DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 22, 2025 has been entered.
3. Applicant requests rejoinder upon allowance of the examined claims, see Remarks/ Arguments submitted September 22, 2025, page 5, Request for rejoinder. At this point in prosecution there is no allowable subject matter, hence no rejoinder of distinct Groups set forth in the Election/ Restriction mailed September 29, 2024, page 3, segment 4.
4. Claims 1, 2, 4, 8, 10, 13, 14, 25, 31-33, 37, 41 and 46 are pending.
Claims 1, 2, 4, 8, 10, 13, 14 and 25, drawn to non-elected inventions are withdrawn from examination.
Claims 44, 45 and 47 have been cancelled.
Claims 1, 31, 32 and 41 have been amended.
Claims 31-33, 37, 41 and 46 are examined on the merits, species (cancer), melanoma.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
5. 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.
6. The rejection of claims 31-33, 37, 41 and 46 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 is maintained. Claims 44, 45 and 47 have been cancelled.
Applicant asserts “[a]s amended herein, the claims are directed to a composition that comprises effector cells that are armed with polyclonal anti-neoantigen antibodies that specifically bind to two or more neoantigens in a tumor of a subject. As discussed previously, the neoantigens are unique biological markers that are specific for a tumor in an individual having cancer. The claimed compositions represent targeted therapy, wherein the targets are unique for each cancer patient, and the pharmaceutical composition comprises polyclonal antibodies that recognize a plurality of the unique targets on the cell surface or secreted from tumor cells in the specific patient to whom the composition will be administered.”, see Remarks/ Arguments submitted September 22, 2025, page 6, 2nd paragraph (para.).
Applicant asserted in previous Remarks submitted (April 2, 2025) and herein, “[t]he present invention represents a personalized medical approach to treatment of cancer. The targets in each patient’s tumor cells are unique to that patient, and the claimed compositions contain binding agents that are specific for binding to a plurality of these targets in a particular patient.”, see Remarks/ Arguments, page 6, 3rd para.
Applicant further argues “[t]he binding agents are polyclonal antibodies that specifically bind to neoantigens associated with the tumor, i.e., a heterogeneous population of antibodies that specifically bind to the neoantigens. The structure of the anti-neoantigen antibodies is not important, so long as the functional characteristic, i.e., specific binding to a neoantigen, is provided. It is not possible to provide the structures of each antibody in a polyserum that is produced in response to a neoantigen peptide. However, the functional characteristics of the polyclonal anti-neoantigen antibodies are described in the specification, i.e., specific binding to neoantigen proteins that comprise tumor-specific mutations in extracellular domains of membrane proteins and/or secreted proteins in the tumor. Polyclonal antibodies that specifically bind to neoantigens as claimed are exemplified in working examples in the specification, thus providing written description support for the claimed invention. (See Examples 1 and 2.)”, see Remarks/ Arguments, page 6, 3rd para.
Applicant’s arguments and points of view have been carefully considered, but fail to persuade.
Foremost, the claims previously read on the claimed composition comprising anti-neoantigen antibodies including polyclonal antibodies, see Amendments to the Claims submitted April 2, 2025, original claim 31, claim 45 (now cancelled) and original claim 46.
And as stated in the Final Action mailed May 20, 2025, page 6, 2nd para., [t]here continues to be a host of antibodies that have not been identified or characterized by both, structure and function. Applicant describes the functional attribute, but does not describe the structure-identifying information about the polyclonal anti-neoantigen antibodies essential to the claimed composition. Applicant does not describe a representative number of species falling within the scope of the genus or structural common feature(s) to the members of the genus so one of skill in the art can visualize or recognize the members of the genus of the actual polyclonal anti-neoantigen antibodies themselves. Accordingly, the specification does not adequately describe a representative number of members of the genus or provide a written description of the genus comprising a host of polyclonal antibodies that bind two or more neoantigens.
Given the heterogeneity of polyclonal antibodies it is art known these binding agents will recognize multiple epitopes and tend to have lower binding affinity, thereby not able to bind targets with high specificity. Hence, what is claimed is a multitude of binding agents with know known structure
Applicant has not pointed to any evidence within the disclosure that describes the antibodies as required by the test set forth in Ariad. This means that like any other product, an antibody invention should be claimed by an antibody structure, at least a core structure of a claimed genus of antibodies coupled with a function associated with the core structure, not antigen core structure.
