DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election of group I, claims 1-3, 5-7, 11, 13, 15-17, in the reply filed on 2/24/26 is acknowledged. Applicant has elected VH2/VL2 as the species of antibody. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Upon reconsideration, the restriction requirement between groups 1 and 3 is withdrawn and claim 12 is being included in the examination.
Claims 1-3, 5-7, 11-13, and 15-17 are being acted upon.
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 1-2, 5-7, 11-13, 15-17 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.
The scope of the claimed CDRs encompassed in claim 1 is unclear and indefinite. The instant specification on page 3 discloses that CDR sequences can be determined using Kabat, Chothia, Kabat+chotia, AbM, IMGT or contact numbering schemes. In other words, the specification discloses exemplary numbering schemes. The instant specification also discloses on pages 11-12 that general rules may be used to define the CDRs in an antibody. In Table 1 it is also noted that some of the numbering schemes can vary depending on the individual publication examined. Thus, the specification does not define the metes and bounds of the CDRs encompassed by the present claims, and it is unclear what specific CDRs sequences are encompassed by the present claims. As taught by Dondelinger, different numbering conventions and CDR definitions exist, which is confusing and can lead to aberrant CDR identification. Dondelinger also teaches that defining CDRs based on amino acid sequence can be complicated with some systems using sequence alignments and others using 3D architecture. Thus, in the absence of a limiting definition, it is not clear what precise amino acid residues from the VH and VL of SEQ ID NO: 3 and 5 would be required as CDRs. For example, would be claims encompass CDRs numbering schemes such as Gelfand, Honnegers, and other bioinformatical tools like paratome? The specification discloses numbering via Kabat+Chothia, which would appear to encompass mixing and matching different CDR definitions. Would the claims encompass VH CDRs from Kabat with VL CDRs from Chothia? Would the claims encompass using IMGT+Kabat numbering? The scope of the claims is unclear and indefinite. Amendment to recite particular CDR SEQ ID NOs:, as in claim 3, would be remedial.
Claim 5 is indefinite in that it recites that the arginase 1 binder comprises an antibody or antigen biding fragment “VH2” comprising SQ ID NO: 2 and a “VL2” comprising SEQ ID NO: 5. The way the claim is worded implies that the antibody is “VH2”, however VH2 is an variable heavy chain domain and not an antibody. Are the claims intending to limit the arginase binders to an antibody or antibody fragment thereof, or is the limitation of antibody or antigen fragment thereof in reference only the “VH2” portion of the claim. Amendment to recite, for example, that the Arginase 1 binder is an antibody or antigen binding fragment thereof that comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 3 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 5, would be remedial.
Claim 6 is unclear since it is directed to the arginase 1 binder of claim 1, wherein “the antibody” further comprises a heavy chain constant domain. There is insufficient antecedent basis for this term, since claim 1 is directed to an arginase 1 binder comprising CDRs of an antibody VH or an antibody VL. It is unclear whether “the antibody” is meant to refer to “an antibody VH” and/or “an antibody VL” in claim 1, or whether claim 6 is meant to limit the scope of the arginase 1 binders to an antibody further comprising said heavy chain constant regions.. If the former, it is noted that claim 6 would fail to further limit the scope of claim 1, since claim 6 would be directed to an arginase 1 binder of claim 1, having CDRs of the antibody VH of SEQ ID NO: 3 further comprising a constant domain (i.e. the same CDRs already required in claim 1). A similar issue exists for claim 7, which depends from claim 6. The scope of the claim is unclear and indefinite.
Claim 17 recites that “the antibody” is an anti-PD1 antibody. It depends from claims 1 and 16. Claim 1 recites that the binder has CDRs of “an antibody” and claim 16 recites that the therapeutic agent is “a therapeutic antibody”. The use of “the antibody” in claim 17 is indefinite because it unclear which antibody is being referred to, i.e. is it referring to “an antibody” from claim 1, or “a therapeutic antibody” from claim 16. Amendment to claim 17 to recite “the therapeutic antibody” would be remedial.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 12 and 15-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating cancer comprising administering to an individual in need thereof an Arginase 1 binder of claim1, or a combination therapy for treating cancer comprising an Arginase 1 binder of claim 1;
does not reasonably provide enablement for:
A method of treating a proliferative disease comprising administering to an individual in need thereof an Arginase 1 binder of claim1, or a combination therapy for treating a proliferative disease comprising an Arginase 1 binder of claim 1;
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The instant claims are directed to compositions and method of treating cancer or any “proliferative disease” with the Arginase binder of claim 1. This encompasses treating a wide range of diseases with different etiologies and pathological mechanisms, which would be highly unpredictable given the current state of the art. For example, “proliferative diseases” would encompass treating autoimmune disease, which are characterized by aberrant proliferative response in the immune system. The state of the art is such that the role of arginase 1 in the genus of diseases is highly complex and unpredictable. Arginase 1 catalyzes hydrolysis of the amino acid L-arginine, thereby depleting extracellular arginine (see Steggerda, 2017, of record). T cells require L-arginine for proliferation, and blocking Arginase 1 activity in the context of cancer favors T cell proliferation, alleviates immunosuppression, and treat cancers (see Steggerda, 2017 and Cane, 2023). However, in the context of autoimmune disease, increasing T cell proliferation can be detrimental. For example, see Khoshnejad, 2020, which teaches that Arginase activity is immunosuppressive and increasing Arginase activity can treat inflammatory (i.e. proliferative) autoimmune conditions. Thus, treating any proliferative disease with an Arginase 1 antibody, that the instant specification discloses as blocking Arginase activity, would be highly unpredictable.
Thus, given the unpredictability of the art, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims. The instant specification disclose the antibody of claim 1 inhibits arginase 1 activity. The specification does not provide any guidance regarding treating proliferative diseases, as broadly claimed, which encompass autoimmune diseases. Given the unpredictability of the art, the lack of guidance provided by the instant specification, and the breadth of the claims, it would require undue experimentation to practice the full scope of the claimed method.
No claim is allowed. Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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