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
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 6, 9-16, 20, 23-24, 27, 32-38, and 41 and species: antibody or antigen-binding fragment, a human antibody, SEQ ID NOs: 105-107 and 118-120, a solid cancer, a lung cancer, and intravenous in the reply filed 04/23/2026 is acknowledged.
Claims 33, 39-40 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 04/23/2026.
Claims 1-3, 6, 9-16, 20, 23-24, 27, 32, 34-38, and 41 are now under consideration in the instant Office Action.
Claim Rejections - 35 USC § 112
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 6, 9-10, and 12-13 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.
Instant claim 6 recite sequences for the heavy and light chain variable region CDRs in groupings of three by the heavy chain variable region CDRs and the light chain variable region CDRs, joined by an “and/or”. As recited, the claims can be interpreted as either claiming the antibody by only 3 of the 6 necessary CDRs, or as being able to mix and match any grouping of three CDRs with another to construct the entire antibody. This results in an unclear description of what CDRs construct an embodiment of the antibody. Applicant is encouraged to amend the claims to recite the antibodies in groups of three heavy and three light chain CDRs joined by “and”, and to separate the various antibody embodiments by “or” to construct the three distinct antibodies recited in the instant claim. Dependent claims 9-10 and 12-13 are included in this rejection because they fail to remedy the issue of the claim from which they depend.
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 1-3, 9-10, 12-13, 15-16, 20, 23-24, 27, 32-38, 41 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
See MPEP §2163(I)(A) which states: "The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
Claim 1 calls for an HHLA2 binding agent with a functional requirement of inhibiting HHLA2 binding to KIR3DL3 and enhancing HHLA2 binding to TMIGD2. There is no specific structural requirement for the HHLA2 binding agent beyond the required function. Further, instant claim 15 requires that the agent is capable of binding to the same epitope on HHLA2 and/or competes for binding without providing a structure for the claimed agent. Claim 35 calls for the HHLA2 binding agent to be used in combination with a second agent, but fails to describe the identity of what the components of the combination are. The required function of the HHLA2 binding agent can be achieved in any form, no specific structure is required, as long as they bind to KIR3DL3 and enhance HHLA2 binding to TMIGD2. The scope of the claim is so broad and reads on so many possible genera that it is clear that the specification fails to describe all of the possible means of achieving the response linked to its function. The claims do not require any agent or that they possess any particular conserved structure or other disclosed distinguishing features. Therefore, the genera are merely defined by function and the instant specification fails to describe the full genera of the possible methods that are encompassed by these claims.
There is no structural requirement for the claimed HHLA2 binding agents beyond function. The binding agent of claims 2-3 do not even have a defined structure for the antibody species it recites; the claimed activity of the agents can be achieved in any form as long as the agents provide the specifically claimed function. Further, compounded by the limitation of variants of the HHLA2 binding agent is unclear what would meet the requirements for binding to KIR3DL3 and enhancing HHLA2 binding to TMIGD2
There are a few specific examples of HHLA2 binding agents in the instant specification, but there is no support provided that the applicants have envisioned all of the possible variants encompasses by these functional requirements of the instant claims. Further, the instant claims do not require that the claimed agents possess any particular conserved structure or other disclosed distinguishing feature. The scope of the terms of the “HHLA2 binding agent” is so broad and reads on so many possible genera and the instant specification fails to describe any of the possible trafficking or targeting agents that are encompassed by this term. The “agent” encompasses any agent that has the required function but the instant specification fails to teach all the possible agents encompassed by the possible agents in the instant claim. The claims do not require that the “agent” possess any particular conserved structure or other disclosed distinguishing feature. The term “agent” encompasses many things including antibodies or antigen-binding fragments, small molecules, polypeptides, aptamers, or proteins as long as they achieve the required function. Additionally, instant claim 15 requires a competitive agent that is an antibody that competes for binding with the same epitope on HHLA2 as the HHLA2 binding agent of claim 1 without reciting any particular structure for the competitive agent. Thus the claims are drawn to multiple genera of molecules that are defined only by they function as immunosuppressive agent. Therefore, the genus is merely defined by function and the instant specification fails to describe the full genus of molecules that are encompassed by this claim.
To provide adequate written description and evidence of possession of claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of prospective activity or function. There is not even identification of any particular portion of the structure that must be conserved for said activity except its function. The specification does not provide a complete structure of all possible forms of the claims agents and variants and fails to provide a representative number of species for any genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genera of HHLA2 binding agent variants with a functional requirement of binding to KIR3DL3 and enhancing HHLA2 binding to TMIGD2.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed structure of the encompassed agents, fragments and variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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 1-3, 15-16, 20, 23-24, 27, 32, 34-38, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Dana-Farber Cancer Institute (WO 2019/204057 A1, in IDS filed 02/29/2024, hereinafter “DFCI”), in view of Albert Einstein College of Medicine (US 2019/0263886 A1, in IDS filed 02/29/2024, hereinafter “AECM”).
DFCI teaches an HHLA2 binding agent capable of: (i) inhibiting HHLA2 binding to KIR3DL3 using an anti-HHLA2 antibody and (ii) selectively inhibiting the interaction between HHLA2 and its binding inhibitor receptor, KIR3DL3, without blocking or significantly inhibiting the interaction between HHLA2 and its binding stimulatory receptor, TMIGD2, see claims 47 and 49, and Figure 22. This meets the limitations of instant claim wherein 1 wherein an HHLA2 binding agent is capable of inhibiting HHLA2 binding to KIR3DL3 and enhancing HHLA2 binding to TMIGD2, instant claim 15 wherein an agent binds and/or competes for binding on HHLA2.
DFCI also teaches that the HHLA2 binding agent is or comprises an antibody or antigen-binding fragment thereof, a small molecule, a polypeptide, or an aptamer and that the “the antibody or antigen-binding fragment thereof is or comprises: (i) a chimeric antibody, 3 human antibody. or a humanized antibody. or antigen-binding fragment thereof: (ii) a monospecific antibody or a bispecific antibody, or antigen-binding fragment thereof; and/or (iii) a monoclonal antibody, or antigen-binding fragment thereof”, see Abstract. This meets the limitations of instant claims 2 and 3 wherein the HHLA2 binding agent is an antibody or antigen-binding fragment thereof, a small molecule, a polypeptide, or an aptamer. DFCI also teaches that the monoclonal antibody, or antigen-binding fragment thereof, is administered in a pharmaceutically acceptable formulation, see reference’s claim 34. This meets the limitations of instant claim 23 wherein the binding agent is comprised within a pharmaceutical formulation.
DFCI teaches “a method of treating a subject afflicted with cancer comprising administering to the subject at least one monoclonal antibody, or antigen-binding fragment thereof”, see reference’s claim 30. The cancers that may be treated by this method include lung cancer, see reference’s claim 38. This meets the limitations of instant claim 24 wherein the HHLA2 binding agent is a monoclonal antibody that modulates immune function to treat cancer and instant claim 27 wherein the cancer is a lung cancer. DFCI also teaches that the disease is associated with aberrant HHLA2 expression, see reference’s claims 18 and 20. This meets the limitations of instant claim 32 wherein the disease is associated with aberrant HHLA2 expression.
DFCI teaches the intravenous administration of the binding agent, see page 148. This meets the limitations of instant claim 34 wherein the binding agent is administered intravenously. DFCI teaches that the “therapeutic agents of the present invention can be used alone or can be administered in combination therapy with, e.g., chemotherapeutic agents, hormones, anti-angiogens, radio-labelled, compounds, or with surgery, cryotherapy, and/or radiotherapy”, see page 148. This meets the limitations of instant claim 35 wherein the HHLA2 binding agent is administered in combination with a second agent.
DFCI discloses that “a host cell which comprises the isolated nucleic acid described herein, comprises the vector described herein, expresses the antibody, or antigen-binding fragment thereof, described herein” and “a device or kit comprising at least one monoclonal antibody, or antigen-binding fragment thereof, described herein, the device or kit optionally comprising a label to detect the at least one monoclonal antibody, or antigen-binding fragment thereof, or a complex comprising the monoclonal antibody, or antigen-binding fragment thereof” is provided, see reference’s claim 14. This meets the limitations of instant claim 36 wherein a nucleic acid encodes the HHLA2 binding agent, instant claim 37 wherein an expression vector comprises the nucleic acid, instant claim 38 wherein a host cell comprises the expression vector, and instant claim 41 wherein the HHLA2 binding agent is a monoclonal antibody comprised within a kit.
Instant claims 16 and 20 are drawn to inherent functions of the HHLA2 binding agent dependent upon structure. Since the instant claims do not require a particular structure, one of ordinary skill in the art would recognize that the binding agent taught by DFCI would have the same binding activity as claimed as they implicate the same pathways.
However, DFCI does not teach that the HHLA2 binding agent enhances HHLA2 binding to TMIGD2. AECM remedies this deficiency.
AECM teaches a binding agent comprising TMIGD2 extracellular domain which binds to HHLA2 strongly. and can enhance anti-tumor immunity, see paragraphs 0049 and 0052 respectively wherein “their ability to bind to HHLA2 was tested. It was also found that a fusion protein of Transmembrane and Immunoglobulin Domain Containing (2) (TMIGD2, FIG. 1A), the extracellular domain of TMIGD2 linked to the Fc region of human IgG1 (TMIGD2-1g), bound strongly to 3T3 cells overexpressing HHLA2" and "TMIGD2 protein and its derivatives can bind cancer- expressed HHLA2 and therefore enhance anti-tumor immunity by blocking HHLA2-mediated immunosuppression”. This meets the limitations of instant claims 1 wherein the HHLA2 binding agent enhances binding to TMIGD2.
It would be obvious at the time of the instant invention to use the anti-HHLA2 binding agent that is a monoclonal antibody taught by DFCI, which is a binding agent that results in the inhibition of binding to KIR3DL3, with the HHLA2 binding agent taught by AECM which teaches that binding of TMIGD2 with HHLA2 can enhance anti-tumor immunity. One would be motivated to combine the teachings of DFCI and AECM with the expectation of creating an optimized binding agent in the form of a monoclonal antibody which has enhanced binding of HHLA2 to TMIGD2 while inhibiting HHLA2 binding to KIR3DL3, to achieve a desired treatment efficiency in treating cancers by modulating immune system activity, using routine experimentation.
Therefore, claims 1-3, 15-16, 20, 23-24, 27, 32, 34-38, and 41 are rejected as obvious over DFCI and AECM.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. 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.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights