DETAILED ACTION
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 .
Status of Application, Amendments and/or Claims
The amendment of 18 May 2026 has been entered in full. Claims 1, 5, and 6 are amended. Claims 2, 4, 7, 9, and 11-15 are cancelled.
It is noted to Applicant that the claim status identifier for claim 5 still indicates that the claim is “original”. However, the Examiner acknowledges that claim 5 has clearly been amended and that this amended version will be under consideration.
Claims 6, 8, and 10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06 January 2026.
Claims 1, 3, and 5 are under consideration in the instant application.
Drawings
The replacement drawings were received on 18 May 2026. These drawings are acceptable.
Withdrawn Objections and/or Rejections
1. The objection to the drawings as set forth at page 3 of the previous Office Action of 18 February 2026 is withdrawn in view of the submission of replacement drawings (18 May 2026).
2. The objection to claim 1 as set forth at page 3 of the previous Office Action of 18 February 2026 is withdrawn in view of the amended claim (18 May 2026).
3. The objection to the specification as set forth at pages 3-4 of the previous Office Action of 18 February 2026 is withdrawn in view of the amended specification (18 May 2026).
4. The rejection of claims 2 and 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph as set forth at pages 7-8 of the previous Office Action of 18 February 2026 is withdrawn in view of the cancelled claims (18 May 2026).
5. The rejection of claim 5 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph as set forth at pages 8-9 of the previous Office Action of 18 February 2026 is withdrawn in view of the amended claim (18 May 2026).
6. The rejection of claims 1, 3, and 5 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (written description) as set forth at pages 9-14 of the previous Office Action of 18 February 2026 is withdrawn in view of amended claim 1 (18 May 2026).
7. The rejection of claims 1, 3, and 5 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (scope of enablement) as set forth at pages 15-21 of the previous Office Action of 18 February 2026 is withdrawn in view of amended claim 1 (18 May 2026).
8. The rejection of claims 1 and 2 under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Colonna et al. (U.S. Patent 11,066,456), as evidenced by Genbank Accession No. NM_00127078, Schmid et al. (“Schmid1”, J Neurochem 83: 1309-1320, 2022), and Schmid et al. (“Schmid2”, Genbank Accession No. AAO06114.1) as set forth at pages 23-24 of the previous Office Action of 18 February 2026 is withdrawn in view of amended claim 1 (18 May 2026). Specifically, Colonna et al., Schmid1, and Schmid2 do not teach a pharmaceutical composition comprising a TREM2 protein fragment consisting of or comprising the amino acid sequences of SEQ ID NOs: 4 and 5.
New 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.
9. Claims 1, 3, and 5 are 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.
9a. Claims 1, 3, and 5 are rejected as being indefinite because it is not clear how the TREM2 fragment of claim 1 can "consist" of amino acids "having" a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5. Claim 1 recites both open (“having”) and closed (“consisting of”) terminology and thus, it is not clear whether open or closed language is intended for the identity of the fragment. See MPEP § 2111.03. In other words, does the TREM2 fragment consist of or comprise the amino acid sequence of SEQ ID NO: 4 or 5?
Please note that this issue could be overcome by amending claim 1 to recite, for example, “…protein fragment consisting of the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5” or “…protein fragment comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5”.
Maintained Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
10. Claims 1, 3, and 5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., law of nature or natural phenomenon) without significantly more. The basis for this rejection is set forth in detail for claims 1-5 at pages 4-7 of the previous Office Action of 18 February 2026.
Claim 1 recites a pharmaceutical composition for treating or ameliorating heart failure, wherein the pharmaceutical composition comprises a TREM2 (triggering receptor expressed on myeloid cells 2) protein fragment consisting of amino acids having a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5.
The instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
(i) At page 6 of the Response of 18 May 2026, Applicant argues that protein fragments of TREM2 consisting of amino acids having a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5 are soluble, and capable of being injected (paragraph starting at page 3, line 19 and paragraph starting at page 10, line 21). Applicant also submits that protein fragments of TREM2 consisting of amino acids having a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5 upon injection can promote the functional and structural improvement of the heart by remodeling the infarcted heart, and thus is effective in the treatment of heart failure, such as heart failure after myocardial infarction (paragraph starting at page 11, line 27). Applicant asserts that this is in contrast to the naturally occurring, longer TREM2 protein, that is a cell membrane protein that contains a transmembrane domain (paragraph at page 2, line 18 and paragraph at page 5, line 13). Applicant contends that the claimed protein fragments have a structural difference was well as a property not found in a naturally occurring TREM2 protein.
Applicant’s arguments have been fully considered but are not found to be persuasive.
(i) First, it is noted that the instant claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as discussed directly above, because it is not clear whether open or closed language is intended for the claimed TREM2 fragment. Therefore, one interpretation of claim 1 is “open” claim language, wherein the TREM2 is a protein having/comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5. Sleeman et al. teach a naturally-occurring polypeptide expressed in lymph node stromal cells of fsn -/- mice, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 50 (column 3, lines 14-25). The amino acid sequence of SEQ ID NO: 50 of Sleeman et al. comprises amino acids that are 100% identical to the instant TREM2 amino acid sequences of SED ID NO: 4 and 5 (see amino acids 1-158 and amino acids 19-171, respectively, of SEQ ID NO: 50 of Sleeman et al.).
(ii) Furthermore, regarding the alternative “closed” claim language interpretation of claim 1 wherein the pharmaceutical composition comprises a TREM2 protein fragment consisting of the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5, these peptide fragments are made up of fragments of the naturally occurring murine TREM2 protein. In Association for Molecular Pathology v. Myriad Genetics, 569 U.S. __, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), the Supreme Court held that “Myriad did not create anything. To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” Id. at 2117. “Myriad found the location of the BRCA1 and BRCA2 genes, but that discovery, by itself, does not render the BRCA genes ‘new . . . composition[s] of matter,’ § 101, that are patent eligible.” Id. “Nor are Myriad’s claims saved by the fact that isolating DNA from the human genome severs chemical bonds and thereby creates a nonnaturally occurring molecule.” Id. at 2118. The same analysis applies to the instant claims. Claim 1 is directed to a fragment of a naturally occurring murine TREM2 protein, separated from the rest of the protein. Applicant has identified certain peptides, with naturally occurring amino acid sequences, that have the property of promoting the functional and structural improvement of the heart by remodeling the infarcted heart, but that does not render the peptides new compositions of matter that are patent eligible. Rather, claims 1, 3, and 5 are directed to a product of nature. Based upon the limited disclosure in the specification, there is no indication that a peptide fragment consisting of the amino acid sequence of SEQ ID NO: 4 or 5 of the claims has any characteristics (structural, functional, or otherwise) that are different from naturally occurring murine TREM2. Relevant literature teaches that full-length naturally occurring TREM2 has a cardioprotective role. For example, Smart et al. (Cardiovascul Res 119: 2312-2328, 2023) teach that the loss of TREM2 (using mice with a genetic deletion of TREM2) leads to exacerbated cardiac hypertrophy, diastolic function, renal dysfunction and decreased capillary density, as well as the loss of pro-angiogenic transcriptional programs and increased proinflammatory cytokine production in macrophages (page 2314, column 1, 3rd full paragraph; abstract). Fu et al. also disclose that mouse cardiomyocytes express low levels of TREM2 and that overexpression of TREM2 reduces infarct size and improves cardiomyocyte survival after acute myocardial infarction in a mouse model (page 34, top of column 1; abstract).
(iii) Lastly, although Applicant argues that the claimed TREM2 peptide fragments are capable of being injected, there is no indication that simply having the capability of being injected changes the structure, function, or other properties of TREM2. For instance, if full-length murine TREM2 is expressed on the surface of a naturally-occurring cell, such cell can be isolated and injected. The structure, function, or other properties of TREM2 remain unchanged.
(iv) In conclusion, the claims do not recite any additional elements that integrate the judicial exception into a practical application. There is no difference in function and no difference in structure (i.e., there are no structural changes to TREM2 protein). There is no evidence that peptide fragments consisting of the amino acid sequences of SEQ ID NO: 4 or 5 have any activity different from full-length TREM2 present on a cell surface. As there are no different characteristics between the claimed nature-based product and its natural counterpart, the claimed composition does not have any markedly different characteristics and the claims as a whole do not amount to significantly more than the "product of nature" by itself (step 2B: No). Therefore, the instant claims do not qualify as eligible subject matter under 35 U.S.C. §101.
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.
11. Claims 1, 3, and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sleeman et al. (U.S. Patent 6,797,271; issued 28 September 2004). The basis for this rejection is set forth for claims 1 and 3-5 at pages 21-22 of the previous Office Action of 18 February 2026.
Sleeman et al. teach a polypeptide and/or a portion of a polypeptide expressed in lymph node stromal cells of fsn -/- mice, wherein the polypeptide portion comprises the amino acid sequence of SEQ ID NO: 50 (column 3, lines 14-25). It is noted that the amino acid sequence of SEQ ID NO: 50 of Sleeman et al. comprises amino acids that are 100% identical to the instant TREM2 amino acid sequences of SED ID NO: 4 and 5 (see amino acids 1-158 and amino acids 19-171, respectively, of SEQ ID NO: 50 of Sleeman et al.). Sleeman et al. disclose that the polypeptide may be administered to treat cardiac failure (column 3, lines 49-63). Sleeman et al. also state that the polypeptide is present within a pharmaceutical composition, meeting the limitations of instant claim 1 (column 12, lines 1-13, 39-65). Sleeman et al. teach that the pharmaceutical composition may be injected (column 12, lines 39-44).
(i) At the bottom of page 7 of the Response of 18 May 2026, Applicant states that current independent claim 1 recites “A pharmaceutical composition for treating or ameliorating heart failure, wherein the pharmaceutical composition comprises a TREM2 (triggering receptor expressed on myeloid cells 2) protein fragment consisting of amino acids having a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5”. Applicant argues that SEQ ID NO: 4 discloses an amino acid sequence having a length of 158 amino acids while SEQ ID NO: 5 discloses an amino acid sequence of 153 amino acids. Applicant asserts that in contrast, Sleeman does not teach a TREM2 protein fragment consisting of amino acids having a sequence identical to SEQ ID NO: 4 or SEQ ID NO: 5.
Applicant’s arguments have been fully considered but are not found to be persuasive. It is noted that the instant claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as discussed directly above, because it is not clear whether open or closed language is intended for the claimed TREM2 fragment. Therefore, one interpretation of claim 1 is “open” claim language, wherein the TREM2 is a protein comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5.
The amino acid sequence of SEQ ID NO: 50 of Sleeman et al. is a protein that is 227 amino acids in length and that comprises amino acids that are 100% identical to the instant TREM2 amino acid sequences of SED ID NO: 4 and 5 (see amino acids 1-158 and amino acids 19-171, respectively, of SEQ ID NO: 50 of Sleeman et al.). Thus, Sleeman et al. still anticipate instant claims 1, 3, and 5.
Conclusion
No claims are allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Daws et al. (Eur J Immunol 31: 783-791, 2001) teach a naturally-occurring murine TREM2b protein that comprises the instant amino acid sequences of SEQ ID NOs: 4 and 5 (see page 7685, Figure 2; page 787, column 2, Discussion)
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 BRIDGET E BUNNER whose telephone number is (571)272-0881. The examiner can normally be reached Monday-Friday 9:00 am-6:00 pm.
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BEB
Art Unit 1647
29 June 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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