The specification does not make clear Applicant are in possession of all the possible binding molecules that are undefined and uncharacterized falling within the potentially large genus to establish possession. No corollary nexus has been established between structure and function. There is insufficient to support the generic claims.
As noted in the rejection herein, the USPTO released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the polyclonal anti-neoantigen antibodies essential to the claimed invention to demonstrate possession that fulfill the requirements of a structure- function relationships of written description. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
“When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the Applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
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), the following is noted.
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).
The instant disclosure, including the claims fails to disclose a representative number of species falling with the scope of the genus and/or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of polyclonal anti-neoantigen antibodies.
Here, Applicant’s claims include antibodies that encompass various structural, specificities and functional attributes to fulfill the requirements of a structure-function relationship of written description, but do not describe the structure-identifying information about the polyclonal anti-neoantigen antibodies, nor describe a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the polyclonal anti-neoantigen antibodies.
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that exhibit this functional property.
The specification does not evidence the possession of all binding molecules that are undefined and uncharacterized falling within the potentially large genus to establish possession.
Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 U5PQ2d 1398.
The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
Given the highly diverse nature of antibodies, one skilled in the art cannot envision the structure of the said antibodies by simply knowing where its binds. Abbvie establishes “[o]ne needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.” Id.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. For the reasons of record and cited herein the rejection is maintained.
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 claims are drawn to a composition comprising effector cells armed with polyclonal anti-neoantigen antibodies that bind two or more neoantigens in a subject’s tumor, an immune checkpoint inhibitor and a pharmaceutically acceptable carrier.
The written description in this instant case does not set forth a plethora of compositions comprising a host of effector cells armed or coated with a host of polyclonal anti-neoantigen antibodies.
The written description is not commensurate in scope with the plethora of polyclonal anti-neoantigen antibodies contained within the composition. The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of the polyclonal anti-neoantigen antibodies. There seems to be no identifying sequence numbers, nor six complementarity-determining regions (CDRs) that would evidence Applicant’s written descriptive support for the genus of polyclonal anti-neoantigens antibodies encompassed by the claims.
The ability to make the polyclonal anti-neoantigen antibodies essential to the claimed product does not place the skilled artisan in possession of the relevant identifying characteristics of a genus of said antibodies commensurate in scope with the claimed invention.
The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of the components within the composition, in particular the polyclonal anti-neoantigen antibodies that places the skilled artisan in possession of the genera of the components in scope with the claimed invention.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 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.
“A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-1569.
Vas-Cath Inc. V Mahurkar, 19 U5PQ2d 1111, clearly states 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).
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 115).
The skilled artisan cannot envision the detailed structure of the broad class of anti-neoantigen antibodies that are remiss of sequences, therefore conception is not achieved until reduction to practice has occurred, 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 a reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 U5PQ 2d 1601 at 1606 (CAFC1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts. 18 U5PQ2d 1016.
Furthermore, In The Reagents of the University of California v. Eli Lilly (43 U5PQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of DNA molecules, usually defined by a nucleotide sequence, falling within the scope of the claimed genus. At section B(l), the court states that "An adequate written description of a DNA...'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".
At the time the application was filed Applicant does not seem to be in possession of a composition comprising effector cells armed or coated with a host of polyclonal anti-neoantigen antibodies. Applicant did not have possession of the breadth of these molecules contained within the claimed composition.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of polyclonal anti-neoantigen antibodies directed to different neoantigens, wherein each comprises a single amino acid substitution essential to the claimed invention to demonstrate possession that fulfill the requirements of a structure-function relationships of written description. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
The instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genera and/or structural common to the members of the genera so the one of skill in the art can visualize or recognize the members of the genus of polyclonal anti-neoantigen antibodies.
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).
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that exhibit this functional property, i.e., bind different entities.
The specification does not evidence the possession of all the multitude of anti-neoantigen antibodies that are undefined and uncharacterized falling within the potentially large genus to establish possession. Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 U5PQ2d 1398.
