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 .
Claims 1-15 are pending and currently under consideration.
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.
Claims 2-5 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.
Among other variable heavy and light chains, Claim 1 recites a VL1 CDR comprising SEQ ID NO:40 in which SEQ ID NO:40 comprises: SSTGAVTSGNYPNG. This sequence is also present in applicant’s submitted sequence listing of 04-15-2024.
Dependent claims 2-5 do not further limit claim 5 because they do not comprise SEQ ID NO:40. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
For example, claim 2 states:
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However, neither of SEQ IDs: 120 and 121 comprise SEQ ID NO:40. For example, SEQ ID NO:120 is present below with the reference to SEQ ID NO:40 underlined. It would appear that the issue relates to the last amino acid residue (G) of SEQ ID NO: 40.
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The same is true for Claims 3 and 5 as none of the claimed sequences incorporate or comprise the amino acid sequence of Claim 40. 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.
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 12-13 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 methods of treating cancer, does not reasonably provide enablement for methods of treating any and all diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The focus of the enablement inquiry is whether everything within the scope of the claim(s) is/are enabled, at the time of filing, without requiring undue experimentation to make or use the invention. The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) or 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. The claims are drawn to a method of treating a disease in a subject comprising administering the activatable bispecific polypeptide complex of claim 1 to the subject wherein the subject is a human. The broadest reasonable interpretation of claims 12-13 encompasses the treatment of any disease in a human subject comprising administering the bispecific polypeptide complex of claim 1. For example, the specification teaches [0066] that “treatment” or “therapy” of a subject refers to any type of intervention or process performed on, or the administration of an active agent to, the subject with the objective of reversing, alleviating, ameliorating, inhibiting, slowing down progression, development, severity or recurrence of a symptom, complication or condition, or biochemical indicia associated with a disease.
The state of the prior art and the level of predictability in the art: The specification teaches [0007] that the administered polypeptide encompasses an activatable anti-EGFR, anti-CD3 heteromultimeric bispecific polypeptide complex (HBPC). Similar state of the art complexes teach that the epidermal growth factor receptor (EGFR) is an attractive target for the immunotherapy of EGFR+ tumors while the anti-CD3 portion is used to redirect cytokine-induced killer cells (CIK) to the tumor cells. For example, Ma et al. (Oncology Reports, 34: 2567-2575, 2015) assessed the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for
its ability to redirect CIK cells to target EGFR-positive glioblastoma (See Figure 3A). Compared with the unarmed control CIK cells, EGFRBi-armed CIK cells inhibited tumor growth in vivo. (Page 2573, bottom of page and Figure 6A-6B). Further, Boustany et al. (Boustany, Leila M., et al. "Abstract A164: EGFR-CD3 bispecific Probody™ therapeutic induces tumor regressions and increases maximum tolerated dose> 60-fold in preclinical studies." Molecular Cancer Therapeutics 17.1_Supplement (2018): A164-A164.) teach a T cell-engaging Bispecific Probody therapeutic (Pb-TCB) targeting Epidermal Growth Factor Receptor (EGFR) and CD3 optimized for affinity, effector function, masking, and cleavability. In established tumor models the authors demonstrated that Pb-TCBs potently induce tumor regressions. However, other than cancer, there does not appear to be any other specific diseases that are predictably treated with similar anti-CD3/anti-EGFR constructs.
The amount of direction provided by the inventor and the existence of working examples: The specification teaches [0171] non-limiting examples of disease include: cancers, rheumatoid arthritis, Crohn's disease, SLE, cardiovascular damage, ischemia, etc. For example, indications can include leukemias, including T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic diseases including multiple myeloma, and solid tumors, including lung, colorectal, prostate, pancreatic and breast, including triple negative breast cancer. Working examples however are limited to the inhibition of tumor cell growth; see for example paragraphs 0247-0248. The instant specification does not provide any in vitro or in vivo data demonstrating that the bispecific complex would predictably treat any other diseases such as cardiovascular damage or ischemia. Therefore, the specification does not provide sufficient guidance or direction to enable the treatment of any and all diseases.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004)). One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to treating any and all diseases, and applicant has not shown that bispecific complexes targeting CD3 and EGFR would predictably treat a wide variety of diseases. Further, as set forth above, the state of the art does not appear to teach the treatment of other diseases with bispecific complexes targeting CD3 and EGFR. For example, a search of bispecific, CD3 and EGFR and Parkinson’s revealed no established literature for anti-CD3/EGFR for treatment of Parkinson’s Disease. A similar search for treating cystic fibrosis did not reveal any literature establishing a biological mechanism or therapeutic indication linking anti-CD3 and anti-EGFR with cystic fibrosis. Hence, to one of ordinary skill in the art, it would not be predictable nor could one reasonably expect that treating any and all diseases, except cancer, would be accomplished by the claimed method. The specification provides insufficient guidance with regard to these issues and provides no working examples commensurate to the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth, and it cannot be predicted from either the disclosure or the state of the art that all diseases would be treated with the claimed heterodimeric complex. Therefore, undue experimentation would be required to enable the claims as written.
Claim Objections
Claims 1 and 3 are objected to because of the following informalities:
Claim 1 states:
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The examiner believes the claims should be drawn to “wherein VL1 and VL[H]3 each comprise” as the accompanied sequences are variable light chains.
Claim 1 further states:
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The VL CDR3 is missing a sequence identifier.
Claim 3 is drawn to:
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It would appear that reference to the “second” polypeptide (underlined above) should instead reference the fourth polypeptide.
Appropriate corrections are requested.
Claims 6-11 and 14-15 are also objected to because they ultimately depend from Claim 1 and claim 1 is not allowable.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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