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 .
Status of the Claims
Claims 235 – 250 were pending. Claims 240 – 246, and 249 have been amended; claims 235 – 239, 247 – 248, and 250 have been canceled; and claims 251 – 262 have been newly added. Claims 240 – 246, 249, and 251 – 262 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/15/2026 follows the provisions of 37 CFR 1.97 and has been considered by the examiner.
REJECTIONS WITHDRAWN
Claim Rejections - 35 USC § 103
Claims 235 – 250 were rejected under 35 U.S.C. 103 as being unpatentable over UNDERWOOD (WO 2015/184099 A1, published 12/03/2015; see PTO-892: Notice of References Cited of 11/19/2024) in view of FAUSTMAN (WO 2020/102739 A1, published 05/22/2020; see PTO-892 of 11/19/2024).
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Double Patenting
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 15 of U.S. Patent No. 10,906,982 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of U.S. Patent No. 11,859,002 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 22 of U.S. Patent No. 9,821,010 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 – 2, 26, 29, 32, 36, 84, 87, 185 – 188, 219, 374, and 377 – 380 of copending Application No. 17/294,008 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 258 and 260 – 323 of copending U.S. Application No. 17/269,315 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 134 – 136, 138 – 144, 147 of copending U.S. Application No. 17/561,448 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of copending U.S. Application No. 17/924,455 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of copending U.S. Application No. 18/540,207 in view of UNDERWOOD, FAUSTMAN and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of copending U.S. Application No. 18/928,513 in view of UNDERWOOD, FAUSTMAN, and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 – 2, 26, 29, 32, 36, 84, 87, 185 – 188, 219, 374, and 130 – 131, 188, and 190 – 198 of copending Application No. 17/150,686 in view of UNDERWOOD, FAUSTMAN, and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
Claims 235 – 239 and 246 – 250 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 194 – 203 of copending Application No. 18/399,071 in view of UNDERWOOD, FAUSTMAN, and SILVA.
In view of the claim amendments in the reply of 06/15/2026, this rejection is withdrawn.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
Claim Rejections - 35 USC § 112
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.
Claims 256 – 261 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Scope of Enablement
Claims 256 – 261 are rejected under 35 U.S.C. 112(a) because the present claims recite a method of treating a human subject to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection comprising administering to the human subject the antibody or antigen-binding fragment of claim 240 or of claim 245. However, neither the specification nor the prior teaches the steps of the claimed methods that would enable one skilled in the art to use the antibody or antigen-binding fragment of claim 240 or 245.
In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ 2d 1400 (Fed. Cir., 1988) as to undue experimentation. The factors include:
1) the nature of the invention;2) the scope or breadth of the claims;3) the state of the prior art;4) the predictability or unpredictability of the art; 5) the relative skill of those skilled in the art; 6) the presence or absence of working examples; 7) the amount of direction or guidance presented and,8) the quantity of experimentation necessary.
The relevant factors are addressed below in the assessment of undue experimentation.
Scope or breadth of the claims and the nature of the invention: Present claim 256 and dependent claims thereon recite: a method of treating a human subject to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection comprising administering to the human subject the antibody or antigen-binding fragment of claim 240.
Present claim 260 and dependent claims thereon recite a method of treating a human subject to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection comprising administering to the human subject the antibody or antigen-binding fragment of claim 245.
State of the prior art and degree of predictability or unpredictability in the art: Although the prior art teaches the correlation between TNFR2 and inflammation, the correlation is convoluted. For example, CHEN (Chen Y, et al. (2023) Therapeutic potential of TNFR2 agonists: a mechanistic perspective. Front. Immunol. 14:1209188; see PTO-892: Notice of References Cited) teaches that TNFR2 agonists have been investigated as potential therapies for inflammatory diseases. However, the role of TNFR2 signaling in coordinating immune or inflammatory responses under different pathological conditions is complex. See CHEN at the abstract. CHEN teaches that “[a]lthough several TNFR2 agonistic antibodies were demonstrated in the clinical trial, how the TNFR2 agonistic antibody elicits a different immune response in vivo remains largely unknown. Identifying the factors that affect biological consequences induced by TNFR2 agonists may pave the way to the more effective treatment of cancer or autoimmune diseases.” See CHEN at p. 7, last sentence under Conclusion and future perspective. Thus, the pathology involving TNFR2 is not fully understood in the prior art.
Furthermore, the prior art does not cover the full scope of an immune response, an autoimmune disease, an inflammatory disease, an allergy, or a transplant rejection in a method of treating a human subject.
Relative skill possessed by those in the art: In view of the state and complexity of the prior art, and the scope of the claims, which are drawn to a method of treating a human subject to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection comprising administering to the human subject the antibody or antigen-binding fragment of claim 240 (claim 256) or of claim 245 (claim 260), the level of skill in the art is high and is at least that of a medical doctor or Ph.D. scientist with several years of experience in the field of medicine.
Presence or absence of working examples: The present specification provides prophetic and generic examples of administration of a TNFRSF antibody to a patient suffering from an autoimmune or inflammatory disease or a cancer or infectious disease (Examples 5 – 7, p. 203 – 206). The specification does not provide specific steps with specific doses and regimens in methods of treating specific diseases.
Amount of guidance or direction provided/Quantity of experimentation required: The specification only provides guidance regarding the effects of anti-human TNFR2 agonist on human T cells (specification at Example 3, p. 197 – 201) and does not include any direction on how administer to the human subject the antibody or antigen-binding fragment of claim 240 or 245 in a method of treating a human subject to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection.
In the absence of working examples, undue experimentation would be necessary to determine the scope of “to modulate an immune response, treat an autoimmune disease, treat an inflammatory disease, treat an allergy, or treat a transplant rejection comprising administering to the human subject” of present claims 256 – 260.
Conclusion: In summary, the claims contain subject matter which is not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 242 – 243 and 245 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 242 – 243 and 245 depend from claim 240 either directly or indirectly. Claim 240 requires the heavy chain variable region to comprise an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1488 and the light chain variable region to comprise an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1495. However, claims 242 – 243 and 245 recite sequences (SEQ ID NOs: 1501 and 1508) for the heavy chain variable region and the light chain variable region that are different than that of SEQ ID NOs: 1488 and 1495, respectively, for the antibody of claim 240. Thus, it is not clear how the heavy chain variable region and the light chain variable region each requires two different sequences.
Allowable Subject Matter
Claims 240 – 241, 244, 246, 249, 251 – 255, and 262 are allowed.
Th cited references of record teach TNFR2 agonists and their function in the immune response. For example, FAUSTMAN (WO 2020/102739 A1; published 02/22/2020; see PTO-892 of 11/19/2024) is directed to agonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to stimulate the proliferation of regulatory T cells (Treg cells) and/or myeloid-derived suppressor cells (MDSCs), as well as to inhibit the function of, reduce the proliferation of, and/or directly kill, T effector cells, such as CD8+ T effector cells. FAUSTMAN teaches that the TNFR2 polypeptides can be used, for example, to suppress autoimmunity and inflammation, as well as to promote the protection, healing, preservation, and/or regeneration of a wide variety of tissues and organs, such as tissues and organs containing TNFR2+ cells. See FAUSTMAN at the abstract. However, FAUSTMAN does not teach TNFR2 antibodies having the claimed sequences of present independent claims 240 and 262. Thus, claims 240 and 262 and non-rejected claims dependent on claims 240 and 262 are free of the art.
Conclusion
Claims 242 – 243, 245, and 256 – 261 are rejected. Claims 240 – 241, 244, 246, 249, 251 – 255, and 262 are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights