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 .
Claim Status
Applicant’s amendments and remarks, filed 02/25/2026, are acknowledged.
Claims 2-16, 18, 22-27, 30-45, 47-48, 50-58, 60-64, 66, 68-98, 100-108, 110-115, and 117-134 are canceled.
Claims 1, 17, and 21 are amended.
Claims 1, 17, 19-21, 28, 29, 46, 49, 59, 65, 67, 99, 109, 116, and 135-142 are pending.
Claims 49, 59, 65, 67, 99, 109, 116, and 137-142 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/30/2025.
As such, claims 1, 17, 19-21, 28, 29, 46, 135, and 136 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/25/2026 has been entered.
Withdrawn Rejections
Applicant’s arguments, see page 8, filed 02/25/2026, with respect to claims 17 and 21 rejected under 35 USC 112(d) as allegedly being of improper dependent form have been fully considered and are persuasive. The issue regarding improper dependent subject matter have been sufficiently addressed through amendments to the claim(s). As such, the rejection under 35 USC 112(d) is withdrawn.
Applicant’s arguments, see page 8, filed 02/25/2026, with respect to claims 17 and 21 rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. As such, the rejection under 35 USC 112(b) is withdrawn.
Maintained Rejections
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.
Claims 1, 17, 19-21, 28, 29, 46, 135, and 136 are rejected under 35 U.S.C. 103 as being unpatentable over Burkly et al (WO 2008/118356 A2, publication date: 10/02/2008; previously submitted with the Office Action mailed 07/01/2025) and further in view of Li et al (WO 2019/001417 A1, publication date: 01/03/2019; referred to as ‘417; previously submitted with the Office Action mailed 07/01/2025) and Li et al (US 2019/0184026 A1, publication date: 06/20/2019; referred to as ‘026; previously submitted with the Office Action mailed 07/01/2025), as evidenced by Vafa et al (Methods, Volume 65, Issue 1, 2014, Pages 114-126; previously submitted with the Restriction Requirement mailed 01/30/2025).
With respect to instant claims 1, 19-20, and 29, Burkly et al disclose of binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein (see Abstract). This includes humanized antibodies comprising VH and VL sequences (see Abstract and Fig. 12). Particularly, Burkly et al disclose of an isolated anti-CD154 antibody comprising SEQ ID Nos: 63 and 66 (see [0036], [0067]-[0068], [0173], Example 3, Figures 13 and 14). SEQ ID NO: 63 of Burkly shares 100% identity with instant SEQ ID Nos: 66 and 196, and SEQ ID NO: 66 of Burkly shares 100% identity to instant SEQ ID NO: 64 (see alignment below). Consequently SEQ ID Nos: 63 and 66 comprise the CDR sequences of the instant claim 1.
Instant SEQ ID NO: 64 Alignment
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Instant SEQ ID NO: 66 Alignment
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594
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Instant SEQ ID NO: 196 Alignment
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With respect to claims 1 and 21, Burkly et al disclose that the anti-CD154 antibodies may be engineered to elicit reduced effector function (see [0048]). Particularly, Burkly et al disclose of anti-CD154 antibodies comprising an IgG4 Fc region wherein the Fc region comprises an S228P mutation (see [0051], [0057], and Fig. 14). Burkly et al disclose that the claimed antibodies comprise of a lower hinge region consisting of residues 233-235 (see [0198]), and the lengths and flexibility of the hinge of the Fc region determines the binding affinity for FcR for the IgG4 antibodies (see [0219]). Burkly et al disclose that the claimed antibodies comprise an IgG4 framework wherein the Ala-Ala mutation would describe a mutation(s) from phenylalanine to alanine at position 234 and/or a mutation from leucine to alanine at position 235 (see [0213]). Burkly et al disclose that Fab fragments of the anti-CD154 antibodies is modified by the addition to the C-terminal end of its heavy chain one or more amino acids to allow the attachment of a functional moiety; preferably, the additional amino acids form a modified hinge region containing one or more cysteine residues to which the functional moiety may be attached (see [0283]). The functional moiety can be the human constant domain (i.e., human IgG4 Fc domain) (see [0389]).
Further with respect to claim 21, Figure 17 demonstrate that the anti-CD154 antibodies can be diFab’ fragments comprising the VH and VL, CH1 domains, and hinge regions. Particularly, Figure 17 shows the CH1 domain is on the C-terminal end of the VH and on the N-terminal end of the hinge (see [0111]- [0112] and [0121]- [0123]).
Lastly, with respect to instant claim 46, Burkly et al disclose of pharmaceutical compositions comprising the anti-CD154 antibody and a pharmaceutically acceptable carrier (see [0070]).
Burkly et al, however, fails to disclose of claimed anti-CD154 antibodies wherein the Fc region comprises the amino acid sequence of SEQ ID NO: 23 or 42 as recited in instant claim 17; nor wherein the antibody comprises a heavy chain comprises SEQ ID NO: 151 or 165, or SEQ ID NO: 95 or 109 as recited in instant claims 28 and 135-136. This is remedied by ‘417 and ‘026.
With respect to instant claim 17, ‘026 discloses of linker peptides for constructing a fusion protein wherein the linker peptides comprise a flexible peptide and a rigid peptide (see Abstract). The ‘026 discloses that the linker peptides can more effectively eliminate mutual steric hindrance, decrease a reduction/loss of polymerization or activity resulting from improper folding of an active protein or a conformational change (see Abstract). Particularly, ‘026 discloses of a variant IgG4 Fc variant comprising a human IgG4 hinge, CH2, and CH3 regions containing Ser228Pro (S228P) and Leu235Ala (L235A) mutations (SEQ ID NO: 12), wherein the variant has reduced effector function (ADCC or CDC effect) and/or an enhanced binding affinity for the neonatal receptor FcRn (see [0029]). SEQ ID NO: 12 disclosed by ‘026 which shares 100% identity to instant SEQ ID NOs: 23 and 42 (see alignment below).
SEQ ID NO: 42 Alignment
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SEQ ID NO: 23 Alignment
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Additionally, with respect to instant claim 135, ‘417 teaches of immunotherapy for hepatocellular carcinoma (see entire document). ‘417 disclose of engineered IgG4 region for the claimed immunotherapy wherein the engineered IgG4 Fc region comprised of mutations that reduced binding to FcγR (see [0040], [0044], and [0050]). Particularly, Table 5 of ‘417 disclose of SEQ ID NO: 93 which is a IgG4 variant comprising mutations 228P and 235A. SEQ ID NO: 93 of ‘417 shares 100% identity to instant SEQ ID Nos: 95 and 109 (see alignment below).
SEQ ID NO: 95 Alignment
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SEQ ID NO: 109 Alignment
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While ‘417 is drawn to anti-PD-1 antibodies and not anti-CD154 antibodies as claimed in the instant application, it is known in the art that engineered human IgG4 Fc domains comprising S228P and L235A substitutions result in minimal effector function and conserved half-life as evidenced by Vafa et al (see pg. 115, left column). Particularly, Vafa et al disclose that the S228P substitution stabilizes the hinge of the IgG4 to prevent heavy chain exchange and F234A/L235A substitutions are known to reduce interactions with Fc gamma receptor I (see pg. 117, right column).
As such, it would have been obvious to one of skill in the art to combine the teachings of Burkly, ‘417, and ‘026 to develop the claimed isolated anti-CD154 antibody as described in the instant application. One of skill would have been motivated to combine the art because Burkly et al disclose of humanized, isolated anti-CD154 antibodies comprising engineered human IgG4 Fc domains that result in reduced effector function (see [0036], [0048], [0067], [0068], [0173], Example 3, Figures 12-14) and pharmaceutical compositions comprising said antibodies see [0070]). Particularly, Burkly et al disclose of anti-CD154 antibodies comprising an IgG4 Fc region wherein the Fc region comprises an S228P mutation (see [0051], [0057], and Fig. 14). Burkly et al disclose that Fab fragments of the anti-CD154 antibodies is modified by the addition to the C-terminal end of its heavy chain one or more amino acids to allow the attachment of a functional moiety; preferably, the additional amino acids form a modified hinge region containing one or more cysteine residues to which the functional moiety may be attached (see [0283]). The functional moiety can be the human constant domain (i.e., human IgG4 Fc domain) (see [0389]). Figure 17 demonstrate that the anti-CD154 antibodies can be diFab’ fragments comprising the VH and VL, CH1 domains, and hinge regions. Particularly, Figure 17 shows the CH1 domain is on the C-terminal end of the VH and on the N-terminal end of the hinge (see [0111]- [0112] and [0121]- [0123]). While Burkly does not disclose of the sequences recited in instant claims 17 and 135, it is known in the art that engineered human IgG4 Fc domains comprising S228P and L235A substitutions result in minimal effector function and conserved half-life as disclosed by ‘026 and evidenced by Vafa et al (see pg. 115, left column). Particularly, Vafa et al disclose that the S228P substitution stabilizes the hinge of the IgG4 to prevent heavy chain exchange and F234A/L235A substitutions are known to reduce interactions with Fc gamma receptor I (see pg. 117, right column).
Furthermore, with respect to instant SEQ ID Nos: 151 and 161 of claims 28 and 136, instant SEQ ID NO: 64 makes up amino acid positions 1-118 for instant SEQ ID Nos: 151 and 165; instant SEQ ID NO: 95 makes up amino acid positions 119-444 for instant SEQ ID NO: 151; instant SEQ ID NO: 109 makes up amino acid positions 119-445 for instant SEQ ID NO: 165; and, instant SEQ ID NO: 42 makes up amino acid positions 217-444 for instant SEQ ID NO: 151 or amino acid positions 217-445 for instant SEQ ID NO: 165 (see SEQ ID NO: 165 alignments below).
SEQ ID NO: 165 Alignment (SEQ ID NO: 64)
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SEQ ID NO: 165 Alignment (SEQ ID NO: 95)
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SEQ ID NO: 165 Alignment (SEQ ID NO: 109)
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SEQ ID NO: 165 Alignment (SEQ ID NO: 42)
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Therefore, the teachings of Burkly, ‘026, and ‘417 make the instant application prima facie obvious because one of skill in the art would have a reasonable expectation that combining the VH and VL sequences of Burkly with the Fc region and constant region of ‘026 and ‘417, respectively, would result in isolated anti-CD154 antibodies with conserved half-life and reduced effector function, thus allowing prolonged therapeutic benefits with reduced risk of unwanted side effects.
Applicant’s Arguments
Applicant traverses the 103 rejection (see pages 9-19 of the Remarks filed on 02/25/2026).
Solely to advance prosecution and without acquiescing to the Examiner assertions, Applicant has amended claim 1 (and, thus, claims 17, 19-21, 28, 29, 46, 135, and 136 depending directly or indirectly therefrom) to recite that the human Fc region derived from IgG4 and consisting essentially of S228P and L235A amino acid modifications according to EU numbering. A person of skill in the art would understand that the recitation of a human Fc region derived from IgG4 and consisting essentially of S228P and L235A amino acid modifications does not include additional mutations that affect Fc effector function but could comprise other mutations that do not affect Fc effector function.
The Examiner has acknowledged (Office Action at 3) that "Burkly does not specifically recite that the claimed anti-CD154 antibody comprises an IgG4 Fc domain comprising S228P and L235A amino acid modifications in tandem as recited in the instant claims" (emphasis original). The claimed antibodies represent an improvement over the variants of the 5c8 antibody disclosed in Burkly, such as the aglycosylated variant, which comprises the S228P mutation (see, Burkly paragraph [0088]), because it was known in the art at the effective filing date that aglycosylation mutations negatively affected the 5c8 antibody's performance. See, e.g., Burkly Figure 20. It was also known in the art at the effective filing date that aglycosylation versions of the 5c8 antibody resulted in a lack of efficacy in inhibiting or preventing transplant rejection in rhesus renal and islet allotransplantation models. See, paragraphs [0007] and [0016] in the application as filed; see also Ferrant et al. Int Immunol. 2004 Nov;16(11):1583-94 at 1586, right col.; submitted in the October 11, 2022 IDS; hereinafter "Ferrant")("Aglycosyl anti-CD154 is relatively ineffective in preventing islet allograft rejection")… Burkly discloses that an anti-CD154 antibody can be an IgG4 subtype containing the mutations S228P and L235E (PE mutation) in the heavy chain constant region. Burkly, however, does not disclose actually making or testing this variant and, therefore, would have provided the person of ordinary skill in the art with no information as to whether such an antibody would retain effector function. The instant application, however, generated and tested the PE mutation of Burkly as TNX08. As shown in Figure 12A of the instant application, TNX08 demonstrated 2638-fold weaker binding to FcyR1A as compared to wildtype 5c8 antibody (TNX02). Accordingly, the PE mutation of Burkly demonstrated even lesser effector function (via an FcyR binding assay) than the N297Q IgG1 agylcosyl variant that was shown in Ferrant to be unable to prevent transplant rejection. The Examiner also asserts that to Vafa demonstrates "that engineered human IgG4 Fc domains comprising S228P and L235A substitutions result in minimal effector function and conserved half- life." Contrary to the Examiner's assertions, however, Vafa only discusses the combination of the S228P, L234A3 and L235A mutations. See Vafa at 115, left col. ("IgG4 with S228P/L234A/L235A substitutions (IgG4 ProAlaAla)" (emphasis original). It never discusses the combination of S228P and L235A without an alanine substitution at residue 234. Additionally, Vafa discloses that "[w]ith regard to mutated versions of IgG4, specific affinity for FcyR has been eliminated by the L234A/L235A substitutions." See Vafa at 115, left col. (emphasis added). It was known in the art, however, that the effector functions of an anti-CD154 antibody are required to prevent transplant rejection. See Ferrant, supra. Accordingly, the person of ordinary skill in the art would not have had a reasonable expectation of success in modifying Burkly with Vafa because doing so would eliminate the effector functions required to prevent transplant rejection… Wang does not cure the defects of Burkly. While Wang discloses an IgG4 Fc region comprising the S228P and L235A substitutions, it does not provide any data demonstrating the effect those substitutions had on FcyR binding. Rather, Wang discloses that its anti-PD1 antibody "was specifically engineered to minimize FcyR binding." See, Wang, 1 [0002], [0005], and [0047] (emphasis added). Moreover, Wang discloses an IgG4 Fc region comprising S228P, 234A, and 235A substitutions (see Table 6, SEQ ID NO: 96), which Vafa disclosed eliminated FcyR binding… Li does not cure the defects of the combination of Burkly and Wang. Li discloses that "[t]he object of the present invention is to provide a novel peptide linker for constructing fusion proteins." See Li at [0008]. The fusion proteins disclosed in Li "comprise[] two biologically active molecules and a peptide linker linking the two active molecules." See Li [0025]. While Wang discloses an IgG4 Fc region comprising the S228P and L235A substitutions, it does not provide any data demonstrating the effect those substitutions had on FcyR binding. Indeed, the Examiner acknowledges Li's lack of data related to Fc binding by pointing to Vafa as evidence as to how the S228P and L235A substitutions would be expected to perform. See Office Action at 11… In its October 3, 2025 Amendment and Reply, Applicant demonstrated that Wang and Li do not contain any disclosure related to anti-CD154 antibodies and, therefore, do not address the knowledge in the art regarding the propensity of such antibodies to cause thrombosis or the requirement of effector function for such antibodies to prevent… The instant application, however, demonstrates that the claimed antibodies prevented the rejection of a heart transplant. See Example 8. Specifically, a heterotopic heart transplantation was performed in a Cynomolgus macaque monkey, who subsequently received the claimed antibodies. No sign of rejection was detected through Day 84 of the study, nor was any sign of thrombosis or thromboembolic events. Id. By contrast, Ferrant disclosed that transplant rejection was seen after six days (islet transplant) or seven days (kidney transplant) in primates treated with anti-CD154 antibodies comprising substitutions in the Fc region to reduce/eliminate effector function.
