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
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/20/2026 has been entered.
Status of the Claims
2. Claims 1-85 are the original claims filed for this application on 11/15/2021. In the Preliminary Amendment of 2/4/2022, Claims 34, 36, 54, 63, 69, and 74 are amended, Claims 1-32, 35, 37-47, 52, 55-62, 64-68, 70, 73, and 75-85 are canceled, and new Claims 86-92 are added. In the Reply of 5/24/2024, new Claims 93-96 are added. In the Response of 10/22/2024, Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86, and 95 are amended and Claims 34, 91 and 93-94 are canceled. Applicants state in the Response that Claims 91 and 93-94 are canceled however as evident from the claim set, claim 34 is canceled. In the Response of 4/14/2025, claims33, 53-5474 and 86 are amended, claims 89-90, 92, and 95-96 are canceled, and new claim 97 is added. In the Response of 8/21/2025, Claims 33, 53-54, 63, and 69 are amended, Claim 97 is canceled, and new Claim 98 is added. In the RCE of 1/20/2026, Claims 33, 36, 48, 53, 86, and 88 are amended, and new Claims 99-102 are added.
Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86-88 and 98-102 are the pending claims.
This Office Action contains new grounds for objection and rejection.
Priority
3. USAN 17/454,938, filed 11/15/2021, and having 2 RCE-type filing therein, is a Continuation of 15/228,616, filed 08/04/2016, now U.S. Patent # 11254744 and having 4 RCE-type filing therein, 15/228,616 Claims Priority from Provisional Application 62/202,665, filed 08/07/2015.
Information Disclosure Statement
4. As of 6/15/2026, a total of six (6) IDS are filed for this application: 2/4/2022; 5/24/2024; 10/22/2024; 4/14/2025; 8/21/2025; and 1/20/2026. The corresponding initialed and dated 1449 form is considered and of record.
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Written Description
5. The rejection of Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86-88 and 98-102 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 is maintained. New claims 99-102 are joined under this outstanding rejection.
A) Applicants allege Table 3 of Example 4, non-limiting embodiments of the claimed amino acid sequence of an engineered or artificial hinge region in an antibody or an antibody fragment (Claim 33), or of the hinge region within the claimed antibody or antibody fragment (Claim 53). The length of the hinge regions in Table 3 (including the upper, core and lower hinge regions) ranges from 27 amino acids (γ1 EH3) to 32 amino acids (γ3/γ1 EH8).
Response to Arguments
Applicants have not identified support for the phrase “at least one of SEQ ID NO:259 or SEQ ID NO: 260” (claim 33) and “at least one of SEQ ID NO:261 or SEQ ID NO: 262” (claim 53).
1) Even assuming, arguendo, the phrase is supported by working embodiments, the POSA could reasonably conclude that the phrase “the artificial hinge region is 24-32 amino acids long” is inaccurate based on the description of what comprises the elements for an artificial hinge in the newly amended claim 33.
Claim 33 “artificial hinge region” comprises: at least one of the amino acid sequence (or two amino acid sequences); and a lower hinge region C-terminal to the at least one amino acid sequence.
Two sequences of SEQ ID NO:259 or two sequence SEQ ID NO 260, would comprise 26 and 28 amino acids in length, respectively. One of each sequence of SEQ ID NO:259 and SEQ ID NO 260 would comprise 29 amino acids in length.
The specification teaches examples of the length in amino acids for lower hinge regions at
[0009] In some aspects, an amino acid hinge region for an antibody is provided, it can comprise an upper hinge region that comprises no amino acids capable of crosslinking with a corresponding amino acid; and a core hinge region connected to a C-terminus of the upper hinge region, wherein the core hinge region comprises at least three cysteines per strand. In some aspects, the amino acid hinge region further comprises a lower hinge or extension region connected C-terminal to the core hinge region, wherein the lower hinge or extension sequence is at least one of: APPVAGP (SEQ ID NO: 60), APELLGGP (SEQ ID NO: 58), and/or GGGSSGGGSG (SEQ ID NO: 59). In some aspects, the upper hinge region comprises no cysteines that crosslink within the upper hinge region. In some aspects, the upper hinge region comprises no cysteines. In some aspects, it further comprises a lower hinge or extension region. In some aspects, the lower hinge or extension region comprises at least one of: GGGSSGGGSG (SEQ ID NO: 59) or APPVAGP (SEQ ID NO: 60) or APELLGGP (SEQ ID NO: 58).
[0255] In some embodiments, the extension or lower hinge region comprises at least one of S, G, A, P, or V. In some embodiments, the extension sequence comprises at least GGGSSGGGSG (SEQ ID NO: 59). In some embodiments, the extension or lower hinge region comprises at least APPVAGP (SEQ ID NO: 60). In some embodiments, the lower hinge region comprises at least one of: GGGSSGGGSG (SEQ ID NO: 59) or APPVAGP (SEQ ID NO: 60). In some embodiments, the lower hinge sequence can be a GS linker, extension sequence, and/or any native lower hinge region from γ1, γ2, γ3 and γ4.
Addition of the lower hinge sequence GGGSSGGGSG (10 amino acids) to two sequences of SEQ ID NO:259 or two sequence SEQ ID NO 260, would comprise 36 and 38 amino acids in length, respectively. Addition of the lower hinge sequence GGGSSGGGSG (10 amino acids) to one of each sequence of SEQ ID NO:259 and SEQ ID NO 260 would comprise 39 amino acids in length. The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
Addition of the lower hinge sequence APPVAGP (7 amino acids) to two sequences of SEQ ID NO:259 or two sequences SEQ ID NO 260, would comprise 33 and 35 amino acids in length, respectively. Addition of the lower hinge sequence APPVAGP (7 amino acids) to one of each sequence of SEQ ID NO:259 and SEQ ID NO 260 would comprise 36 amino acids in length. The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
Addition of the lower hinge sequence APELLGGP (8 amino acids) to two sequences of SEQ ID NO:259 or two sequences SEQ ID NO 260, would comprise 34 and 36 amino acids in length, respectively. Addition of the lower hinge sequence APELLGGP (8 amino acids) to one of each sequence of SEQ ID NO:259 and SEQ ID NO 260 would comprise 37 amino acids in length. The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
2) Even assuming, arguendo, the phrase is supported by working embodiments, the POSA could reasonably conclude that the phrase “the artificial hinge region is 24-32 amino acids long” is inaccurate based on the description of what comprises the elements for an artificial hinge in the newly amended claim 53.
Claim 53 “artificial hinge region” comprises: at least one of the amino acid sequence (or two amino acid sequences); an upper hinge region; a core hinge region C-terminal to the upper hinge region; and a lower hinge region.
For an abbreviated analysis, an upper hinge region is not defined in any of the claims that depend from claim 53. The specification teaches upper hinge regions at Table 1. Claim 53 defines the core hinge region is CPPCPPC (SEQ ID NO: 52). A lower hinge region is defined in claim 54.
Addition of the lower hinge sequence GGGSSGGGSG (10 amino acids) and a core hinge CPPCPPC (7 amino acids) to two sequences of SEQ ID NO:261 or two sequence SEQ ID NO 262, would comprise 42 and 45 amino acids in length, respectively (and this calculation does not include the upper hinge). Addition of the lower hinge sequence GGGSSGGGSG (10 amino acids) and a core hinge CPPCPPC (7 amino acids) to one of each sequence of SEQ ID NO:261 and SEQ ID NO 252 would comprise 46 amino acids in length (and this calculation does not include the upper hinge). The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
Addition of the lower hinge sequence APPVAGP (7 amino acids) and a core hinge CPPCPPC (7 amino acids) to two sequences of SEQ ID NO:261 or two sequence SEQ ID NO 262, would comprise 40 and 42 amino acids in length, respectively (and this calculation does not include the upper hinge). Addition of the lower hinge sequence APPVAGP (7 amino acids) and a core hinge CPPCPPC (7 amino acids) to one of each sequence of SEQ ID NO:261 and SEQ ID NO 252 would comprise 43 amino acids in length (and this calculation does not include the upper hinge). The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
Addition of the lower hinge sequence APELLGGP (8 amino acids) and a core hinge CPPCPPC (7 amino acids) to two sequences of SEQ ID NO:261 or two sequence SEQ ID NO 262, would comprise 41 and 43 amino acids in length, respectively (and this calculation does not include the upper hinge). Addition of the lower hinge sequence APELLGGP (8 amino acids) and a core hinge CPPCPPC (7 amino acids) to one of each sequence of SEQ ID NO:261 and SEQ ID NO 252 would comprise 44 amino acids in length (and this calculation does not include the upper hinge). The POSA could reasonably conclude that the meaning of an “artificial hinge region is 24-32 amino acids long” and based on foregoing analysis, is incorrect.
The rejection is maintained based on Applicants amendment of the 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 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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
6. The rejection of Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86-88 and 98 on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11254744 is maintained.
Applicants request that the rejection is held in abeyance is granted. The response is incomplete and the rejection is maintained.
7. The rejection of Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86-88 and
Applicants provide a schematic that allegedly disposes of the arguments of record that the extension sequence of ref claim 2 “cannot be more than 10 amino acids between the extension sequence and the C-terminus of the polypeptide chain, and that a CH3 domain is longer than 10 amino acids.”
Response to Arguments
Ref claim 2
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The polypeptide chain of an antigen binding construct defined by ref claim 2 comprises either (i) a VH or (ii) a VH/VL (e.g., a scfv) and the extension sequence located at or within 10 amino acids of the C-terminus of the polypeptide. Ref claim 2 recites that the polypeptide is then covalently connected to “a different polypeptide chain” thru disulfide bonds by way of the extension. The ref specification teaches throughout that a meaningful antigen binding construct is a minibody that comprises the extension feature:
The term “antibody” includes scFv and minibodies. Thus, each and every embodiment provided herein in regard to “antibodies” is also envisioned as scFv and/or minibody embodiments.
Other antigen-binding fragments or antibody portions of the invention include, bispecific scFv antibodies where the antibody molecule recognizes two different epitopes, single binding domains (sdAb or nanobodies), and minibodies.
Studies showed that insertion of a repeating “PPC” (Pro-Pro-Cys) motif into a hinge of a human IgG1 based minibody molecule results in stabilization of minibody dimers and proper disulfide pairing.
A minibody is well understood in the art to mean a scfv-CH3 domain:
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The rejection is maintained.
New Grounds for Objection
Claim Objections
8. Claims 33, 36, 48-51, 53-54, 63, 69, 71-72, 74, 86-88 and 98-102 are objected to because of the following informalities:
a) Amend claim 33 to reduce excess verbiage and to reflect generic claim 53, lines 8-9. Replace the first “wherein” paragraph of claim 33
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to recite: “wherein Xn1, Xn2, Xn3, Xn7, Xn8, and Xn9 are each any naturally occurring amino acid except cysteine, and wherein Xn10 is P or E.”
Dependent claims 36, 48-51, 63, 69, 71-72, 74, 98-99 and 101 fall under the objection.
b) Amend claim 53 to replace “or antibody fragment” with “or antibody fragment thereof.” See [0023, 0166, 0182] in the specification.
Dependent claims 54, 86-88, 100 and 102 fall under the objection.
c) Amend claim 86 to recite “…after the administering step.”
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claims 49-51 and 98 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 49-51 and 98 are drawn to “the hinge region” that in depending from Claim 33 is a broadening recitation. Claim 33 recites “a lower hinge region” and is currently amended to recite “an artificial hinge region”. Claims 49-51 and 98 are unclear as to whether/which hinge of claim 33 is referenced.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
10. No claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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