DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive.
Claims 1-49 and 51 have been cancelled. Claims 50 and 52-56 are under consideration.
The instant application is a continuation of application 14/128,681. As set forth in prior Office actions, the lack of unity requirement in parent application 14/128,681 (mailed 2/6/2015) had four groups:
Group I, claims 1-6 and 29-34, drawn to proteins and pharmaceutical compositions comprising them.
Group II, claims 7-23, drawn to a first method of prediction.
Group III, claims 24-28, drawn to a second method of predictions.
Group IV, claims 35-36, drawn to a method of treatment.
None of the groups from parent application 14/128,681 reflect the methods of the instant claims.
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 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.
The inventorship of the instant application is Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer. The applicants are Ablynx N.V. and Sanofi. (See 9/15/2022 filing receipt.)
(1) Claims 50 and 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, and 22-23 of U.S. Patent No. 11,220,539 (applicant Ablynx N.V.; inventors Buyse and Boutton) in view of Borras et al. (WO 2011/075861, of record). The ’539 patent has inventors Buyse and Boutton and applicant Ablynx NV in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 12, and 22-23 of the ‘539 patent are reproduced below:
1. A method of modifying an immunoglobulin single variable domain (VH or VHH) to have reduced binding by pre-existing antibodies found in human blood or serum, the method comprising mutating the amino acid sequence of the immunoglobulin single variable domain to generate a modified immunoglobulin single variable domain comprising the amino acid V at position 11 and the amino acid L at position 89, wherein the positions are numbered according to Kabat numbering; wherein, prior to mutation, the immunoglobulin single variable domain comprises: (i) an amino acid other than V at position 11 and an amino acid other than L at position 89; (ii) an amino acid V at position 11 and an amino acid other than L at position 89; or (iii) an amino acid other than V at position 11 and an amino acid L at position 89.
12. The method of claim 1, further comprising extending the C-terminal end of said immunoglobulin single variable domain by 1 to 5 amino acid residues.
22. A method of modifying an immunoglobulin single variable domain (VH or VHH) to have reduced binding to its C-terminal end by pre-existing antibodies found in human blood or serum, the method comprising mutating the amino acid sequence of the immunoglobulin single variable domain at position 11, at position 89, or at positions 11 and 89 to generate a modified immunoglobulin single variable domain comprising the amino acid V at position 11 and the amino acid L at position 89, wherein the positions are numbered according to Kabat numbering.
23. The method of claim 22, further comprising extending the C-terminal end of said immunoglobulin single variable domain by 1 to 5 amino acid residues.
It is noted that the naturally occurring, unmutated C-terminal end of an ISV would have been known by those of ordinary skill in the art to end in the sequence VTVSS. Instant claim 50 has the same positive active steps of extending the C-terminal as in the issued claims while the intention of reducing protein interference is positively recited in its preamble. The limitations of instant claim 54 are present in the referenced issued claims.
With respect to instant claims 52-53, the recitation of “extending the C-terminal end of said immunoglobulin single variable domain by 1 to 5 amino acid residues” in the issued claims would immediately suggest C-terminal extensions such as alanine (A), glycine (G), and alanine-glycine (AG) to one of ordinary skill in the art, particularly when the issued claims are read in light of the ‘539 specification. See in particular the ‘539 abstract. These endings are within the scope of issued claims and would have been obvious in view of the issued claims.
The claims are not patentably distinct.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(2) Claims 50 and 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,009,511 (applicant Ablynx N.V; inventors Snoeck, Buyse, and Baumeister). The ’511 patent has inventors Snoeck, Buyse and Baumeister and applicant Ablynx NV in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 2, and 7 of the ‘511 patent are reproduced below:
1. Method for detecting and/or measuring in a sample anti-drug antibodies that bind to a polypeptide that comprises at least one variable domain of the heavy chain of a heavy-chain antibody (VHH domain), humanized VHH domain, or camelized heavy chain variable domain of a conventional antibody (VH domain) with an exposed C-terminal region with the sequence VTVSS (SEQ ID NO: 1), said method comprising at least the steps of: a) contacting said sample with a capturing agent that is immobilized on a support, wherein said capturing agent is or essentially consists of said polypeptide, under conditions such that anti-drug antibodies against said polypeptide can bind to said capturing agent to form a complex of the capturing agent and any captured anti-drug antibodies; b) optionally removing any components or constituents present in said sample that do not bind to the capturing agent; c) detecting or measuring any anti-drug antibodies that have bound to the capturing agent, by contacting the complex of the capturing agent and the captured anti-drug antibodies with a detection agent, under conditions such that said detection agent can bind to the complex of the capturing agent and the captured anti-drug antibodies, wherein said detection agent is or essentially consists of: (i) said polypeptide; (ii) a detectable tag or label bound to said polypeptide either directly or via a suitable linker and (iii) 1-5 amino acid residues that are linked to the exposed C-terminal end with sequence VTVSS (SEQ ID NO: 1) of the VHH domain, humanized VHH domain, or camelized VH domain, in which said sample is a sample of whole blood, serum, plasma, ocular fluid, bronchoalveolar fluid/bronchoalveolar lavage fluid (BALF), cerebrospinal fluid or another biological fluid.
2. Method according to claim 1, in which the detection agent has the amino acid sequence VTVSS(X)n (SEQ ID NO:2) at its C-terminal end, in which n is 1 to 5; and in which each X is a naturally-occurring amino acid residue that is independently chosen.
7. Method according to claim 2, wherein each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
The detection agent having 1-5 amino acid residues that are linked to the exposed C-terminal end with sequence VTVSS of the VHH domain, humanized VHH domain, or camelized VH domain of the issued claims corresponds to the modified ISV of the instant claims. This detection agent has been modified in the issued claims as required by the instant claims. Issued claim 1 meets the limitations of claims 50. The limitations of instant claim 54 are present in issued claim 1. The limitations of instant claims 52-53 are present in issued claims 2 and 7.
The claims are not patentably distinct.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(3) Claims 50 and 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,553,901.
This rejection corresponds to the double patenting rejection set forth in the prior Office action over claims 1, 3-5, 8, 13, and 15-18 of copending Application No. 17/229,119 (7/29/2025 claim set) (applicant Ablynx N.V.; inventors Snoeck, Buyse, and Baumeister). Application No. 17/229,119 issued as U.S. Patent No. 12,553,901 on 17 February 2026. This is not a new ground of rejection.
The ’901 patent has inventors Snoeck, Buyse, and Baumeister and applicant Ablynx NV in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01. Although the claims at issue are not identical, they are not patentably distinct from each other.
Issued claims 1-4 and 9-10 are reproduced below.
1. Method for detecting and/or measuring in a sample treatment-emergent anti-drug antibodies that bind to a polypeptide that comprises at least one variable domain of the heavy- chain antibody (VHH domain), humanized VHH domain, or camelized heavy chain variable domain of a conventional antibody (VH domain) with an exposed C-terminal region with the sequence VT VSS (SEQ ID NO: 1), said method comprising at least the steps of:
a) contacting said sample with a capturing agent that is immobilized on a support; under conditions such that treatment-emergent anti-drug antibodies against said polypeptide can bind to said capturing agent to form a complex of the capturing agent and any captured treatment-emergent anti-drug antibodies;
b) optionally removing any components or constituents present in said sample that do not bind to the capturing agent;
c) detecting or measuring any treatment-emergent anti-drug antibodies that have bound to the capturing agent, by contacting the complex of the capturing agent and the captured treatment-emergent anti-drug antibodies with a detection agent, under conditions such that said detection agent can bind to the complex of the capturing agent and the captured treatment-emergent anti-drug antibodies,
wherein said capturing agent is or essentially consists of: (i) said polypeptide; and (ii) 1- 5 amino acid residues that are linked to the exposed C-terminal region with sequence VTVSS (SEQ ID NO: 1) of the VHH domain, humanized VHH domain, or camelized VH domain,
in which said sample is a sample of whole blood, serum, plasma, ocular fluid, bronchoalveolar fluid (BALF), cerebrospinal fluid or other biological fluid, and wherein said sample has been obtained from a subject to which said polypeptide, or a compound or molecule comprising said polypeptide, has been administered according to a regimen that is such that there is a risk or possibility that treatment-emergent anti-drug antibodies against said polypeptide have been raised in the subject.
