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 .
Status of Application, Amendments and/or Claims
2. Applicant’s response dated 7/22/2026 is considered and entered into record. Claims 1-31 are currently pending.
Election/Restriction
3. Applicant’s election without traverse of Group I, claims 1-13; Aptamer as inventive group ‘B’; and species - Alzheimer’s disease (AD) as the neuroinflammatory/neurodegenerative disease; amino acid residues 14-174 of SEQ ID NO: 1 as the extracellular domain of TREM2; and SEQ ID NO: 7 as the stalk region of TREM2, and SEQ ID NO: 12 as the aptamer, in the reply filed on 22 July 2026 are acknowledged.
4. Upon further consideration and relevant search of the aptamers, non-elected SEQ ID NO: 13 will be rejoined with the elected SEQ ID NO: 12 aptamer species and examined in the instant Office Action.
5. The requirement is deemed proper and is therefore made FINAL.
6. Claims 14-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 22 July 2026.
7. Claims 1-13, drawn to a molecule that specifically binds to human TREM2 protein, and a pharmaceutical composition comprising the same, are under examination in the instant application.
Specification
8. The disclosure is objected to because of the following informalities:
Internet address:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see para 00110 on pages 32 and 33, for example). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate action is required.
Claim Objection
9. Claims 1, 3-6 and 8-9 are objected to because of the following informalities:
10. Regarding claims 1, 3-6 and 8-9, acronym “TREM2”, recited should be spelled out for clarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Written description
11. 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.
12. 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.
13. Claims 1-11 and 13 are rejected under 35 U.S.C. 112(a), 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(s), at the time the application was filed, had possession of the invention.
14. The claims are drawn to a molecule that specifically binds to the extracellular domain of human TREM2 protein, stabilizes the protein and/or reduces shedding of the ectodomain of the protein, wherein the molecule is not an antibody or an antigen binding fragment thereof (claims 1, 3, 8); wherein: the molecule is an aptamer (claim 2); the aptamer is an oligonucleotide or a peptide aptamer (claim 10), and a slow off-rated modified aptamer (SOMAmer) (claim 11); and the molecule stabilizes the TREM2 protein on the surface of cells (recited in claim 7, 9) expressing TREM2. The claims also recite that the molecule binds to the stalk region comprising SEQ ID NO: 7 of human TREM2 protein (claims 5, 6); and the extracellular domain of human TREM2 comprises amino acids 14 to 174 of SEQ ID NO: 1 (claim 4). Claim 13 recites a pharmaceutical composition comprising the molecule and a pharmaceutically acceptable carrier.
15. The specification of the instant application teaches that TREM (TREM1 and TREM2) or triggering receptors expressed on myeloid cells, are a group of transmembrane glycoproteins (para 004), wherein human TREM2 belongs to the immunoglobulin super family (IgSF), includes a signal peptide, a single V-type immunoglobulin domain, a stalk region, a transmembrane domain and a cytoplasmic tail (para 0020), and is expressed on macrophages, dendritic cells, osteoclasts, microglia, lung epithelial cells and hepatocarcinoma cells, but not on myeloid cells in the blood (para 005). The specification also teaches that the extracellular domain of human TREM2 comprises amino acids 14-174 of SEQ ID NO: 1, and the ectodomain of TREM2 is the released portion of the extracellular domain after sheddase cleavage during proteolytic processing (para 0021, 0022, 0080). The specification further teaches that molecules that specifically bind to the extracellular domain of TREM2 protein, inhibit the shedding of TREM2 ectodomain, stabilize the protein on cell surface, and maintain or increase TREM2 functions like its binding to cognate ligands, intracellular signaling, increasing phagocytosis, etc. , wherein such molecules include those which are not antibodies, such as small molecular weight compounds, modified oligonucleotides, macrocyclic molecules and oligonucleotide/peptide aptamers (para 007, 0076, 0219). Example 1 teaches stabilization of cell surface TREM2 by custom made SOMAmers, specifically SOMAmers UX95-90BC and KX86-94WC having SEQ ID NOs: 12 and 13 respectively, which can bind to the human TREM2 extracellular domain, stabilize and increase the cell surface human TREM-2 on CHO-hTREM2 cells, while control SOMAmer EX83-95HC does not bind to cell surface human TREM2 (Figures 4, 5A, B; Table 1). However, other than aptamer/SOMAmers having SEQ ID NOs: 12, 13 (as molecule species which is not an antibody or an antigen binding fragment thereof), the specification does not teach functional or structural characteristics of a (i) molecule (as recited in claims 1, 3-9, 13) or an (ii) aptamer (claims 2, 10, 11) included in the broad genus of a molecule, that specifically binds to the extracellular domain of the TREM2 protein, stabilizes the protein, and reduces shedding of the ectodomain. There is no adequate written description for all (non-antibody) molecules or all aptamers, as recited in the instant claims.
16. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. However, in this case, the specification has not shown a relationship between the structure, function, or properties of the claimed genus of molecules or aptamers. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
17. The specification further adds that aptamers and SOMAmers that specifically bind to a target molecule like the stalk region of human TREM2 protein, can be generated and selected in vitro using the SELEX process as described in the art and prior patents (para 00220-00221), i.e. aptamers or SOMAmers can be obtained by conventional methods known in the art. The situation is analogous to the decision in the University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004), wherein the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face. Since the specification does not disclose to the public the structures claimed, it does not meet the written description requirement of 35 USC § 112(a), first paragraph.
18. Applicant has claimed a broad genus of molecules or aptamers that: (a) specifically bind to the extracellular domain of the TREM2 protein, (b) stabilize the protein, and (c) reduce shedding of the ectodomain. The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). The court has further stated that “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.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002).
19. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 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).
20. With the exception of 2 SOMAmers comprising SEQ ID NOs: 12 and 13 (Example 1) that specifically bind to the extracellular domain of the TREM2 protein and stabilize the protein levels, the skilled artisan cannot envision the detailed chemical structure of the genus of encompassed molecules/aptamer molecules, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation or production. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
21. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class.
22. Therefore, the claims do not meet the written description provision of 35 U.S.C. §112, first paragraph. 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).
Claim Rejection - 35 USC § 103
23. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
24. Claims 1-11 and 13 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Colonna et al (US PGPB 20090081199, 3/26/2009), in view of Brudno et al (Nat Chem Biol 6: 148-155 (1-23), 2010), and Zichi et al (US 7,964,356; 6/21/2011), as evidenced by PNA (Peptide nucleic acid - Wikipedia downloaded on 9/22/2026, pages 1-6), and Zhong et al (PLOS ONE 19: 1-21, 2024).
25. Colonna et al teach novel activating receptors of the Ig-superfamily (TREM2) that are expressed on different cells including dendritic cells (abstract; para 0364). The reference teaches a human TREM-2 sequence of SEQ ID NO: 4 comprising the sequence of SEQ ID NO: 18 (Fig 1B; para 0103, 0109), which has an extracellular domain encompassing amino acids 14 to 167 (para 0106), wherein the TREM2 sequence is identical to instant amino acid sequence of SEQ ID NO: 1 (residues 14 to 174) (see attached Appendix a, b, showing SEQ ID NO: 18 of TREM2 having 100% match with instantly recited SEQ ID NO: 1). As stated in the instant specification (para 0023), the sequence identical to instantly recited stalk region (SEQ ID NO: 7) is a (62 amino acid) portion of the TREM2 extracellular domain (SEQ ID NO: 18) of Colonna et al (Appendix c) (instant claims 4, 6). Colonna et al teach agents (molecules) modulating the activity of the polypeptide of the invention (TREM2), wherein the molecule includes nucleic acid, small molecule, etc. (para 0215, 0280). The reference also teaches pharmaceutical compositions comprising the nucleic acid molecules and a pharmaceutically acceptable carrier (para 0200, 0218). Colonna et al further teach peptide nucleic acids or PNAs that can be used like antisense molecules for therapeutic applications, wherein antisense molecules can specifically bind to receptors expressed on cell surface (i.e. extracellular) (para 0132, 0133, 0128). (instant claims 1, 3-9, 13). Even though the reference does not teach that the nucleic acid or PNA molecule "stabilizes" cell surface TREM2, or "reduces shedding of the ectodomain" (instant claims 8, 9), this will result once the PNAs specifically binds to the extracellular domain of human TREM2 as stated in para 00269 on page 79 of the instant specification.
