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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-3, 7, 9, 14, 15 and 23) in the reply filed on 07/10/2026 is acknowledged. Claims 17, 18, 24, 29, 36, 38, 39, 42, 44, 48, 51 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/10/2026.
Claims 1-3, 7, 9, 14, 15 and 23 are under examination.
Drawings
The drawings are objected to because Figures 1-7 contain color drawings and there has been no granted petition to include color drawings in this application. 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. 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).
More specifically, 37 C.F.R. 1.84(a)(2) states:
On rare occasions, color drawings may be necessary as the only practical medium by which to disclose the subject matter sought to be patented in a utility patent application…The Office will accept color drawings in utility patent applications only after granting a petition filed under this paragraph explaining why the color drawings are necessary. Any such petition must include the following:
(i) The fee set forth in § 1.17(h);
(ii) One (1) set of color drawings if submitted via the Office electronic filing system, or three (3) sets of color drawings if not submitted via the Office electronic filing system; and
(iii) An amendment to the specification to insert (unless the specification contains or has been previously amended to contain) the following language as the first paragraph of the brief description of the drawings:
The patent or application file contains at least one drawing executed in color. 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.
(Emphases added.) MPEP 608.02, part VIII, states:
Color drawings and color photographs are not accepted in utility applications filed under 35 U.S.C. 111 unless a petition filed under 37 CFR 1.84(a)(2) or (b)(2) is granted. Color drawings and color photographs are not permitted in international applications (see PCT Rule 11.13).
Unless a petition is filed and granted, color drawings or color photographs will not be accepted in a utility patent application filed under 35 U.S.C. 111. The examiner must object to the color drawings or color photographs as being improper and require applicant either to cancel the drawings or to provide substitute black and white drawings.
Priority
Applicant’s claim for the benefit of a prior-filed application under is acknowledged. The subject matter defined in the instant claims is not supported by the disclosure in provisional application serial no. 63/329,551 because at least SEQ ID NOs: 1 and 3 are not disclosed in the ‘551 provisional. For instance, see the alignment between SEQ ID NO: 1 of the ‘551 provisional and instant SEQ ID NO: 1:
Query Match 69.8%; Score 1946; DB 1; Length 555;
Best Local Similarity 70.9%;
Matches 398; Conservative 28; Mismatches 89; Indels 46; Gaps 9;
Qy 1 MKWVTFISLLFLFSSAYSASEDTIIGFLGOPVTLPCHYLSWSOSRNSMCWGKGSCPNSKC 60
||||||||||||||||| || : || ||||| | ||| : ||||||| || | |
Db 1 MKWVTFISLLFLFSSAY--SETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGC 58
Qy 61 NAELLRTDGTRIISRKSTKYTLLGKVOFGEVSLTISNTNRGDSGVYCCRIEVPGWFNDVK 120
|:|||| |: |||| || | | : |:||||| | : |||||||||||||||||||
Db 59 KEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVK 118
Qy 121 KNVRLELRR--------ATTTKKPTTTTRPTTTPYVTTTTPELLPTTVMTTSVLPTTTPP 172
|||| |:| |||| : |||| |||| : |||| |||||:|| | | ||
Db 119 INVRLNLQRASTTTHRTATTTTRRTTTTSPTTTRQM-TTTPAALPTTVVTTPDLTTGTPL 177
Qy 173 OTLATTAFSTAVTTCPSTTPGSFSOETT---------KGSAFTTESET-LPASNHSORSM 222
: |:|| || | || : :| | :| | |||| ||: : | |:
Db 178 QMTTIAVFTTA-NTCLSLTPSTLPEEATGLLTPEPSKEGPILTAESETVLPSDSWS--SV 234
Qy 223 MTISTDIAVLRPTGSNPGILPSTSOLTTOKTTLTTSE-----------SLOKTTKSHQIN 271
: | | :| | ||||| :: ||: : | ||||: |::
Db 235 ESTSADTVLLTSKESKVWDLPSTSHVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMD 294
Qy 272 S-----------RQTGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQA 320
| |||||||||||||||||||||||||||||||||||||||||||||
Db 295 GIPMSMKNEMPISQLGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQA 354
Qy 321 PGKGLEWVAVIWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQM 380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 355 PGKGLEWVAVIWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQM 414
Qy 381 GYWHFDLWGRGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQ 440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 415 GYWHFDLWGRGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQ 474
Qy 441 SVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYY 500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 475 SVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYY 534
Qy 501 CQQRSNWPPLTFGGGTKVEIK 521
|||||||||||||||||||||
Db 535 CQQRSNWPPLTFGGGTKVEIK 555
Thus, the priority date of claims 1-3, 7, 9, 14, 15 and 23 of the instant application is 4/11/2023, the filing date of PCT/US2023/065619.
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claims 1-3, 7, 9, 14, 15 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (WO 2020/047473—on IDS filed 03/26/2025), in view of Hoo et al. (US 2005/0276756—on IDS 03/26/2025) and Ho et al. (US2015/0118252—on IDS filed 03/26/2025). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Wong teaches “a single-chain chimeric [i.e., fusion] polypeptide comprising a first target-binding domain, a linker domain, and a second target-binding domain”, wherein the first target binding domain may be TIM-4, wherein the second target-binding domain may be an scFv that binds CD3 (p. 2, In 16-17; p. 3, In 17-18; claims 34-35; p. 4, lines 17-26). Wong teaches the anti-CD3 scFv has six CDRs (see p. 195, lines 26-27). Wong teaches that the “single chain chimeric polypeptide further includes a signal sequence at its N-terminal end” (see p. 10, lines 1-2) and that “a signal sequence…directs the protein to the secretory pathway” (see p. 227, lines 12-18). The signal sequence disclosed in Wong is MKWVTFISLLFLFSSAYS, which shares 100% sequence identity with instant SEQ ID NO: 2 (see p. 227, line 24). Wong also teaches the common linker sequence, GGGGS (see p. 150, lines 29-30) and contemplates that the chimeric polypeptides may include a peptide tag (see pages 232, line 17 through p. 238, line 5). Wong teaches that the single-chain chimeric polypeptides can be formulated as compositions with pharmaceutically acceptable excipients (see p. 439, lines 1-14). Wong also teaches constructs comprising a promoter operably linked to a polynucleotide encoding the single chain chimeric polypeptides, and that the constructs may be lentiviral, retroviral or an AAV vector (see p. 440, line 8 through p. 441, line 8).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Wong does not teach that the TIM-4 sequence comprises SEQ ID NO: 3 or that the anti-CD3 scFv comprises the six CDRs set forth in SEQ ID NOs: 22-27. These issues are considered in turn.
Hoo et al. (US2005/0276756) teach compositions comprising an antigen and a TIM targeting molecule, wherein said TIM targeting molecule may be a TIM-4 domain comprising 100% sequence identity to instant SEQ ID NO: 3 (see abstract; paragraph [0041]). The alignment between instant SEQ ID NO: 3 and SEQ ID NO: 41 of Hoo and colleagues is as follows:
Query Match 100.0%; Score 1519; DB 1; Length 378;
Best Local Similarity 100.0%;
Matches 291; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 25 ETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKY 84
Qy 61 RLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVKINVRLNLQRASTTTHRTATT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 85 RLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVKINVRLNLQRASTTTHRTATT 144
Qy 121 TTRRTTTTSPTTTRQMTTTPAALPTTVVTTPDLTTGTPLQMTTIAVFTTANTCLSLTPST 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 145 TTRRTTTTSPTTTRQMTTTPAALPTTVVTTPDLTTGTPLQMTTIAVFTTANTCLSLTPST 204
Qy 181 LPEEATGLLTPEPSKEGPILTAESETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 205 LPEEATGLLTPEPSKEGPILTAESETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTS 264
Qy 241 HVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMDGIPMSMKNEMPISQL 291
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 265 HVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMDGIPMSMKNEMPISQL 315
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to use the TIM-4 sequence as taught in Hoo et al. because TIM-4 is capable of stimulating an immune response (see abstract; paragraph [0180] of Hoo and colleagues), which would be useful in developing a composition. The person of ordinary skill in the art would have been motivated to use the human TIM-4 allele 2 because it was a known sequence and one would be motivated to use a human TIM-4 when developing a composition for human use. Express suggestion to substitute one equivalent for another need not be present to render such a substitution obvious (see MPEP 2143(I)(B)).
Ho et al. (US2015/0118252) disclose a humanized minibody comprises a polypeptide that comprises a single-chain variable fragment (scFv) that binds to CD3 (see paragraphs [0007]; [0098]). The sequence of the anti-CD3 scFv disclosed by Ho and colleagues shares 97% sequence homology to instant SEQ ID NO: 5 and encompasses the six CDRs that share 100% sequence identity with instant SEQ ID NOs: 22-27 (shown bolded and underlined in alignment):
Query Match 97.9%; Score 1255.5; DB 1; Length 395;
Best Local Similarity 97.5%;
Matches 238; Conservative 0; Mismatches 3; Indels 3; Gaps 1;
Qy 1 QVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQAPGKGLEWVAVIWYDGSKKYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 QVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQAPGKGLEWVAVIWYDGSKKYY 80
Qy 61 VDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQMGYWHFDLWGRGTLVTVSSG- 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 VDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQMGYWHFDLWGRGTLVTVSSGS 140
Qy 120 --GGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP 177
||||||| ||| |||||||||||||||||||||||||||||||||||||||||||||
Db 141 TSGGGSGGGSGGGGSSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP 200
Qy 178 RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPLTFGGGTK 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPLTFGGGTK 260
Qy 238 VEIK 241
||||
Db 261 VEIK 264
It would have been obvious to one of ordinary skill in the art to have applied the anti-CD3 scFv sequence disclosed by Ho and colleagues because it was known in the art and could have been applied during the ordinary course of experimentation. Express suggestion to substitute one equivalent for another need not be present to render such a substitution obvious (see MPEP 2143(I)(B)).
The combined teachings of Wong, Hoo et al. and Ho et al. render obvious the fusion protein comprising SEQ ID NO: 1 or sequences with at least 90% identity to SEQ ID NO: 1 because Wong teaches the overarching structure of a fusion protein comprising a TIM-4 domain linked to a single chain variable fragment (scFv) anti-CD3 along with a signal sequence identical to SEQ ID NO: 2 and a Gly-Ser linker sequence (GGGGS), Hoo et al. teach a TIM-4 domain comprising the same sequence as set forth in SEQ ID NO: 3 and Ho et al. teach an anti-CD3 scFv specific comprising a sequence with 97.9% identity to SEQ ID NO: 5 and 100% identity to SEQ ID NOs: 22-27. Instant SEQ ID NO: 1 consists of from the N to C terminus: SEQ ID NO: 2 – SEQ ID NO: 3 – linker (GGGGS) – SEQ ID NO: 5, therefore, the combined prior art taught each of these elements. The person having ordinary skill in the art, upon reading the combined prior art references would merely be choosing from a finite number of identified, predictable elements and substituting one known element for another to obtain predictable results. Further, as noted by the United States Supreme Court, if a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. “When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product is not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show it was obvious under 35 U.S.C. 103.” KSR Int'l Co. v. Teleflex Inc., 127 S.Ct. 1727, 1742, 82USPQ2d 1385, 1396 (2007).
Thus, the claims do not contribute anything non-obvious over the prior art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Corey et al. (WO2022/036265) teach chimeric TIM-4 proteins attached to a CD3ζ signaling domain (see Figure 1A). Corey et al. also teach the TIM-4 protein has the same sequence as set forth in instant SEQ ID NO: 3. See the alignment between instant SEQ ID NO: 3 and SEQ ID NO: 1 of Corey and colleagues:
Query Match 100.0%; Score 1519; DB 1; Length 378;
Best Local Similarity 100.0%;
Matches 291; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 25 ETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKY 84
Qy 61 RLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVKINVRLNLQRASTTTHRTATT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 85 RLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVKINVRLNLQRASTTTHRTATT 144
Qy 121 TTRRTTTTSPTTTRQMTTTPAALPTTVVTTPDLTTGTPLQMTTIAVFTTANTCLSLTPST 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 145 TTRRTTTTSPTTTRQMTTTPAALPTTVVTTPDLTTGTPLQMTTIAVFTTANTCLSLTPST 204
Qy 181 LPEEATGLLTPEPSKEGPILTAESETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 205 LPEEATGLLTPEPSKEGPILTAESETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTS 264
Qy 241 HVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMDGIPMSMKNEMPISQL 291
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 265 HVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMDGIPMSMKNEMPISQL 315
Corey et al. teach that “Tim4-induced Tim1 signaling has been found to co-stimulate T cell proliferation and survival…[thus] cytotoxic chimeric Tim receptors may reduce or inhibit T cell exhaustion, or restore exhausted T cells by providing costimulatory signals via at least one signaling pathway (p. 6, lines 20-26).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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