Response to Arguments
Applicant's arguments filed 02/25/2026 have been fully considered but they are not persuasive.
Examiner acknowledges the amendments to the claims. However, amending the claim from “comprising” to “consisting essentially of” does not remedy the rejection. First, MPEP 2111.03(III) indicates that the transitional phrase “consisting essentially of” occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format" which limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. Absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." Thus, the claims are construed as equivalent to “comprising” because the art teaches the limitations of the claims. Secondly, it is noted that the features upon which applicant relies (i.e., additional mutations that affect Fc effector function but could comprise other mutations that do not affect Fc effector function) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claims do not require that the isolated antibody have any function other than bind to CD154 and comprise a human IgG4 Fc region with S228P and L235A substitutions. The examined claims do not require that the Fc region have any functions. Therefore, the claims are not limited to an Fc region with only S228P and L235A substitutions.
Additionally, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Burkly et al disclose of humanized, isolated anti-CD154 antibodies comprising engineered human IgG4 Fc domains that result in reduced effector function (see [0036], [0048], [0067], [0068], [0173], Example 3, Figures 12-14) and pharmaceutical compositions comprising said antibodies see [0070]). Particularly, Burkly et al disclose of anti-CD154 antibodies comprising an IgG4 Fc region wherein the Fc region comprises an S228P mutation (see [0051], [0057], and Fig. 14). Burkly et al disclose that Fab fragments of the anti-CD154 antibodies is modified by the addition to the C-terminal end of its heavy chain one or more amino acids to allow the attachment of a functional moiety; preferably, the additional amino acids form a modified hinge region containing one or more cysteine residues to which the functional moiety may be attached (see [0283]). The functional moiety can be the human constant domain (i.e., human IgG4 Fc domain) (see [0389]). Figure 17 demonstrate that the anti-CD154 antibodies can be diFab’ fragments comprising the VH and VL, CH1 domains, and hinge regions. Particularly, Figure 17 shows the CH1 domain is on the C-terminal end of the VH and on the N-terminal end of the hinge (see [0111]- [0112] and [0121]- [0123]). While Burkly does not disclose of the sequences recited in instant claims 17 and 135, it is known in the art that engineered human IgG4 Fc domains comprising S228P and L235A substitutions result in minimal effector function and conserved half-life as disclosed by ‘026 and evidenced by Vafa et al (see pg. 115, left column). Particularly, Vafa et al disclose that the S228P substitution stabilizes the hinge of the IgG4 to prevent heavy chain exchange and F234A/L235A substitutions are known to reduce interactions with Fc gamma receptor I (see pg. 117, right column). Thus, one of skill in the art would have a reasonable expectation that combining the VH and VL sequences of Burkly with the Fc region and constant region of ‘026 and ‘417, respectively, would result in isolated anti-CD154 antibodies with conserved half-life and reduced effector function, thus allowing prolonged therapeutic benefits with reduced risk of unwanted side effects.
Furthermore, Burkly indicated that S228P and T299A in tandem were aglycosylation mutations, not S228P mutation independently (see [0088], [0090], [0388], and [0389]). Additionally, with respect to Applicant’s argument that Vafa discloses that "[w]ith regard to mutated versions of IgG4, specific affinity for FcyR has been eliminated by the L234A/L235A substitutions”, the art teaches that S228P/L234A/L235A mutations in IgG4 bind to FcγR as evidenced by Tables 1-3 and 5 of Strohl et al (EP2506871 B1, publication date: 10/19/2016). As such, in terms of the “consisting essentially of”, the art confirms that additional mutations (such as L234A) maintains FcyR binding.
