemia in remission; adult acute myeloid leukemia with Inv(16)(p13.1q22); CBFB-MYH11; adult acute myeloid leukemia with t(16;16)(p13.1;q22); CBFB-MYH11; adult acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNX1T1; adult acute myeloid leukemia with t(9;11)(p22;q23); MLLT3-MLL; adult acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA; alkylating agent-related acute myeloid leukemia, chronic lymphocytic leukemia, Richter’s syndrome; Waldenstrom’s macroglobulinemia, adult glioblastoma; adult gliosarcoma, recurrent glioblastoma, recurrent childhood rhabdomyosarcoma, recurrent Ewing sarcoma/ peripheral primitive neuroectodermal tumor, recurrent neuroblastoma; recurrent osteosarcoma, MSI positive colorectal cancer; MSI negative colorectal cancer, nasopharyngeal nonkeratinizing carcinoma; recurrent nasopharyngeal undifferentiated carcinoma, cervical adenocarcinoma; cervical adenosquamous carcinoma; cervical squamous cell carcinoma; recurrent cervical carcinoma; stage IVA cervical cancer; stage IVB cervical cancer, anal canal squamous cell carcinoma; metastatic anal canal carcinoma; recurrent anal canal carcinoma, recurrent head and neck cancer; head and neck squamous cell carcinoma (HNSCC), ovarian carcinoma, advanced GI cancer, gastric adenocarcinoma; gastroesophageal junction adenocarcinoma, bone neoplasms, soft tissue sarcoma; bone sarcoma, thymic carcinoma, urothelial carcinoma, recurrent Merkel cell carcinoma; stage III Merkel cell carcinoma; stage IV Merkel cell carcinoma, myelodysplastic syndrome, recurrent mycosis fungoides or Sezary syndrome.
The specification discloses of generating microparticles by microfluidic droplet generation using alginate-heparin as the main component (see [243]). The alginate was crosslinked using a 4-arm PEG hydrazide cross linker (see [243]). By varying the amount of crosslinker, the particles can be made mechanically soft or stiff; by changing the polymer concentration, the 4-arm PEG hydrazide concentration and the calcium concentration, the mechanical stiffness of the microparticle is tunable (see [244]). To promote T cell activation, the stimulatory cytokine IL-2 is loaded in the particles for uptake and later, passive release (see [245]). Fig. 4 shows that by including heparin in the microparticle formulation, more IL-2 can be retained by the particles and released more slowly (see [245]). The specification discloses of B cells were activated in vitro and lysed where the membranes were collected after centrifugation and incubated with the alginate-heparin microparticles (see [247]). The B cells and the microparticles showed that they have plentiful expression of the cell-surface adhesion molecule ICAM-1, the antigen presenting molecule MHC-II, and the costimulatory ligand B7-1 (CD80) (see [247] and Fig. 8). The specification discloses that the alginate-heparin microparticles have a greater affinity for TGF-β and a higher binding efficiency (see [252]). The specification also discloses that for anti-cancer utilities of the microparticles, induction of Tregs is undesirable (see [252]).
To efficiently stimulate the proliferation of cytotoxic T cells, the microparticles should suppress formation of Tregs from CD4+ cells attracted to the microparticles (see [253]). Galunisertib showed higher degree of Tregs suppression as evaluated based on Foxp3 expression (see Fig. 16). Incorporation of β-cyclodextrin was used to increase the affinity and loading of galunisertib to microparticles (see Fig. 17). Β-cyclodextrin was conjugated to alginate or alginate-heparin polymers, and Figs. 18 and 19 depicted the strong affinity of galunisertib towards β-cyclodextrin (see [253]-[254]). Fig. 22 depicts the effect of microparticle mechanical properties of B-cell membrane microparticles treated with SIINFEKL (SEQ ID NO: 1) (ovalbumin peptide) and cultured with naïve OT-I T cells prepared by negative selection from mouse spleens ex vivo (see [256]). In a B16 melanoma mouse model, T cells activated by microparticles cleared the tumors better than even DYNABEAD™-activated OT-Is (see [259] and Figs. 27-29). Fig. 34 demonstrates that microparticles coated with both B cell and B16-F10-Ova melanoma cell membranes reduced tumor mass compared to B cell membrane-coated microparticles with or without Ova-peptide loaded (see [263]-[264]).
