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 .
DETAILED ACTION
Election/Restriction
2. Applicant’s election without traverse of Group I, claims 1, 5-6, 10, 14, 49 and 53-55, in the reply filed on 01 October 2025 is acknowledged. Applicant’s election of an IgG1 heavy chain constant region having the combination of substitutions: L234A, L235E and G237A as the species of IgG1 heavy chain constant region is also acknowledged. Claims 50-52 and 56-59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01 October 2025.
3. The restriction requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, and/or Claims
4. The Response filed on 01 October 2025 has been entered in full. Claims 50-53 and 56-59 have been withdrawn as discussed supra. Therefore, claims 1, 5-6, 10, 14 and 49-59 are pending, and claims 1, 5-6, 10, 14, 49 and 53-55 are the subject of this Office Action.
Specification
5. The disclosure is objected to because of the following informalities: An updated status of the parent nonprovisional application should be included in the first sentence of the specification. A statement reading “… 17/472.051, filed September 10, 2021, now U.S. Patent No. 11,952,420 …”, should be entered. Appropriate correction is suggested.
6. Applicant’s attempt to amend the specification (filed 29 March 2024) to provide a new incorporation statement is noted but not compliant. Such amendment cannot be accepted, as the only means for correcting this deficiency is submitting a substitute specification. (See Official Gazette, Notices 08 November 2005, available at https://www.uspto.gov/web/offices/com/sol/og/2005/week45/og200545.htm).
This requirement was reaffirmed in an Official Gazette issued by the Office on May 14, 2019. Specifically, the notification stated:
“A Substitute Specification is Required for Certain Amendments: Applicants are reminded that if a reply to a notice sent by OPAP necessitates changes to the specification (excluding the claims or abstract), then the notice will require applicant to submit an amendment in the form of a substitute specification in compliance with 37 CFR 1.121(b) (3) and 37 CFR 1.125. Such an amendment to the specification cannot be made by way of replacement paragraph or replacement section under 37 CFR 1.121 (b)(1) or (b)(2). The only format for an amendment to the specification useable for pre-grant publication purposes is a substitute specification. See MPEP Section 714.01(e).” (See Official Gazette, 1462 Off. Gaz. Pat. Office 121 (14 May 2019)).
Claim Rejections - 35 USC § 112 (Written Description)
7. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
8. Claims 1, 5-6, 10, 14, 49 and 53-55 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
9. The claims are drawn quite broadly to an isolated antibody which specifically binds to a triggering receptor expressed on myeloid cells-1 (TREM-1), comprising a heavy chain variable region (VH), a light chain variable region (VL), and an IgG1 heavy chain constant region, wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions and/or deletions compared to a wild-type IgG1 heavy chain constant region (SEQ ID NO: 9). The claims also recite wherein the antibody specifically binds to a TREM-1 epitope comprising amino acids D38 to L45, E46 to Q56, and/or Y90 to L96 of SEQ ID NO: 1; . The claims also recite wherein the antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, (i) wherein the heavy chain CDR3 comprises DMGIRRQFAY (SEQ ID NO: 26); (ii) wherein the heavy chain CDR2 comprises RIRTKSSNYATYYAASVKG (SEQ ID NO: 25); and/or (iii) wherein the heavy chain CDR1 comprises TYAMH (SEQ ID NO: 24). The claims also recite wherein the antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, (i) wherein the light chain CDR1 comprises RASQSVDTFDYSFLH (SEQ ID NO: 27), (ii) wherein the light chain CDR2 comprises RASNLES (SEQ ID NO: 28); and/or (iii) wherein the light chain CDR3 comprises QQSNQDPYT (SEQ ID NO: 29). Thus, the claims have been broadly interpreted by the Examiner as reading upon an extremely large genus of antibodies that are defined only by a partial structure and a desired function/activity.
10. The specification discloses one antibody that is defined by particular amino acid sequence for the heavy and light chain variable regions. This antibody, designated mAb 0318, is disclosed as binding the human TREM-1, and further discloses particular variants that have substitutions in the IgG1 heavy chain constant region that also bind human TREM-1 (See Figure 1), do not agonize TREM-1 signaling (Figure 3), less immunogenic (See Figure 8) and have a decreased binding affinity for FcγRs (See Figure 10) . However, the specification does not provide sufficient written description as to the structural features of the claimed genus of antibodies encompassed by the claims that have the same binding specificity and functional activity.
11. A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one 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."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
12. It is well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. Based on the instant disclosure, one skilled in the art would not know which residues in the CDRs are critical for binding. In the instant case, there is insufficient guidance based on the reliance of disclosure of 1 antibody, wherein the antibody comprises (1) a light chain variable region comprising the sequence SEQ ID NO:15 and a heavy chain variable region comprising the sequence SEQ ID NO: 14 to direct a person of skill in the art to select or to predict particular residues or CDRs as essential for the functional properties recited in the claims.