Lastly, it is noted that the features upon which applicant relies (i.e., the claimed anti-CD154 antibody preventing transplant rejection) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As stated above, the claims do not require that the isolated antibody have any function other than bind to CD154 and comprise a human IgG4 Fc region with S228P and L235A substitutions. The examined claims do not require that the Fc region have any functions. Therefore, the claims are not limited to an Fc region with only S228P and L235A substitutions.
As such, the 103 rejection is maintained.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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18/271,098
Claims 1, 17, 19-21, 28, 29, 46, 135, and 136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-13, 30-33, 41-42, 49, 52-60, and 63-64 of copending Application No. 18/271,098 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘098 application is drawn to a method of inducing immune tolerance in a transplant recipient, the method comprising administering to the recipient one or more doses of an isolated anti-CD 154 antibody, transplanting into the recipient hematopoietic stem cells, and transplanting a donor organ, a donor tissue or donor cell into the recipient, wherein the hematopoietic stem cells produce immune cells that are tolerant of the donor organ, donor tissue or donor cell, thereby inducing immune tolerance in the recipient; wherein the isolated anti-CD154 antibody comprises a humanized variable domain, wherein the variable domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein the VH is operably linked to a human Fc region derived from IgG4 and comprising S228P and L235A amino acid modifications; wherein the VH comprises:(a) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 57,(b) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 58, and (c) a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 59; and wherein the VL comprises:(a) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 60,(b) a light chain CDR2 having the amino acid sequence of SEQ ID NO: 61, and(c) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 62 (see claim 1). Particularly, the ‘098 claims are drawn to the method of claim 1, wherein the Fc region comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 23 or 42 (see claim 30); wherein the heavy chain comprises a constant region comprising the amino acid sequence of SEQ ID NO: 95 or 109 (see claim 31); wherein the VH comprises the amino acid sequence of SEQ ID NO: 64 (see claim 32); wherein the VL comprises the amino acid sequence of SEQ ID NO: 66 (see claim 33); wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 151 or 165 (see claim 41); and, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 196 (see claim 42). The sequences recited in the ‘098 application share 100% identity with the corresponding sequences of the present application (e.g., SEQ ID NO: 64 of the ‘098 application shares 100% identity to instant SEQ ID NO: 64).
The difference between the instant application and the ‘098 application is that the instant application is drawn to a composition whereas the ‘098 application is drawn to a method of using the composition. However, the Federal Circuit has held that obviousness-type double patenting exists for method claims that simply claim the disclosed use of a composition in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). The instant application and the copending application are not divisional applications resulting from restriction, and therefore no protection under the provisions of 35 USC 121. As such, the present invention as a whole is prima facie obvious to one of ordinary skill in the art in view of the ‘098 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments
Applicant asserts that this application has a patent term filing date of July 1, 2020. The ‘098 application has a patent term filing date of January 6, 2022. Accordingly, to the extent the only rejection remaining in this application (i.e., the application having the earlier patent term filing date) is the provisional non-statutory double patent rejection, Application requests that the Examiner withdraw this rejection and permit this application to issue as a patent. M.P.E.P. § 804(I)(B)(1)(b)(i). (See pages 19 and 20 of the Remarks filed on 02/25/2026).
Response to Arguments
Applicant's arguments filed 02/25/2026 have been fully considered but they are not persuasive. Applicant is reminded that a rejection under double patenting precludes the identification of allowable subject matter. Applicant has not filed a terminal disclaimer, and the claims remain rejected for reasons set forth above.
The Examiner acknowledges that MPEP 1490 states that if the provisional ODP rejections in both applications are the only rejections remaining in those applications, the examiner should then withdraw the provisional ODP rejection in the earlier-filed application thereby permitting that application to issue without need of a terminal disclaimer. The instant application has an effective filing date of July 1, 2019, while the copending application has an effective filing date of January 6, 2021. The instant application is therefore the earlier filed application. Further, as indicated above, the provisional double patenting rejection is not the only rejection remaining, and therefore the rejection is maintained.
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As such, the provisional double patenting rejection is maintained.
Conclusion
No claims are allowed.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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