However, the specification fails to disclose that Applicant was in possession of the claimed microparticles or nanoparticles. Specifically, the specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles comprising any antigen specific to any cell or virus of interest and any costimulatory component derived from any antigen presenting cell. The specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles, and has not adequately described the enormous genera of antigens that are required by the claims. The specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles comprising any polymer. The specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles further comprising any immunoregulatory compound. The specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles further comprising any compound that regulates induction of Tregs. Lastly, the specification fails to disclose that Applicant was in possession of the large genera of microparticles or nanoparticles comprising the genera of therapeutic or diagnostic antibodies, TGF-beta or TGF-beta receptor inhibitors, activators of Tregs or TGF-beta, or further comprising any hydrophobic therapeutic agent or any small molecule.
Although the specification discloses of β-cyclodextrin conjugated to alginate-heparin microparticles treated with SIINFEKL and coated with both B cell and B16-F10-Ova melanoma cell membranes, the claims are not limited to these microparticles, and are inclusive of any microparticle or nanoparticles comprising any antigen specific to any cell or virus of interest and any costimulatory component derived from any antigen presenting cell. This indicates that there are hundreds, if not thousands, of possible microparticles or nanoparticles encompassed by the claims. Thus, the claims encompass a vast genus of microparticles or nanoparticles that have the claimed functions. However, the specification provides limited guidance on the structure and steps required for maintaining the claimed function(s). Therefore, the specification does not provide adequate written description to identify the broad and variable genus of microparticles or nanoparticles because, inter alia, the specification does not disclose a correlation between the necessary structure of the costimulatory component derived from an antigen presenting cell and immunoregulatory compound, and the function(s) recited in the claims; and thus, the specification does not distinguish the claimed genus from others, except by function. Although the term antibody does impart some structure, the structure that is common to antibodies is generally unrelated to its specific binding function; therefore, correlation is less likely for antibodies than for other molecules. Accordingly, the specification does not define any structural features commonly possessed by the members of the genus, because while the description of an ability of the claimed substance may generically describe the molecule’s function, it does not describe the substance itself. A definition by function does not suffice to define the genus because it is only an indication of what the substance does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves the result. In addition, because the genus of substances is highly variable (i.e. each substance would necessarily have a unique structure, See MPEP 2434), the generic description of the substance is insufficient to describe the genus. Further, given the highly diverse nature of antibodies, particularly in CDRs, even one of skill in the art cannot envision the structure of an antibody by only knowing its binding characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of antibodies/compounds and variants thereof claimed only be a functional characteristic(s) and/or partial structure.
A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not sufficient identifying characteristics for written description purposes, even when accompanied by a method of obtaining the agent. The specification does not adequately describe the correlation between the chemical structure and function of the genus, such as structural domains or motifs that are essential and distinguish members of the genus from those excluded. Thus, the genus of antibodies has no correlation between their structure and function.
MPEP § 2163.03(V) states:
While there is a presumption that an adequate written description of the claimed invention is present in the specification as filed, In re Wertheim, 541 F.2d 257, 262, 191 USPQ 90, 96 (CCPA 1976), a question as to whether a specification provides an adequate written description may arise in the context of an original claim. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. “Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Applicant has not shown possession of a representative number of species of microparticles or nanoparticles. The disclosure of only one or two species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”) (MPEP 2163).
The instant claims do not fully describe the structure of the immunoregulatory compound to achieve the required function. Accordingly, the specification also does not provide adequate written description to identify the broad genus of microparticles or nanoparticles, claimed only by a function characteristic(s) and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous microparticles or nanoparticles had not yet been identified and thus, the specification represents little more than a wish for possession. Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of microparticles or nanoparticles claimed only by a partial structure and functional characteristic(s). Thus the microparticles or nanoparticles described by the instant claims encompasses an overly broad genus, the structure of costimulatory component derived from an antigen presenting cell and immunoregulatory compound, and the functional outcome.
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361). An adequate written description must contain enough information about the actual makeup of the claimed products — “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). Most significant to the present case, the Court held that “knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies” (Amgen at 1361). The idea that written description of an antibody can be satisfied by the disclosure of a newly-characterized antigen “flouts basic legal principles of the written description requirement” as it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen... And Congress has not created a special written description requirement for antibodies” (Amgen at page 1362).
Abbvie v. Centocor (Fed. Cir. 2014) is also relevant to the instant claims. In Abbvie, the Court held that a disclosure of many different antibodies was not enough to support the genus of all neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The instant case has many similarities to AbbVie above. First, the claims clearly attempt to define the genus of compounds that regulates induction of Tregs by the functions of suppressing induction of Tregs or induces of Tregs. As noted by AbbVie above, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description. Second, there is no information in the specification based upon which one of skill in the art would conclude that the disclosed species for which applicant has identified as having the recited functions would be representative of the entire genus. The specification discloses no structure to correlate with the function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim.
Furthermore, regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.)
Further, the skilled artisan cannot envision the detailed chemical structure of the encompassed microparticles or nanoparticles, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ... To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
Regarding the encompassed compounds that are antibodies, the functional characteristics of antibodies (including binding specificity and affinity are dictated on their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416; previously submitted with the Office Action mailed on 09/18/2025) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site.” The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2; previously submitted with the Office Action mailed on 09/18/2025), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
The claims encompass an extremely large number of possible compounds that have specific required functions. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies/therapeutic agents or a sufficient structure-function correlation to meet the written description requirements.
Regarding the encompassed compounds that are proteins and peptides, protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutation will have on a protein (such as TNF or a cytokine) as taught by Skolnick et al. (Trends Biotechnol. 2000 Jan;18(1):34-9; previously submitted with the Office Action mailed on 09/18/2025), sequence-based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g. abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g. abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cell (see e.g. page 34, right column). Skolnick advocates determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g. page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990; previously submitted with the Office Action mailed on 09/18/2025) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988; previously submitted with the Office Action mailed on 09/18/2025) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98; previously submitted with the Office Action mailed on 09/18/2025) teach that Short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g. page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g. page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g. page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g. page E5197, left column, top paragraph). Additionally, Bork (Genome Research, 2000,10:398-400; previously submitted with the Office Action mailed on 09/18/2025) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
One key issue is the prediction of protein function based on sequence similarity, which could be one way to identify the functional proteins that are useful in the instant claims. Kulmanov et al (Bioinformatics, 34(4), 2018, 660–668; previously submitted with the Office Action mailed on 09/18/2025), teach that there are key challenges for protein function prediction methods (see e.g. page 661, left column). These challenges arise from the difficulty identifying and accounting for the complex relationship between protein sequence structure and function (see e.g. page 661, left column). Despite significant progress in the past years in protein structure prediction, it still requires large efforts to predict protein structure with sufficient quality to be useful in function prediction (see e.g. page 661, left column). Another challenge is that proteins do not function in isolation. In particular higher level physiological functions that go beyond simple molecular interactions will require other proteins and cannot usually be predicted by considering a single protein in isolation (see e.g. page 661, left column). Due to these challenges it is not obvious what kinds of features should be used to predict the functions of a protein and whether they can be generated efficiently for a large number of proteins, such as the vast genus of proteins and peptides that may be encompassed by the instant claims (see e.g. page 661, left column).
The state of the art regarding the structure-function correlation cannot be relied upon because functional characteristics of any peptide/protein are determined by its structure as evidenced by Greenspan et al. 1999 (Defining epitopes: It’s not as easy as it seems; Nature Biotechnology, 17:936-937; previously submitted with the Office Action mailed on 09/18/2025). Greenspan et al. teach that as little as one substitution of an amino acid (e.g. alanine) in a sequence results in unpredictable changes in the 3-dimenstional structure of the new peptide sequence which, in turn, results in changes in the functional activity such as binding affinity of the peptide sequence (page 936, 1st column). Greenspan et al. teach that contribution of each residue (i.e. each amino acid) cannot be estimated with any confidence if the replacement affects the properties of the free form of the molecule (page 936, 3rd column).
Given not only the teachings of Skolnick et al., Lazar et al., Burgess et al., and Greenspan et al., but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the claimed compounds could not be predicted based on sequence identity. Clearly, it could not be predicted that a polypeptide or a variant that shares only partial homology with a disclosed protein or that is a fragment of a given SEQ ID NO. will function in a given manner.
Regarding compounds that are small molecules of a particular protein target, the prediction of binding to a target, much less the inhibitory activity, is highly unpredictable. According to Guido et al. (Curr Med Chem. 2008;15(1):37-46; previously submitted with the Office Action mailed on 09/18/2025), accurately predicting the binding affinity of new drug candidates remains a major challenge in drug discovery (see page 37). There are a vast number of possible compounds that may bind any particular target, many of which have likely not been discovered. Relying on virtual screening also lends unpredictability to the art regarding identification of molecules that would be capable of the required functions of the instant claims. Guido et al. teach that there are two main complex issues with predicting activity for a small molecule: accurate structural modeling and/or correct prediction of activity (see page 40). As taught by Clark et al. (J. Med. Chem., 2014, 57 (12), pp 5023–5038; previously submitted with the Office Action mailed on 09/18/2025), even when guided by structural data, developing selective structure-activity relationships has been challenging owing to the similarities of the enzymes (see page 5028). Therefore, it is impossible for one of skill in the art to predict that any particular encompassed small molecule therapeutic would function to inhibit a particular protein, especially a particular protein family member, or treat disease.
Regarding compounds that are nucleic acid-based therapeutics, the efficacy of any possible DNA or RNA based therapeutic modality is highly unpredictable. This unpredictability stems from an inability to predict the effects of any particular sequence the expression or function of any target. As taught by Aagaard et al. (Advanced Drug Delivery Reviews 59 (2007) 75–86; previously submitted with the Office Action mailed on 09/18/2025), the development of RNAi based therapeutics faces several challenges, including the need for controllable or moderate promoter systems and therapeutics that are efficient at low doses (see page 79), the ability of an unpredictable number of sequences to stimulate immune responses, such as type I interferon responses (see page 79), competition with cellular RNAi components (see page 83), the side effect of suppressing off targets (see page 80), and challenging delivery (see page 83). The success of antisense strategies, including anti-RNA and anti-DNA strategies are also highly unpredictable. Warzocha et al. (Leukemia and Lymphoma (1997) Vol. 24. pp. 267-281; previously submitted with the Office Action mailed on 09/18/2025) teach that the efficacy of antisense effects varies between different targeted sites of RNA molecules and three-dimensional RNA structures (see page 269), while DNA-targeting strategies have numerous problems including a restricted number of DNA sequences that can form triple helices at appropriate positions within genes and the inaccessibility of particular sequences due to histones and other proteins (see page 269). These references demonstrate that variation in RNA or DNA based therapeutics will often dramatically affect the biological activity and characteristics of the intended therapeutic. McKeague et al. (J Nucleic Acids. 2012;2012:748913. Epub 2012 Oct 24; previously submitted with the Office Action mailed on 09/18/2025) teach that aptamers have particular challenges because unlike antibodies or molecular imprinted polymers, their tertiary structure is highly dependent on solution conditions and they are easily degraded in blood. Further, they have less chemical diversity than other antagonist molecules (see page 2), and have issues associated with determining the Kd measurements for a given molecule (see page 13).
Given the teachings of Aagaard et al, Warzocha et al, and McKeague et al, the claimed nucleic acid therapeutics could not be predicted based on the targets selected or similarities to the disclosed example therapeutics. Therefore, it is impossible for one of skill in the art to predict that any particular encompassed nucleic acid based therapeutic, such as oligonucleotide aptamers, RNAi molecules and antisense oligonucleotides, would function to decrease expression or function of a target gene or protein, or treat disease.
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function (see MPEP 2163). A patent specification must set forth enough detail to allow a person of ordinary skill in the art to understand what is claimed and to recognize that the inventor invented what is claimed. In the case of DNA or amino acids, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention (see Lilly, 119 F.3d at 1566 (quoting Fiers, 984 F.2d 15 1171 ). Because the specification does not describe the amino acid sequences nor any core structures for potentially numerous different antibody amino acid sequences which would have the recited dissociation constant, one of skill in the art would reasonably conclude that applicant was not in possession of the claimed genus of all compounds.