13. It is well established in the art that the amino acid sequences and conformations 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. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff, et al. (PNAS, 1982. Vol. 79, page 1979). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum, et al. (J. Mol. Biol., 262:732-745) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al. (Journal of Immunology, 2002. 169:3076-3084) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column).
14. The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset, et al. (Biochemical and Biophysical Research Communications, 2003. 307:198-205) which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset, et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left column). Chen, et al. (Journal of Molecular Biology, 1999. 293:865-881) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Wu, et al. (Journal of Molecular Biology, 1999. 294:151-162) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left column) but certain residues have been identified as important for maintaining conformation.
15. In the absence of sufficient direction and guidance, the disclosure of a limited number of species of antibodies does not provide sufficient written description for the entire genus of modified immunoglobulin molecules encompassed by the claims in view of the evidence cited supra.
16. For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species, cannot be achieved by disclosing only one or two species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
17. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of antibodies, and 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 reference to a potential method of isolating it. The compound 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.
18. One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, 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.
19. Therefore, only an antibody comprising: (1) a heavy chain variable region comprising the sequence 14 and a light chain variable region comprising the sequence SEQ ID NO: 15; or (2) a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 24-26, respectively, and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 27-29, respectively, but not the full breadth of the claims meets 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 Rejections - 35 USC § 102
20. 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 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.
21. 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.
22. Claim(s) 1, 5, 10, 14, 49 and 53-55 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Henriksen et al (WO 2016/009086-A1; published 21 January 2016).
23. Henriksen et al. teach antibodies and bispecific antibodies which bind TREM-1 having a modified constant region, wherein the TREM-1 antibodies bind an epitope comprising D38-F48 of human TREM-1, and comprise a heavy chain of SEQ ID NO:18, which shares 100% sequence identity to SEQ ID NO:14 of the instant claims (including the recited CDRs in claim 10) or a light chain which comprises SEQ ID NO:5 which shares 100% sequence identity to SEQ ID NO:15 (including the recited CDRs in claim 14) (See pg. 14, pg. 19). Henriksen also discloses conjugates comprising said antibody and an agent (See pg. 13), as well as compositions comprising said antibody and a carrier (See pg. 22). It is noted that the limitation of “an instructions for use” (claim 55) has not been given patentable weight (See In re Ngai, 367 F.3d 1336, 70 USPQ2d 1862 (Fed. Cir. 2004); MPEP 211.05IA). Thus, the Henriksen reference meets all the limitations of claims 1, 5, 10, 14, 49 and 53-55.
Claim Rejections - 35 USC § 103
24. 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.
25. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
26. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
27. Claim 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Henriksen et al. as applied to claims 1, 5, 10, 14, 49 and 53-55 above, and further in view of Strohl (Curr. Opin. Biotech. 2009. 20:685-691).
28. The teachings of Henriksen et al. are summarized above. Henriksen et al. does not teach wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of K214R, L234A, L235E, G237A, D356E, and L358M, per EU numbering; (ii) wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of K214R, L234A, L235E, G237A, A330S, P331S, D356E, and L358M, per EU numbering, (iii) wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of K214R, C226S, C229S, and P238S, per EU numbering, or (iv) wherein the IgG1 heavy chain constant region comprises one or more amino acid substitutions selected from the group consisting of S131C, K133R, G137E, G138S, Q196K, 1199T, N203D, K214R, C226S, C229S, and P238S.
29. However, such modifications in the IgG1 heavy chain of therapeutic antibodies were known at the time was filed. For example, Strohl discloses therapeutic antibodies comprising modification of the IgG1 heavy chain, including C226S, C229S, L234A and P238S (See Table 2 at pg. 688).
30. Therefore, it would have been obvious at the time the invention was filed to modify the TREM-1 antibodies taught by Henriksen to include the modifications of the IgG1 as disclosed in Strohl. The motivation to do so is disclosed by Henriksen et al. (See pg. 14) and Strohl (See pg. 685), that both disclose that modification of the IgG1 heavy chain are advantageous for therapeutic antibodies. The expectation of success is high since therapeutic antibodies comprising a modified IgG1 heavy chain are well-known in the art. Thus, the claims 6, 10 and 14 are prima facie obvious over the combined teachings of the prior art.
Double Patenting
31. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
32. Claims 1, 5-6, 10, 14, 49 and 53-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-25 of U.S. Patent No. 11,155,618. Although the conflicting claims are not identical, they are not patentably distinct from each other because the genus of antibodies recited in the instant claims is encompassed the species of antibodies recited in claims 4-25 of the’618 patent. The claims of the ‘618 patent also recite immunoconjugates, compositions, and kits comprising said antibody. Therefore, the claims are overlapping in scope.
Summary
33. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jon M. Lockard whose telephone number is (571) 272-2717. The examiner can normally be reached on Monday through Friday, 8:00 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached on (571) 272-2911. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JON M LOCKARD/
Examiner, Art Unit 1647
October 17, 2025