2. Method according to claim 1, in which the capturing agent has the amino acid sequence VTVSS(X)n (SEQ ID NO: 2) at its C-terminal end, in which n is 1 to 5; and in which each X is a naturally occurring amino acid residue that is independently chosen.
3. Method according to claim 1, in which said detection agent is or essentially consists of: (1) said polypeptide; (ii) a detectable tag or label bound to said polypeptide either directly or via a suitable linker; and (iii) 1-5 amino acid residues that are linked to the exposed C-terminal region with sequence VT VSS (SEQ ID NO: 1) of the VHH domain, humanized VHH domain, or camelized VH domain.
4. Method according to claim 1, in which the detection agent has the amino acid sequence VTVSS(X)n (SEQ ID NO: 2) at its C-terminal end, in which n is 1 to 5; and in which each X is a naturally occurring amino acid residue that is independently chosen.
9. Method according to claim 2, wherein each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
10. Method according to claim 4, wherein each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
The capturing and/or detection agent having 1-5 amino acid residues that are linked to the exposed C-terminal end of the ISV with sequence VTVSS of the co-pending claims correspond to the modified ISV of the instant claims. This capturing and/or detection agent has been modified in the issued claims as required by the instant claims. Issued claim 1 meets the limitations of instant claims 50 and 54. The limitations of instant claims 52-53 are present in issued claims 2-4 and 9-10.
The claims are not patentably distinct.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(4) Claims 50 and 52-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-8 of U.S. Patent No. 10,323,090 (applicant Merck Sharp & Dohme Corp.; inventors Bowman, Beaumont, Buyse, Boutton, Dombrecht, Vlerick, and Kastelein) in view of Merchiers et al. (WO 2008/101985, of record ). The ’090 patent has inventors Buyse, Boutton, and Dombrecht in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01.
Issued claim 6 is directed to a multispecific binder with a C-terminal extender. Claim 7 depends upon claim 6 and shows that the C-terminal end (without the C-terminal extender) can be VTVSS for LAG3, a therapeutic target. Claim 8 specifically recites that the C-terminal extender is an alanine (i.e. the C-terminal end of the multispecific binder is VTVSSA). The VTVSSA C-terminal ending for LAG3 meets the ISVD limitations of claims 50 and 52-55. Claim 9 depends upon claim 6 and is directed to a multispecific binder having a human serum albumin (HSA) ISVD of SEQ ID NO: 142 (ending in VTVSS) at the C-terminal end with a C-terminal extender of alanine (i.e. the C-terminal end of the multispecific binder is VTVSSA). The VTVSSA C-terminal ending for HSA meets the ISVD limitations of claims 50, 52-54, and 56. The issued claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by claim 50 is the modification step. The issued claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the ‘090 multispecific binders.
The claimed methods are not patentably distinct from the issued claims in view of Merchiers et al.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(5) Claims 50 and 52-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7, and 11 of U.S. Patent No. 10,501,542 (applicant Merck Sharp & Dohme Corp.; inventors Punnonen, Beaumont, Buyse, Boutton, Dombrecht, Victor, and Kastelein) in view of Merchiers et al. (WO 2008/101985, of record ). The’542 patent has inventors Buyse, Boutton, and Dombrecht in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01.
Issued claim 1 is directed to a CTLA4 binder with half-life extender and/or a C-terminal extender. Issued claims 3-5 indicate that the half-life extender can be an albumin binding ISVD of SEQ ID NO: 66 (ending in VTVSS). Issued claim 6 indicates that the C-terminal extender can be alanine. Issued claim 11 is an example of the CTLA4 binder of claim 1 ending in an ISVD that binds serum albumin and has a C-terminal extender of alanine. SEQ ID NO: 62 ends in VTVSSA. Human serum albumin is a therapeutic target within the meaning of the claims.
The VTVSSA C-terminal ending for the CTLA4 binders of the issued claims meet the ISVD limitations of claims 50 and 52-56. The issued claims are directed to products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by claim 50 is the modification step. The issued claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the ‘542 multispecific binders.
The claimed methods are not patentably distinct from the issued claims in view of Merchiers et al.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(6) Claims 50 and 52-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 11-12, and 14-15 of U.S. Patent No. 11,168,135 (applicant Merck Sharp & Dohme Corp; inventors Bowman, Beaumont, Buyse, Boutton, Dombrecht, Kastelein, and Vlerick). The ‘135 patent has inventors Buyse, Boutton, and Dombrecht, in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01. Although the claims at issue are not identical, they are not patentably distinct from each other.
Issued claim 4 is directed to a method of recombinantly producing a PD1 binder having a half-life extender and a C-terminal extender. Issued claim 11 provides PD1 binding ISVDs that end in VTVSS. Issued claim 12 indicates that the C-terminal extender is alanine. Issued claims 14-15 indicate that the half-life extender can be an ISVD that binds albumin and ends in VTVSS.
Human serum albumin is a therapeutic target within the meaning of the claims.
The VTVSSA C-terminal ending for the PD1 binder of the issued claims meets the ISVD limitations of claims 50 and 52-56.
The only step required by claim 50 is the modification step. This is met by the method of the ‘135 claims.
The issued claims disclose what to make and how to perform the modification using recombinant techniques meeting the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the ‘135 purified PD1 binders.
The claims are not patentably distinct.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(7) Claims 50 and 52-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5-6 and 8-9 of U.S. Patent No. 11,649,290 (applicant Merck Sharp & Dohme Corp.; inventors Punnonen, Beaumont, Buyse, Boutton, Dombrecht, Victor, and Kastelein) in view of Merchiers et al. (WO 2008/101985, of record ). The ‘290 patent has inventors Buyse, Boutton, and Dombrecht in common with the instant application. It does not share common priority. There is no prohibition against double patenting. See MPEP 804.01.
Issued claims 5-6 are directed to CTLA4 binders with half-life extender and a C-terminal extender of alanine. Issued claims 8-9 are examples of the CTLA4 binders of claims 5-6 ending in an ISVD that binds serum albumin and has a C-terminal extender of alanine. SEQ ID NOS: 62 and 64 end in VTVSSA. Human serum albumin is a therapeutic target within the meaning of the claims.
The VTVSSA C-terminal ending for the CTLA4 binders of the issued claims meet the ISVD limitations of claims 50 and 52-56. The issued claims are directed to products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by claim 50 is the modification step. The issued claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the ‘290 multispecific binders.
The claimed methods are not patentably distinct from the issued claims in view of Merchiers et al.
Applicant has acknowledged this rejection and traverses. Applicant’s arguments are addressed below.
(8) Claims 50 and 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 12,516,105.
This rejection corresponds to the double patenting rejection set forth in the prior Office action over claims 44 and 48 of copending Application No. 17/408,987 (6/5/2025 claim set) (applicants Ablynx NV and Sanofi; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer). Application No. 17/408,987 issued as U.S. Patent No. 12,516,105 on 6 January 2026. This is not a new ground of rejection.
The issued patent and the instant application have a common priority claim. They are both continuations of parent application 14/128,681 and have the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1 and 4 from patent ‘105 are reproduced below.
1. A method comprising: (i) introducing one or more amino acid substitutions or additions in the C-terminal region of an immunoglobulin single variable domain (ISV), or a protein or a polypeptide comprising the ISV at its C-terminus, to generate a modified ISV, protein, or polypeptide, wherein the C-terminal region comprises Kabat positions 11, 13, 14, 15, 82, 82a, 82b, 83, 84, 107, 108, 109, 110, 111, 112, and 113; and (ii) performing an immunoassay comprising the steps of: contacting the modified ISV, protein or polypeptide with a biological sample comprising antibodies or with an antibody obtained from the biological sample, wherein the biological sample is from a subject that has never received an ISV; and detecting any antibody bound to the modified ISV, protein or polypeptide.
4. The method of claim 1, wherein the ISV is a VHH, a humanized VHH, a VH, or a camelized VH.
The only step required by instant claim 50 is modifying the ISV, protein, or polypeptide by adding 1 to 10 amino acid residues to its C-terminal end, each amino acid independently chosen from any amino acid to generate a modified ISV.
Issued claim 1 fairly suggests adding at least one amino acid following Kabat position 113, a recited position in the C-terminal region. As such, the methods of the ‘105 patent meet the limitations of the instant claims. Issued claim 4 meets the limitations of instant claim 54. It is noted that Kabat positions 109-113 are VTVSS in an unmutated VHH ISVD.
The claims are not patentably distinct.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
(9) Claims 50 and 52-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-35 of U.S. Patent No. 11,192,938 (applicant Ablynx NV; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer) in view of Merchiers et al. (WO 2008/101985, of record). This patent and the instant application have a common priority claim. They are both continuations of parent application 14/128,681 and have the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01.
The C-terminal endings of the issued claims meet the ISVD limitations of instant claims 50 and 52-53. The issued claims meet the limitations of instant claim 54. Issued claim 22 recites an ISV binding a therapeutic target meeting the limitations of instant claims 55. The issued claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by instant claim 50 is the modification step. The issued claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the claimed ISVD polypeptides.
The claimed methods are not patentably distinct from the issued claims in view of Merchiers et al.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
(10) Claims 50 and 52-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,006,352 (applicant Ablynx NV; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer) in view of Merchiers et al. (WO 2008/101985, of record). This patent and the instant application have a common priority claim. They are both continuations of parent application 14/128,681 and have the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01.
The C-terminal endings of the issued claims meet the ISVD limitations of instant claims 50 and 52-53. The issued claims meet the limitations of instant claim 54. Issued claim 1 recites
a serum albumin binding ISV meeting the limitations of instant claims 55-56. Serum albumin is a therapeutic target within the meaning of the claims. The issued claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by instant claim 50 is the modification step. The issued claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the claimed ISVD polypeptides.
The claimed methods are not patentably distinct from the issued claims in view of Merchiers et al.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
(11) Claims 50 and 52-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 61, 63-67, and 69-71 of copending Application No. 14/128,681 (1/22/2025 claim set) (applicants Ablynx NV and Sanofi; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer) in view of Merchiers et al. (WO 2008/101985, of record). This application and the instant application have a common priority claim. The instant application is a continuation of parent application 14/128,681 and has the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01.
The C-terminal endings of the co-pending claims meet the ISVD limitations of instant claims 50 and 52-53. The co-pending claims meet the limitations of instant claim 54. Co-pending claim 48 recites an ISV that binds a therapeutic target meeting the limitation of instant claim 55. The co-pending claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by instant claim 50 is the modification step. The co-pending claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the claimed ISVD polypeptides.
The claimed methods are not patentably distinct from the co-pending claims in view of Merchiers et al.
This is a provisional nonstatutory double patenting rejection. It is noted that the co-pending claims were allowed on 14 January 2026.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
(12) Claims 50 and 52-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51 and 54-56 of copending Application No. 17/409,019 (2/13/2025 claim set) (applicants Ablynx NV and Sanofi; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer) in view of Merchiers et al. (WO 2008/101985, of record). This application and the instant application have a common priority claim. They are both continuations of parent application 14/128,681 and have the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01.
The C-terminal endings of the co-pending claims meet the ISVD limitations of instant claims 50 and 52-53. The co-pending claims meet the limitations of instant claim 54. The co-pending claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by instant claim 50 is the modification step. The co-pending claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the claimed ISVD polypeptides.
The claimed methods are not patentably distinct from the co-pending claims in view of Merchiers et al.
This is a provisional nonstatutory double patenting rejection.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
It is noted that double patenting rejections in co-pending application 17/409,019 similar to those of the instant application were appealed to the Patent Trial and Appeal Board. These rejections were affirmed in the decision dated 21 November 2025. Appellant appealed this decision to the United States Court of Appeal for the Federal Circuit on 12 January 2026.
(13) Claims 50 and 52-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 13-20, and 24-30 of copending Application No. 18/299,871 (2/7/2025 claim set) (applicants Ablynx NV and Sanofi; inventors Baumeister, Bouche, Boutton, Buyse, Snoeck, Staelens, Dombrecht, Schotte, Ververken, Beste, Hermans, Steffensen, Szyroki, and Denayer) in view of Merchiers et al. (WO 2008/101985, of record). This application and the instant application have a common priority claim. They are both continuations of parent application 14/128,681 and have the same patent term filing date. There is no prohibition against double patenting. See MPEP 804.01.
The C-terminal ending alanine (A) of the co-pending claims meet the ISVD limitations of instant claims 50 and 52-53. The co-pending claims meet the limitations of instant claim 54. Co-pending claim 13 recites that the ISVD binds a therapeutically relevant target meeting the limitation of instant claim 55. The co-pending claims are directed products and not methods.
Merchiers et al. discloses well-known recombinant techniques for recombinantly producing multivalent ISVD constructs. See at least pages 90-95.
The only step required by claim 50 is the modification step. The co-pending claims disclose what to make and Merchiers et al. documents that those of ordinary skill in the art would have known how to perform the modification using recombinant techniques resulting in a method having the steps of the instant claims. Reduced aspecific binding to the C-terminal end would be an inherent property of the claimed ISVD polypeptides.
The claimed methods are not patentably distinct from the co-pending claims in view of Merchiers et al.
This is a provisional nonstatutory double patenting rejection.
Applicant has acknowledged this rejection and will consider filing a terminal disclaimer.
It is noted that double patenting rejections in co-pending application 18/299,871 similar to those of the instant application were appealed to the Patent Trial and Appeal Board. There has been no decision on this appeal.
With respect to the double patenting rejections of (1)-(7), applicant argues that the double patenting rejections set forth as (1)-(7) should be withdrawn for various reasons.
Applicant’s arguments are acknowledged but are not agreed with. These arguments are not persuasive for the reasons of record set forth in the Office action dated 23 September 2025.
Applicant continues to assert that “the material facts of the instant case are the same as those at issue in Ex parte Baurin et al., in which the Board held that the asserted references were not proper nonstatutory double patenting (NSDP) References and overturned the asserted NSDP rejections in view of these references.”
Applicant asserts that “On December 18, 2025, the P.T.A.B. issued a Decision on Request for Rehearing with respect to Ex parte Baurin et al. in which the P.T.A.B. denied the Request for Rehearing by Examiner. See Ex parte Baurin et al., Decision on Request for Rehearing, pages 23-24,” and describes how “The PTAB reaffirmed that the asserted references were not proper NSDP References and that the asserted NSDP rejections were improper.”
The decision set forth in the “DECISION ON REQUEST FOR REHEARING” in 17/135,529 (the application of Baurin et al. which was considered in Ex Parte Baurin et al.) was not a precedential opinion. Finally, an order convening an appeals review panel and granting a sua sponte rehearing of the Board's Decision on Appeal and Decision on Request for Rehearing in 17/135,529 was granted on 5 March 2026.
It is again noted that double patenting rejections in co-pending application 17/409,019 similar to those of the instant application were appealed to the Patent Trial and Appeal Board. These rejections were affirmed in the decision dated 21 November 2025. Appellant appealed this decision to the United States Court of Appeal for the Federal Circuit on 12 January 2026.
It is maintained that the double patenting rejections are proper and in accordance with MPEP 804.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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