A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies.
While “examples explicitly covering the full scope of the claim language” typically will not be required, a sufficient number of representative species must be included to “demonstrate that the patentee possessed the full scope of the [claimed] invention.” Lizard tech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724,1732 (Fed. Cir. 2005).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the claimed microparticles or nanoparticles. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features (see, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916,927, 69 USPQ2d 1886, 1895 (Fed. Cir. 2004); accord Ex Parte Kubin, 2007-0819, BPAI 31 May 2007, opinion at p. 16, paragraph 1). The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116).
Without an adequate structural description of the claimed components and descriptive support on how to put them together, one of ordinary skill in the art would not be reasonably apprised that Applicant was in possession of the genera of microparticles or nanoparticles as claimed. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Applicant’s Arguments
Applicant respectfully traverses the rejection in light of the amendments to the claims and ensuing remarks. While not agreeing with the propriety of the rejection, to expedite examination, Applicant amended the claims to focus on a microparticle or nanoparticle comprising a tumor cell antigen or a viral antigen, having a coating of an APC membrane, and a compound that blocks induction of Tregs. Applicant asserts that such components provide the specificity and scope of the claims in compliance with the written description rules. Withdrawal of the rejection is requested. (see page 18 of the remarks filed on 02/06/2026).
Response to Arguments
Applicant’s arguments filed 02/06/2026 have been fully considered but they are not persuasive. Examiner acknowledges the amendments to the claims; however, the amendments do not overcome the rejection because the claims describe components of the microparticles or nanoparticles without providing a structure. While Applicant is entitled to use functional language in the description of claimed agents, according to MPEP 2163, an invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. This matches the facts here. The claims require specific functionality for the components of the microparticle or nanoparticle, but the instant disclosure does not provide description of the corresponding structure for that functionality or a representative number of species for the agents/components. For example, the antigen specific to a tumor cell or virus is defined by a large genus of cancers recited in claims 41 and 81, and the compound that blocks induction of Tregs are also defined by their ability to inhibit TGF-beta. In both the base claims and the dependent claims, for at least one agent/component in each claim, the claims only describe what the agent/component does, not what the agents/components are. While the agent/component of the microparticle or nanoparticle that galunisertib or SB505124 is described as long as there are no additional functional requirements like those found in the dependent claims, the antigen specific to a tumor cell or virus or the coating of membranes derived from an antigen presenting cell is not defined in any way, except for its functional properties. While methods to identify compounds with the required function may be routine in the art, the fact that any experimentation is required to figure out exactly what is encompassed necessarily means that applicant has not sufficiently described the claimed subject matter.
There are thousands of possible microparticles or nanoparticles encompassed by the instant claims. One of skill in the art could not immediately envisage the encompassed species in each genus from the guidance provided in the instant specification and claims. Applicant has supplied examples of components of the claimed microparticles or nanoparticles, the claims are not limited to this species. The claims encompass all antigens, all compounds that inhibit induction of Tregs, and a coating of any membrane derived from any antigen presenting cell. This encompasses an extremely broad genus of compounds with a specific function, for which no correlating structure is provided. While one of skill in the art could likely screen for said compounds and antibodies, the mere fact that experimentation is necessary to identify the members of the genus indicates that proper description has not been provided.
The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 “merely by clearly describing one embodiment of the thing claimed.” LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005). Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’ s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product; however, the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
Specifically addressing the TGF-beta inhibitors that may be antibodies, the Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself even when preparation of such an antibody would be routine and conventional. Amgen Inc., v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies. In the instant application, neither the art nor the specification provides a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Further, arguments relating to the isolation of an antibody with specific characteristics may be more appropriately directed to the invention’ s enablement, since the method of isolating would detail how to make the invention. However, the enablement of the invention has not been rejected by the Examiner.
As such, the written description rejection is maintained.