The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
7. The rejection of claims 31-33, 37, 41 and 46 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition comprising effector cells armed with polyclonal anti-neoantigen antibodies, wherein the antibodies specifically bind to two or more neoantigens in a melanoma tumor and a PD-1 monoclonal antibody checkpoint inhibitor with a pharmaceutically acceptable carrier, does not reasonably provide enablement for a composition comprising effector cells armed with anti-neoantigen antibodies and a pharmaceutically acceptable carrier, wherein the anti-neoantigen antibodies specifically bind to two or more neoantigens in any and all cancers and an immune checkpoint inhibitor is maintained. Claims 44, 45 and 47 have been cancelled.
Applicant asserts, “[a]s amended herein, the claims are directed to a composition that comprises effector cells that are armed with polyclonal anti-neoantigen antibodies that specifically bind to two or more
neoantigens in a tumor of a subject. Selection of neoantigen targets in a tumor, production of high-affinity polyclonal antibodies that specifically bind to the neoantigen targets, and arming of effector cells with the anti-neoantigen polyclonal antibodies are described in the working examples of the specification as filed. The process of selecting neoantigen targets, producing polyclonal antibodies, and arming effector cells will be the same regardless of the tumor to be treated. Thus, the working examples and the disclosure of the specification provide guidance to enable the skilled artisan to make and use the claimed invention without undue experimentation.”, see Remarks/ Arguments submitted September 22, 2025, page 7.
Applicant’s arguments have been carefully considered, but fail to persuade.
The working examples set forth in the specification exemplify the production of polyclonal antibodies with nine selected mutated epitopes of B16-F10 melanoma tumor proteins, see Example 1 beginning on page 59; and Example 2 beginning on page 66. Within these Examples, specific mutated epitopes with KLH conjugates are given to rabbits in the production of polyclonal antibodies. The claims read broadly on polyclonal anti-neoantigen antibodies that bind neoantigens in any tumor. Hence, the rejection is maintained for the reasons of record.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Applicant’s claimed invention reads on a composition comprising effector cells armed with polyclonal anti-neoantigen antibodies and a pharmaceutically acceptable carrier, wherein molecules the polyclonal anti-neoantigen antibodies specifically bind to two or more neoantigens in a tumor and wherein the neoantigens comprise tumor-specific mutations further comprising an immune checkpoint inhibitor, including PD-1, PD-L1 and CTLA-4 inhibitors presented in the claims.
The state of the art cites “for high-mutational-burden tumors (e.g., melanoma, lung adenocarcinoma, and bladder carcinoma), algorithms should be used to narrow down the number of candidate neoepitopes, followed by experimental validation with emphasis on peptides of clonal origin. For cancers with low mutational burden (e.g., glioblastoma and acute myeloid leukemia), all predicted neoepitopes should be experimentally validated.”, see page 816, 2nd column of Vitiello et al. (Nature Biotechnology 35(9): 815-801, September 2017). As further of record in Vitiello, “[t]he majority of tumors are highly heterogeneous, and distinct regions of a single lesion can have different mutational profiles.”, see page 816, 1st column, last full paragraph. Hence, neoantigens of varying degrees of mutation and expression may or may not be expressed by any and all cancers, therefore the polyclonal anti-neoantigen antibodies will range in specificity and clinical benefit.
Applicant’s specification supports the administration of effector cells armed with four high tumor-binding or nine antibody cocktail and PD1i, see Figure 8, Figure 10, Figure 12, Figure 14 and corresponding figure captions on pages 10 and 11. Tables 1-3 set forth selected mutated peptides and rabbit polyclonal antibodies, which have affinity for these said peptide targets, see pages 59-67. However, the specification does not evidence the utility of the broadly claimed composition including a host of effectors cells armed with polyclonal anti-neoantigen antibodies specific for a host of cancers.
Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claim broadly reading on a composition comprising effector cells armed with polyclonal anti-neoantigen antibodies specific for any and all types of cancers including carcinoma, sarcoma, lymphoma and leukemia. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, a composition comprising effector cells coated with a variety of anti-neoantigens antibodies with an immune checkpoint inhibitor are not sufficient to implement in the intended use of cancer treatment. The experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Conclusion
8. All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
9. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached between 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
December 5, 2025
/Alana Harris Dent/Primary Examiner, Art Unit 1643