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
The amendment filed March 6, 2024, is acknowledged and has been entered. Claims 4, 6-7, 20- 21, 23, 39, 47, 62, 66, 71, 74, 76, 79, and 81 have been amended. Claims 3, 5, 8-17, 19, 22, 24-38, 40-46, 48-61, 63-65, 67-70, 72-73, 75, 77-78, 80, and 82-91 have been cancelled. Claims 92 and 93 have been added.
Claims 1, 2, 4, 6-7, 18, 20-21, 23, 39, 47, 62, 66, 71, 74, 76, 79, 81 and 92-93 are pending and under examination.
Information Disclosure Statement
The information disclosure statement has been considered.
Objections
The specification and claims 4 and 21 are objected to for failing to comply with the sequence requirements. Sequences appearing in the claims are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for sequences must appear in the text of the claims, even if the sequence is also embedded in the text of the claims of the patent application. See claim 4 which recites multiple SEQ ID NO: X and claim 21 and the specification at ¶ 39 and other paragrpah which recites sequences such as GGGGS and others without a SEQ ID NO:. Due to the multiple sequence compliance issues, Applicant should review the entire application to ensure there are no other deficiencies in complying with the sequence requirements.
Applicant Must Provide:
An initial or substitute computer readable form (CRF) copy of the “Sequence Listing”.
An initial or substitute paper copy of the “Sequence Listing”, as an amendment specifically directing its entry into the application.
A statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R.1.821(e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.8
Claim 7 is objected to for reciting “e. said sdAb bins”.
Claim 62 is objected to for reciting “cancer or in a subject”.
Claim Rejections - 35 USC § 112
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 62 and 66 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for using methods such as treating cancer by the claimed method does not reasonably provide enablement for using the full scope of the claimed methods such as preventing cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors, which have been outlined in the Federal Circuit decision of In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), include, but are not limited to, the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed. See also Ex parte Forman, 230 USPQ 546 (BPAI 1986).
The amount of guidance, direction, and exemplification disclosed in the specification, as filed, would not be sufficient to enable the skilled artisan to make and/or use the claimed invention at the time the application was filed without undue and/or unreasonable experimentation.
With respect to preventing all cancers, it is noted that preventing hyperproliferative disorders, including cancers and tumors, i.e., keeping individuals free of any such disorders indefinitely, is an intractable proposition, if not now wholly impossible, given, for example, that cancers are widely heterogeneous diseases, having widely varying pathologies and etiologies, and with causes that are multifactorial and as yet only partially characterized and poorly understood. It is generally recognized that a disease cannot be prevented unless and until its causes are fully appreciated and understood to a degree that it becomes possible to intercede effectively to block its onset or development by any cause. Notably, in this case, the specification presents merely prophetic examples that the recited compositions would be effective to prevent cancers. As such, the specification, which lacks any specific non-general guidance, direction, and exemplification that is reasonably commensurate in scope with the intended use of preventing cancer, would not reasonably enable the artisan to prevent such diseases without undue and/or unreasonable experimentation.
Furthermore, there is no disclosure of testing using any model to determine if any of the claimed methods as claimed can prevent cancers in any mammal or prevent all cancers; again, the assertion that the invention is useful is based solely upon merely prophetic examples. Notably, the specification presents evidence in Example 6 that a mouse model treating with a dimeric VHH of the invention in combination with a PD-1 antibody killed tumor cells administered to the mouse, but this does not establish that a dimeric VHH construct of the invention is able to prevent all cancers.
Accordingly, the specification, which lacks any specific non-general guidance, direction, and exemplification that is reasonably commensurate in scope with the intended use of preventing cancer, would not reasonably enable the artisan to prevent cancer without undue and/or unreasonable experimentation because one would need to determine how to use the claimed methods to prevent. Obviously, such experimentation would be considered undue and/or unreasonable because decades of research has been carried out to identify viable treatments that prevent cancer, and that research continues to this day.
Applicant is reminded that reasonable correlation must exist between the scope of the claims and scope of enablement set forth.
In deciding In re Fisher, 166 USPQ 18, 24 (CCPA 1970), the Court indicated the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. “Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC 1997).
In conclusion, upon careful consideration of the factors used to determine whether undue experimentation is required, in accordance with the Federal Circuit decision of In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988), the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enable the skilled artisan to make and/or use the claimed invention at the time the application was filed without undue and/or unreasonable experimentation.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 18 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by WO 2021/155071 A1, IDS (Timmer et al).
The term “membranal CD28” is not expressly defined in the instant specification, so the scope of the claimed single domain antibodies is being interpreted as antibodies that bind to CD28 on the surface of a cell, such as those that bind the extracellular domain (ECD) of CD28).
Timmer et al discloses a dimeric agent comprising at least two membranal CD28 binding single domain antibodies (sdAbs) (the scAbs bind the ECD of CD28), wherein a first binding sdAb is linked to a second binding sdAb by a linker (see entire document, e.g., pages 96-98, 108 and 293-294 and claims).
Accordingly, Timmer et al anticipates the claim absent a showing otherwise.
Claims 18 and 81 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by WO 2019/175885 A1, IDS (Hakim et al).
The term “membranal CD28” is not expressly defined in the instant specification, so the scope of the claimed single domain antibodies is being interpreted as antibodies that bind to CD28 on the surface of a cell, such as those that bind the extracellular domain (ECD) of CD28).
With respect to claim 18, Hakim et al discloses a dimeric agent comprising at least two membranal CD28 binding single domain antibodies (sdAbs) (sdABs or VHHs that bind the ECD of CD28), wherein a first binding sdAb is linked to a second binding sdAb by a linker (see entire document, e.g., pages 20-22, 33 and 59).
With respect to claim 81, Hakim et al discloses that after these agents are obtained and linked testing an ability of the agent to block cleavage of mCD28 by a protease, and selecting at least one agent that blocks cleavage of mCD28 by the protease (see pages 55-56).
Accordingly, Hakim et al anticipates the claims absent a showing otherwise.
Conclusion
Claims 1-2, 6, 20, 23, 39, 47, 71, 74, 76, 79 and 92-93 are allowed. The closest prior art is WO 2020/183473 A1, IDS which discloses antibodies 2A1, 4A4 and 4A1 (see page 65) and antibody 2A1 was used as the starting sequence for affinity maturation methods that altered CDRs of the parental antibody (see instant specification, Example 1 on pages 91-92), such that each antibody claimed in claim 1 is not taught in the prior art. While affinity maturation methods were known in the art, the instant CDR sequences could not be predicted based on the CDR sequences of antibody 2A1 alone, such that the instant antibodies also are not obvious over the disclosures on the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571)272-9935. The examiner can normally be reached on M-F.
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 on (571)272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
July 24, 2026
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