Claim Rejections – 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Cheung et al
Claims 1, 3, 10-11, 13, 19-20, 22-24, 41, and 80-81 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheung et al (Nat Biotechnol. 2018 February ; 36(2): 160–169).
With respect to claims 1, 3, 10, 19-20, 22-24, 41, and 80-81, Cheung et al disclose of a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid biolayer supported by mesoporous silica micro-rods (see Abstract). The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and co-stimulation, while the micro-rods enable sustained release of soluble paracrine cues (see Abstract). Using anti-CD3, anti-CD28, and interleukin-2, Cheung et al show that the APC-mimetic scaffolds (APC-ms) promote two- to ten-fold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads) (see Abstract). APC-ms support over 5-fold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with similar efficacy in a xenograft lymphoma model (see Abstract). Particularly, Cheung et al demonstrate antigen-specific expansion of primary human T cells in vitro from donor leukapheresis samples and from PBMCs wherein enrichment of live CD8+ cells specific for peptides CLGGLLTMV (CLG; a) and GLCTLVAML (GLC; c) (EBV-derived peptides) (see pgs. 5-6 and 11-14; Figures 1, 4, and 5). Cheung et al disclose that isolated primary mouse and human T cells were mixed with activation stimuli (i.e., Dynabeads or APC-ms), and cultured for up to two weeks (see pg. 12). Cheung et al disclose that APC-ms formulations were benchmarked against commercial CD3/CD28 T cell expansion beads (Dynabeads) for the polyclonal expansion of primary mouse T cells isolated from C57BL/6J mice (see pg. 4). Cheung et al found that no expansion of CD4+ FoxP3+ regulatory T cells was observed with either Dynabeads or APC-ms (see page 4). Additionally, Cheung et al investigated wither APC-ms would enable antigen-specific expansion of primary mouse CD8+ T cells by replacing anti-CD3 with a biotinylated H-2K(b) MHC class I monomer presenting SIINFEKL to afford the antigen-specific expansion of OT-1 cells (see page 5). When cultured with B16-F10 melanoma cells pulsed with SIINFEKL (an ovalbumin-derived peptide), the expanded T cells recognized their cognate antigen and secreted IFNγ and killed target cells in vitro (see page 5; Fig. 4c; Fig. 4e). Further, Cheung et al disclose that cytokine (IL-2, IL-21, and TGF-beta) loading and release was quantified by loading 500 µg of MSRs with 2 µg of the specified cytokine followed by coating with lipid as described (see pg. 11). Cheung et al show that presenting T cell stimuli across the surface of a fluid lipid bilayer, emulating how these cues are presented on an APC plasma membrane, relatively lower surface cue densities can promote more rapid expansion rates and generate T cells with a more functional and less exhausted phenotype (see pg. 8). Cheung et al disclose that by presenting T cell stimuli across the surface of a fluid lipid bilayer, emulating how these cues are presented on an APC plasma membrane, relatively lower surface cue densities can promote more rapid expansion rates and generate T cells with a more functional and less exhausted phenotype (see pg. 8).
With respect to claims 11 and 13, Cheung et al disclose that the micro-rods were synthesized comprising Pluronic P123 surfactant (average Mn ~5,800) was dissolved in 1.6 M HCl solution and stirred with tetraethyl orthosilicate (see pg. 10).
As such, the teachings of Cheung et al anticipate the present invention.
Mooney (US 2019/0216910 A1)
Claims 1, 3, 6, 10-11, 13-14, 16, 19-20, 22-24, 30-33, 36-37, 41, and 80-81 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mooney et al (US 2019/0216910 A1, publication date: 07/18/2019) as evidenced by Shriver et al (Handb Exp Pharmacol. 2012; (207): 159–176).