26. Colonna et al do not teach aptamer.
27. Brudno et al teach systems for PNAs and refers to PNAs as PNA aptamers that can complement other molecules like nucleic acid aptamers "by offering improved cellular or chemical stability, lower immunogenicity, improved cell penetration, or resistance to degradation" (page 2, para 3), wherein PNAs have protein binding properties, including receptor targets, and can be useful therapeutic agents for regulating protein expression, as evidenced by Zhong et al (Abstract; page 2, para 2; Conclusion and discussion, para 1). That PNAs are aptamers is also evidenced in PNA (PNA Peptide nucleic acid - Wikipedia downloaded on 9/22/2026, pages 1-6) which teaches that PNAs can fold into three-dimensional structures like aptamers (page 2, para 2). It is noted that para 0044 of the instant specification defines "aptamer" as a "polynucleotide or polypeptide molecule that, through its ability to adopt a specific three-dimensional conformation, binds to a protein target and modifies the protein target or the functional activity or stability of the protein target" (instant claims 2, 10).
28. Colonna et al or Brudno et al do not teach SOMAmer.
29. Zichi et al teach aptamers having slower dissociation rate constants using modified and improved SELEX methods, wherein the aptamers react with specific target molecules (or specifically bind to a target molecule) (Abstract; col 1, para 2; Background, para 2, 3). The reference teaches producing aptamers by a slow off-rate enrichment process, which results in “nucleic-acid target complexes with fast dissociation rates” to “dissociate and not reform, while complexes with slow dissociation rates” to stay intact” (col 4, para 1), wherein a SELEX target can be a receptor (col 13, lines 43, 45). Even though Zichi et al do not teach the term “SOMAmer”, the reference teaches using improved SELEX method for producing aptamers using a slow off-rate enrichment process, which is not only comparable to the teaching in para 00221 of the instant specification, but also incorporated by reference in the instant disclosure. The reference therefore, implicitly teaches “SOMAmers” (instant claim 11).
30. It would therefore have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art, to have modifed a peptide nucleic acid or aptamer molecule that specifically binds to cell surface receptors (like human TREM2) based upon the combined teachings of Colonna et al and Brudno et al, by considering SOMAmer aptamers in view of the teaching of Zichi et al. The person of ordinary skill would have been motivated to use SOMAmers as these aptamer molecules are produced by a slow off-rate enrichment process, resulting in “nucleic-acid target complexes with fast dissociation rates” to “dissociate and not reform, while complexes with slow dissociation rates” to stay intact” (Zichi et al), i.e. said aptamers “will bind to the target for a longer duration”, thereby aiding in diagnostic and therapeutic applications (Zichi et al, col 25, para 3). The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references at the time of filing of the instant invention.
31. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
Claim Objection
32. Claim 12 is objected to as being dependent upon a rejected base claim/s, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
33. No claims are allowed.
34. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aditi Dutt whose telephone number is (571)272-9037. The examiner can normally be reached on M-F 9:00am-5:00pm.
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/A. D./
Examiner, Art Unit 1675
/KIMBERLY BALLARD/
Primary Examiner, Art Unit 1675
Prosecution Insights