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
Claims 1-9, 11, 15 and 19-20 are pending in the application and are under examination.
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 1-3, 8-9, 11, 15 and 19-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
The teachings of the specification and the claimed invention:
The nature and scope of the claimed invention at issue is a genus of VEGFA binding comprising single domain antibodies that comprise CDR sequences as set forth in the claims which can vary in up to 11 positions (see e.g., claim 1), nucleic acids encoding the single domain antibody and methods of treating or preventing VEGFA diseases.
The specification discloses in the examples isolating single domain antibody clones that bind VEGFA from libraries where one clone is designated 16C2.1 and another is designated 21A5.1. These clones have the following VH sequences and CDR sequences given on page 38 and which are claimed in claims 4-7:
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However, the specification does not disclose that variations of these CDR which retain binding to VEGF. Notably, as evidenced by these sequences the CDR sequences differ greatly in amino acid sequence, respectively.
State of the Art
It is established in the art that single domain antibodies comprise 3 CDRs involved in antigen binding and these CDRs are variable regions that differ in sequence and are selected to bind an antigen (see Muyldermans et al (ARB:82:775-797, 2013, entire document, e.g., 777-780). There is no evidence in the art or the specification that single residues or combinations of residues can be altered as set forth in the instant claims and retain binding.
The teachings from Muyldermans et al highlight that a skill artisan cannot recognize or predict that a CDR from one single domain antibody can be altered and retain binding.
Claim Analysis
The instant claims encompass a subgenus of single domain antibodies that bind to VEGFA which comprise CDR sequences as set forth in the claims which can vary in up to 11 positions.
A skilled artisan would recognize that the specificity of a single domain antibody is dependent upon its three specific CDR sequences. The instant specification discloses 2 clones that are sufficient for antigen-binding specificity to VEGFA, but does not identify that other CDR combinations encompassed by the claims retain binding to VEGFA. Notably, the claims encompass thousands of antibodies which have not been determined to bind VEGFA.
As discussed above, single domain antibodies comprise 3 CDRs involved in antigen binding and these CDRs are variable regions, but one cannot envision which other sets of CDRs encompassed by the claims will bind to VEGFA. It is noted that, “[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added). In this case, a skilled artisan cannot visualize CDRs in a single domain antibody that binds to VEGFA other than the sets of 3 CDRs from the two clones.
Then with respect to preventing VEGFA diseases in general such as cancer or preventing or treating ALS, it is noted that Applicant has not established that any of the claimed antibodies would have the function of preventing cancer or treating or preventing amyotrophic lateral sclerosis (ALS). Notably, preventing cancer 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. Then with respect to treating and preventing ALS it is noted that the specification discloses that antibody 16C2.1 and 21A5.1 block VEGFA and VEGFR1 interaction by binding VEGFA (see pages 49-50). However, Pronto-Laborinho et al (BioMed Res. Int., Article 947513, 1-24, 2014) discloses that overexpressing VEGFA in neurons partially rescued a mouse model of ALS, delaying motor neuron loss, the onset of weakness and increasing survival (see page 10). Accordingly, it does not appear that antibodies that block VEGFA function would treat all VEGFA diseases or treat or prevent ALS.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
Claims 19 and 20 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for using methods such as treating VEGFA mediated cancers comprising administering to a subject an effective amount of an antibody of claim 4 or 6 does not reasonably provide enablement for using the full scope of the claimed methods such as preventing or treating all VEGFA mediated diseases such as preventing cancer or treating or preventing ALS . 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 or treating all VEGFA mediated diseases, it is noted that the art of Pronto-Laborinho et al (BioMed Res. Int., Article 947513, 1-24, 2014) discloses that overexpressing VEGFA in neurons partially rescued a mouse model of ALS, delaying motor neuron loss, the onset of weakness and increasing survival (see page 10). Accordingly, it does not appear that antibodies that block VEGFA function would treat all VEGFA diseases or treat or prevent ALS.
Therefore, one of skill in the art would be subject to undue experimentation to determine how to treat and prevent any and all VEGFA mediated diseases, because VEGFA mediated diseases include diseases where it is unlikely the claimed agent would be effective.
Furthermore, with respect to preventing VEGFA mediated diseases such as cancer, 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 VEGFA mediated diseases, would not reasonably enable the artisan to prevent such diseases without undue and/or unreasonable experimentation.
Here, there is no disclosure of testing using any model to determine if any of the claimed antibodies as claimed can prevent VEGFA mediated diseases in any mammal; again, the assertion that the invention is useful is based solely upon merely prophetic examples.
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.
Conclusion
No claims are allowed. Claim 4-7 are objected to for depending upon rejected claim 1.
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 Mon-Fri.
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.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
January 28, 2026