With respect to instant claims 1, 3, 6, 10, 19-20, 22-24, 36, 41, and 80-81, Mooney et al disclose of methods and compositions for eliciting an immune response to an antigen, such as cancer and microbial antigens (see Abstract, [0022], and [0047]). Particularly, Mooney et al disclose of a device comprising a delivery vehicle comprising a scaffold composition and any combination of one or more of the following compounds: (a) at least one antigen; (b) at least one immunostimulatory compound; (c) at least one compound that attracts an immune cell to or into the delivery vehicle; (d) at least one compound that induces immunogenic cell death of a tumor cell; I at least one compound that inhibits T-cell or dendritic cell suppression; and/or (f) at least one compound that inhibits an immune-inhibitory protein (see [0006]). Mooney et al also disclose that the claimed invention further comprises one or more of (i) an immunostimulatory compound, (ii) a compound that causes immunological cell death of a tumor cell, (iii) a compound that inhibits T cell or dendritic cell suppression, (iv) a compound that inhibits an immune-inhibitory protein, and (v) a cytokine (e.g., a chemoattractant of immune cells, such as dendritic cells) (see [0060]). Mooney et al disclose that the compound that inhibits T cell or dendritic cell suppression is a TGF-beta inhibitor (see [0061]). Mooney et al disclose that the scaffold comprises a cytokine comprises a cytokine such as GM-CSF, Flt3L, XCL1, IL-2, or IL-12 (see [0061]). Additionally, Mooney et al disclose that the immune cell comprises a macrophage, T-cell, B-cell, NK cell, or dendritic cell (see [0044]). Mooney et al disclose of obtaining the tumor cell or tumor tissue from the tumor mass itself (see [0057]). Mooney et al disclose that the device can be modified comprising coating a polymeric composition with PEI, and subsequently adsorbing an antigen to the coated polymeric composition, making a PEI-surface-modified device (see [0016]). Mooney teaches that PEI triggers an influx of antigen presenting cells (APCs) to the site of immunization and associates with antigen to form nanoparticles that are efficiently taken up by APCs (see [0118]).
With respect to instant claims 11 and 13, Mooney et al disclose that the scaffolds comprise PLG, alginate, or any other polymer known in the art (see [0041]). Mooney et al disclose of the scaffolds comprise nanoparticles comprising PLGA (see [0036], [0054], and [0069]).
With respect to instant claim 14, Mooney et al disclose of immunostimulatory compounds comprising a TLR agonist wherein said agonist further comprises heparin sulfate or a fragment thereof (see [0043]). While Mooney et al does not explicitly recite heparin, it is known in the art that heparin sulfate contains all of the structural variations found in heparin as evidenced by Shriver et al (see pg. 3).
With respect to instant claim 16, Mooney et al disclose cryogel formation with free-radical cross-linking alginate (see [0082]).
With respect to instant claims 30-33 and 36-37, Mooney et al disclose of immunostimulatory compounds being a TGF-beta inhibitor comprising LY2157299 (see [0051] and [0061]). Additionally, Mooney et al disclose of other small molecule immunomodulatory compounds that are generally hydrophobic (see [0148]).
As such, the teachings of Mooney et al anticipate the instant claims.
Applicant’s Arguments
Applicant respectfully traverses the 102 rejections (see pages 18 and 19 of the Remarks filed on 02/06/2026). As amended, the claimed microparticles or nanoparticles comprise a compound that blocks induction of Tregs; such component is not present in the compositions of Cheung. Additionally, Applicant asserts that the claimed microparticles or nanoparticles were amended to comprise a coating of APC membranes; such component is not present in the compositions of Mooney.
Response to Arguments
Applicant's arguments filed 02/06/2026 have been fully considered but they are not persuasive. Examiner acknowledges the amendments to the claims and has amended the rejections to address the new limitations. In regard to the teachings of Cheung, the art discloses that no expansion of CD4+ FoxP3+ regulatory T cells was observed with either Dynabeads or APC-ms (see page 4). Additionally, Mooney discloses that their device can be modified comprising coating a polymeric composition with PEI, and subsequently adsorbing an antigen to the coated polymeric composition, making a PEI-surface-modified device (see [0016]) and that PEI triggers an influx of antigen presenting cells (APCs) to the site of immunization and associates with antigen to form nanoparticles that are efficiently taken up by APCs (see [0118]). As such, the art meets the limitations of the amended claims and the 102 rejections are maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANAYA L MIDDLETON whose telephone number is (571)270-5479. The examiner can normally be reached M-F 9:30AM - 6PM with flex.
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, Vanessa Ford can be reached at (571) 272-0857. 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.
/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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