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 .
Information Disclosure Statement
The information disclosure statements (IDS) filed 11/18/2023 and 12/27/2024 have been considered and the references therein are of record.
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.
Claim 12 is 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.
Claim 12 is indefinite for reciting “a second antibody or antigen binding fragment thereof of claim 1, wherein said antibody is bispecific” because there is insufficient antecedent basis for this limitation. Claim 1 does not recite a second, bispecific antibody and therefore the “second antibody” recited in claim 12 is unclear.
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 2, 4, 6-9, and 20-21 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. The claims recite human antibody (claim 2), amino acid sequences having 80-99% identity to SEQ ID NOs: 7-10, and methods of using the antibody to treat any cancer (claim 20), each of which encompasses a genus of agents. These claims do not require that the genera possess any particular structure or other distinguishing feature that is characteristic of the genera as a whole. Therefore the claims are drawn to a genera for which there is inadequate written description.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C).
Regarding the genera encompassed by the claims, the specification describes species in the working Examples that fall within the claimed genera (Specification pg. 37-45). From the specification, it is clear that Applicant is in possession of the species of a humanized anti-PD1 antibody or antigen binding fragment thereof with 100% identity to SEQ ID NOs: 1-10 capable of treating a mouse model of colon carcinoma, CT26. The claims, however, are not limited to those species but also includes the genera of a human antibody, amino acid sequences having 80-99% identity to SEQ ID NOs: 7-10, and the antibody capable of treating any cancer. The applicant provides no evidence for possession of a human antibody or a method of treating any cancer. In regards to claims 4 and 6-9, the specification does not provide a representative number of species for the immensely broad genera of any sequence that has 80-99% identity to SEQ ID NOs: 7-10. In regard to claims 20-21, Zio et al., 2025 (see PTO-892) teaches that glioblastoma is often refractory to anti-PD1 therapies (see abstract & conclusion), and Sun et al., 2020 (see PTO-892) teaches that there is varied success in using anti-PD1 therapies in the treatment of cancer, including non-small cell lung cancer, colorectal cancer, urothelial carcinoma, and melanoma (see Table 1 & conclusion). The specification provides no evidence that the claimed antibody is able to treat all cancers or melanoma. Moreover, the specification fails to provide a representative number of species within the recited genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of each genus as a whole, or representative number of species within each genus, the specification does not provide adequate written description of the claimed genera.
Claims 20-21 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 an anti-PD1 antibody or antigen binding fragment thereof with CRDs 1-6, as outlined in claim 1, capable of treating colon carcinoma, does not reasonably provide enablement for the genus of 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 make and use the invention commensurate in scope with these claims.
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, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed composition is that it covers the use of the claimed antibody to treat any cancer, including lymphoma, melanoma, colorectal adenocarcinoma, prostate cancer, breast cancer, colon cancer, lung cancer, liver cancer, gastric cancer, and renal clear cell carcinoma. As the breath of the claims encompass a wide scope of compositions, a skilled artisan would not know how to make the composition with a reasonable expectation of success based solely on what is disclosed in the specification.
The amount of direction provided by the inventor and the level of predictability in the art:
The specification does not provide direction as to methods of using the antibody to treat any cancer. The art teaches that not all cancers can be treated with anti-PD1 therapies: Zio et al., 2025 (see PTO-892) teaches that glioblastoma is often refractory to anti-PD1 therapies (see abstract & conclusion) and Sun et al., 2020 (see PTO-892) teaches that there is varied success in using anti-PD1 therapies in the treatment of multiple cancers, including non-small cell lung cancer, colorectal cancer, urothelial carcinoma, and melanoma (see Table 1 & conclusion). The art at the time of filing does not provide enabling guidance and the specification as filed does not provide guidance that overcomes this unpredictability within the art.
The existence of working examples:
What is enabled by the working examples is narrow in comparison to the breadth of the claims: the specification discloses use of the antibody to treat colon carcinoma, but does not provide working examples for the genera recited above.
The quantity of experimentation needed to make or use the invention:
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc., V. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that: "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all of the disclosure related to the process is within the skill of the art","[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling for the full scope of the claimed invention because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Given that the nature of the invention is treating all cancers, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials, or in animal models that are predictive of treatment, in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to make and use the method with a reasonable expectation of success.
Therefore, claims 20-21 lack enablement.
Relevant Art
The prior art does not reasonably suggest an antibody that binds to an extracellular domain of PD-1 with the complementary determining region (CDR region) of the heavy chain variable region in the antibody comprising CDR1H shown in SEQ ID NO: 1, the CDR2H as shown in SEQ ID NO: 2, and the CDR3H as shown in SEQ ID NO: 3, and with the CRD region of the light chain variable region comprising CDR1L shown in SEQ ID NO: 4, the CDR2L as shown in SEQ ID NO: 5, and the CDR3L as shown in SEQ ID NO: 6.
The closest prior art is EUGENIO et al., 2003 (US20030157090A1), Tipton et al., 2017 (US20170044259A1), Nguyen et al., 2018 (US20180141998A1), Bennett et al., 2018 (US20180179285A1), Peritt et al., 2003 (US20030157105A1), and Dylla et al., 2013(US20130302355A1).
Eugenio teaches an anti-Her2 nanobody having the sequence set forth in SEQ ID NO: 9 (Db) that has 100% sequence identity to instant SEQ ID NO: 1 (Qy), as shown below.
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181
640
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Tipton teaches an anti-PD1 antibody having the sequence set forth in SEQ ID NO: 1786 (Db) that has 89.8% sequence identity to instant SEQ ID NO: 2 (Qy), as shown below.
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170
660
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Nguyen teaches a cancer neoepitope having the sequence set forth in SEQ ID NO: 1159329 (Db) that has 80.4% sequence identity to instant SEQ ID NO: 3 (Qy), as shown below.
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158
679
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Bennett teaches an antibody having the sequence set forth in SEQ ID NO: 134 (Db) that has 100% sequence identity to instant SEQ ID NO: 4 (Qy), as shown below.
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167
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Peritt teaches an anti-p40 Ig derived protein having the sequence set forth in SEQ ID NO: 5 (Db) that has 100% sequence identity to instant SEQ ID NO: 5 (Qy), as shown below.
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176
646
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Dylla teaches an anti-CD46 antibody having the sequence set forth in SEQ ID NO: 177 (Db) that has 100% sequence identity to instant SEQ ID NO: 6 (Qy), as shown below.
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170
662
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The prior art does not reasonably suggest combining all six CRDs with 100% sequence identity to SEQ ID NO: 1-6 into one antibody. Therefore, instant claim 1 is allowable as the prior art does not reasonably suggest an isolated antibody or antigen binding fragment thereof, comprising a HC variable region sequence and a LC variable region sequence, wherein the antibody binds to an extracellular domain of PD-1 with a binding affinity better than 10 nM as determined by SPR analysis, and where the HC comprises CDRs with sequence identity as set forth in SEQ ID NOs: 1-3 and the LC comprises CDRs with sequence identity as set forth in SEQ ID NOs: 4-6.
Conclusion
Claim 2, 4, 6-9, 12, and 20-21 are rejected. Claims 1, 3, 10-11, 13-16, and 18-19 are allowable.
Advisory Information
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/JOSEPH D. CESARE/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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