DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .2. This action is in response to the amendment filed on 10 June 2026. Applicant's arguments and amendments to the claims have been fully considered but do not place the application in condition for allowance. All objections and rejections not reiterated herein are hereby withdrawn.
The species of the DDR2 copy number has been rejoined with the elected species of the SDHC copy number and the species of a bicycle tumor targeted immune agonist specific for Nectin-4 has been rejoined with the elected species of a bicycle toxin conjugate specific for Nectin-4.
Claim Status
3. Claims 51-72 are pending.
Claim 72 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 51-71 have been examined herein.
Maintained / Modified Claim Rejections - 35 USC § 112(b) - Indefiniteness
4. 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 53 and 63 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.
Claims 53 and 63 are indefinite over the recitation of “SDHC Log2 copy number ratio” because this phrase is not defined in the claims and there does not appear to be a limiting definition for this phrase in the specification. It is acknowledged that the specification (para [0110]) states “As used herein, the term “an SDHC amplification” refers to an increase in SDHC DNA copy number over normal tissue. In some embodiments, this is expressed as Log 2 of the copy number ratio or SDHC Log 2(CN ratio).” In view of the language “in some embodiments,” and because the claim does not recite “SDHC amplification,” it is unclear as to whether the copy number ratio is with respect to that of SDHC in a normal tissue from the subject, or from any other subject or to some other unspecified copy number.Response to Remarks:
The response states:
“As an initial matter, the term "Log2 (CN ratio)" refers to the base 2 logarithm of the copy number ratio [of SDHC]. The term "copy number ratio" refers to the ratio of the copy number of a target gene (e.g. SDHC) to the copy number of a reference gene (e.g. CEN1, a gene located within the centromere of chromosome 1). The skilled person would understand what is meant by this term in the context of tumor gene amplifications. For example, this term is used without further explanation in Riester et al. cited by the examiner. Nevertheless, without wishing to appear to agree with the Examiner, and in the interest of expediting prosecution, claims 53 and 63 have been
amended to recite "Log2 copy number ratio," thus rendering the rejection moot.”
These arguments have been fully considered but are not persuasive. The claims do not specify the denominator in the copy number ratio. Neither the specification nor the claims recite that the SDHC copy number ratio is the ratio of the copy number of SDHC to the copy number of the reference / normal control gene of CEN1. While the phrase may be used in the prior art, including the reference of Riester, this does not render the present claims definite since the present claims require that the patient has a particular SDHC Log2 copy number ratio but the claims do not define the denominator in the ratio. Thereby, the metes and bounds of the claimed subject matter is not clear.
Maintained Claim Rejections - 35 USC § 112 first paragraph – Written Description
5. 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 51-71 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.
In analyzing the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note that with regard to genus/species situations, a “Satisfactory disclosure of a “representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed.”
The claims are drawn to methods that require administering a bicycle toxin conjugate specific for Nectin-4 to a subject selected as having a SDHC copy number of more than two in a tumor. With respect to the rejoined subject matter, the claims also include methods that require administering a bicycle tumor targeted immune agonist specific for Nectin-4 to a subject selected as having a SDHC copy number of more than two in a tumor.
The claims do not define the bicycle toxin conjugate specific for Nectin-4 or bicycle tumor targeted immune agonist specific for Nectin-4 in terms of their complete structure or in terms of any other relevant structural properties.
Note that while claims 56 and 66 recite that the bicycle toxin conjugate specific for Nectin-4 is BT8009, these claims are not limited to methods wherein the agent administer to the patient is a bicycle toxin conjugate specific for Nectin-4. Similarly, while claims 57, 59, 66 and 69 recite that the bicycle tumor targeted immune agonist specific for Nectin-4 is BT7480, these claims are not limited to methods wherein the agent administer to the patient is a bicycle tumor targeted immune agonist specific for Nectin-4.
The claims encompass methods that require administering a potentially large genus of structurally undefined compounds for the treatment of a subject having a tumor.
The specification teaches only the bicycle toxin conjugate specific for Nectin-4 of BT8009 set forth on p. 17 of the specification.
The specification (para [0069-0070]) states:
“As used herein, the term “a Bicycle toxin conjugate specific for Nectin-4” refers to a Bicycle toxin conjugate that binds specifically to Nectin-4. Various Bicycle toxin conjugates specific for Nectin-4 have been described previously, for example, in US 2019/03889906, WO 2019/243832, and WO 2019/243833, the content of each of which is incorporated herein by reference in its entirety. BT8009 is referred to as BCY8245 in US 2019/03889906, WO 2019/243832, and WO 2019/243833.
The term “BT8009,” as used herein, is a Bicycle toxin conjugate having a structure as shown below, or a pharmaceutically acceptable salt thereof, wherein the molecular scaffold is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA), and the peptide ligand comprises the amino acid sequence:
(β-Ala)-Sar10-CiP[1Nal][dD]CiiM[HArg]DWSTP[HyP]WCiii(SEQ ID NO: 1)
wherein Sar is sarcosine, 1Nal represents 1-naphthylalanine, HArg represents homoarginine, HyP represents hydroxyproline and Ci, Cii and Ciii represent first, second and third cysteine residues.”
The cited applications disclose a limited number of bicycle toxin conjugates specific for nectin-4 in addition to BT8009/BCY8245. Each of the bicycle toxin conjugates specific for nectin-4 that are disclosed in the cited applications appear to have the same peptide ligand region of present SEQ ID NO: 1.
Similarly, regarding the bicycle tumor targeted immune agonist specific for Nectin-4, the specification (para [0073]) states:
“the term “Bicycle tumor targeted immune agonists (TICAs) specific for Nectin-4” refers to Bicycle tumor targeted immune agonists (TICAs) that bind specifically to Nectin-4. Various Bicycle tumor targeted immune agonists (TICAs) specific for Nectin-4 have been described previously, for example, in US 2019/0307836, WO 2019/193328, US 2021/0040154, WO 2021/019244, and WO 2021/019246, the content of each of which is incorporated herein by reference in its entirety. BT7480 is referred to as BCY11863 in US 2021/0040154, WO 2021/019244, and WO 2021/019246. The term “BT7480” is a Bicycle tumor targeted immune agonist (TICA), which is heterotandem bicyclic peptide complex consisting of a Nectin-4 specific peptide linked to two CD137 specific peptides via a N-(acid-PEG3)-N-bis(PEG3-azide) linker, having a structure as shown below.”
The cited applications disclosed appear to teach BT7480, also known as BCY11863, and a heterotandem bicyclic peptide complex comprising a first peptide ligand consisting of SEQ ID NO: 1 therein and a second peptide ligand having the sequence of SEQ ID NO: 2 therein.
The bicycle toxin conjugates specific for nectin-4 and bicycle tumor targeted immune agonist specific for nectin-4 disclosed in the present application and in the cited applications do not constitute a representative number of the conjugates encompassed by the present claims, comprising any peptide ligand for nectin-4, any spacer region, any cleavable linker and any toxin or having any structure that would meet the limitation of the claims of an undefined “bicycle toxin conjugate” that binds to nectin-4 or any icycle tumor targeted immune agonist specific for nectin-4.
The claims define the compounds to be administered to the patients in terms of their general type and their functional effect. However, naming of a compound in terms of its functional attributes – i.e., specific for nectin-4 - is not sufficient to describe that compound. More than a statement of biological function is required to satisfy the 35 USC 112 first paragraph, written description requirement for a specific compound.
Further, naming the compound a bicycle toxin conjugate does not sufficiently describe the overall structure of the compounds that are specific for nectin-4 and which are disclosed as to be used in the claimed methods for treating cancer in a subject having a copy number of the SDHC gene greater than two.
Further, as noted in Vas-Cath Inc. v. Mahurkar (19 USPQ2d 1111, CAFC 1991), the Federal Circuit concluded that:
"...applicant must also convey, with reasonable clarity to those skilled in art, that applicant, as of filing date sought, was in possession of invention, with invention being, for purposes of "written description" inquiry, whatever is presently claimed."
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision.
With respect to the present invention, there is no record or description which would demonstrate conception of a representative number of bicycle toxin conjugates specific for Nectin-4 or bicycle tumor targeted immune agonist specific for Nectin-4. Therefore, the claims fail to meet the written description requirement because the claims encompass a potentially large genus of bicycle toxin conjugates specific for Nectin-4 which are not described in the specification.Response to Remarks:
The response states:
“The present claims relate to methods for the identification and treatment of patients who are more likely to respond to therapy with a bicycle toxin conjugate or a bicycle tumor targeted immune agonist specific for Nectin-4, rather than the bicycle toxin conjugates or bicycle tumor targeted immune agonists per se. The claims are based on the observation that SDHC and Nectin-4 are frequently co-amplified in cancer patients, and that an increased SDHC copy number is associated with elevated Nectin-4 expression. At the time of filing, bicycle toxin conjugates and bicycle tumor targeted immune agonists specific for Nectin-4 were known in the art, and a skilled person would reasonably have expected patients who had an SDHC copy number of more than two to have improved treatment outcomes when treated with all bicycle toxin conjugates and bicycle tumor targeted immune agonists specific for Nectin-4 based on the teaching in the present application.”
These arguments have been fully considered but are not persuasive. The present claims require administering to the patient having a SDHC copy number greater than 4 a bicycle toxin conjugate specific for Nectin-4. Thus, the claimed methods require bicycle toxin conjugate specific for Nectin-4. As stated in the rejection, only the bicycle toxin conjugate specific for Nectin-4 of BT8009 is disclosed in the specification (p. 17). The specification does not teach that other bicycle toxin conjugates specific for Nectin-4 were known in the prior art. While the response asserts that bicycle toxin conjugates were known in the art, Applicant does not provide any evidence to support this conclusion.
See MPEP 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,” or by the establishment of a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,” or they may be “known in the art at the time of the filing date.’”
It is maintained that the claims fail to meet the written description requirement because the claimed methods require the use of a potentially large genus of bicycle toxin conjugates specific for nectin-4 and bicycle tumor targeted immune agonist specific for nectin-4, however, Applicant has not established that they were in possession of a representative number of species within the claimed genus.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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, Wu-Cheng Winston Shen can be reached on 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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