Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Claims 1-4 are pending and under consideration.
Priority
It is acknowledged that this application is a continuation application of U.S. Patent Appl. No. 17/089,103 filed November 4, 2020, which is a continuation application of U.S. Patent Appl. No. 14/767,936 filed August 14, 2015, which is the National Phase application of PCT/US2014/015758 filed February 11, 2024, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 61/765,329 filed February 15, 2013. The priority date for the pending claims has been established as February 15, 2013.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The Information Disclosure Statement filed on 03/07/2024 has been considered and entered by examiner.
Specification
The use of the terms Alexa (short for the mark ALEXAFLUOR) (page 7), DYLIGHT (page 7), and OREGON (page 7), which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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 1-4 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. This is a WRITTEN DESCRIPTION rejection.
The claims above recite the genus of a pituitary adenylate cyclase activating peptide (PACAP) and vasoactive intestinal peptide (VIP). Regarding PACAP, paragraph [00010] of the specification describes examples of this genus as SEQ ID NO. 1, any 29 to 37 residue fragment thereof. It is noted that this is not a special definition in the specification. For example, [00010] states: “In particular embodiments, the PACAP has the sequence of SEQ ID NO: 2”. SEQ ID NO: 2 has only 27 amino acids. Therefore, as mention above, these are only examples within the breadth of the claims’ terminology. Based on the specification’s use of fragments of PACAP, the broadest reasonable interpretation (BRI) of the claims’ limitation PACAP is full-length PACAP from any species and any fragment thereof. Also, SEQ ID NO: 7 has a non-natural amino acid in the specification (see paragraph [00012] of the specification). Thus, any mutated or substituted variants of a PACAP must also be interpreted as part of the claim scope. Regarding VIP, paragraph [00011] of the specification describes examples of this genus as SEQ ID NO. 3, or derivatives thereof. Similarly, given BRI, the claims’ limitation VIP is full-length VIP from any species, fragments thereof, and mutated or substituted variants of a VIP. However, there are not sufficient species taught in the specification to adequately describe such genus breadth. Rather, only three functional species of PACAP are set forth, SEQ ID NOs: 1, 2, and 7 which can bind to VPAC receptors (thus can be used in the claimed method). The specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
To satisfy the written description requirement for this claimed genus (PACAP),
Applicant must adequately describe representative peptides to reflect the structural
diversity of the claimed genus. See Eli Lilly, 119 F .3d at 1568 ("[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material."); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) ("Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.").
Functionally defined genus claims, such as in the instant case which requires a genus of PACAP and VIP that bind tumor cells, can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."). The peptide arts are unpredictable, since any mutation/modification can dramatically change or lead to loss of function. For example, Liao (Liao et al., Current Topics in Medicinal Chemistry, 2019, Vol. 19, No. 16, 1399-1417, Publication Year: 2019) teaches that a modification at a single position (position 3) of PACAP reduces affinities for all receptors (page 1407, col. 2, para. 1). Liao also teaches that the secondary structure at the N-terminus of the PACAP is an important determinant of receptor specificities (page 1407, col. 2, para. 1). Liao teaches that although PACP and VIP share high sequence identity (~60%), they have different binding specificity and functional domains (see Fig. 5).
The instant specification teaches only three functional species of PACAP (SEQ ID NOs: 1, 2, and 7) which can bind to VPAC receptors. The specification also teaches that these PACAPs can be used to detect prostate cancer cells in urine sample of the patients (see Example 1). Prior art (see Thakur in 103 rejection below) also teaches a couple PACAPs, including PACAP27 and PACAP38, which can bind VPAC receptors and can be used to detect tumor cells overexpressing VPAC receptors (see [0011] of Thakur). It is noted that PACAP38 and PACAP27 have the sequences of SEQ ID NO: 1 and SEQ ID NO: 2 of the instant application, respectively.
In view of above, the three species disclosed by the specification and prior art can’t represent the genus of PACAP and VIP broadly claimed.
Since only three peptides in the instant specification are taught that function in the claimed methods, the instant claims fail the written description requirement. A representative number of species has not been disclosed. The entire genus claimed has not been sufficiently represented. Thus, the claims are rejected.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 3-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a nature phenomenon, or an abstract idea) without significantly more.
The claims are directed to the natural correlation (a law of nature) between increased binding to cells overexpressing PACAP receptors and circulating cancer cells in specific biological samples. Said correlation being used to diagnosis cancer. These judicial exceptions are not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Under the broadest reasonable interpretation (BRI), the terms of the claims are presumed to have their plain meaning consistent with the specification as it would be interpreted by one of ordinary skill in the art. See MPEP 2111.01.
The claims are to processes, which fall in one of the statutory categories of invention. See MPEP 2106.03.
As explained in MPEP 2106.04(11) and the October 2019 Update, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. The eligibility analysis comprises three-step tests: Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
1) Step 2A Prong one: evaluating whether the claim recites a judicial exception (MPEP 2106.3); 2) Step 2A Prong two: evaluating whether the claim as a whole integrates the recited judicial exception into a practical application of the exception (MPEP 2106.4); 3) Step 2B: evaluating whether the claim as a whole amounts to significantly more than the recited exception (MPEP 2106.5).
The present claims are directed to a process so Step 1 is satisfied.
Step 2A, Prong 1 – does the claim recite a judicial exception? Yes, as set forth above, claims 3-4 recite the natural correlation (a law of nature) between increased binding to cells overexpressing PACAP receptors of shed or circulating cancer cells in specific biological samples and diagnosis of cancers.
Step 2A Prong Two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. 2019 PEG Section III(A)(2), 84 Fed. Reg. at 54-55.
Besides the law of nature, claims 3-4 recite circulating or shed tumor cells, PACAP-based probes and biological samples at a high level of generality. Under Step 2A, Prong 2, these additional elements serve merely to gather data that is utilized as input to the recited judicial exception. Therefore, these steps equate to insignificant extra-solution activity and are insufficient to integrate into a practical application. (Step 2A: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. The previous considerations from Step 2A, Prong 2 are carried over and we re-evaluate the additional elements for their conventionality, both individually and in combination. In looking at the additional elements, they appear to be conventional both individually and in combination in light of prior art. First, the labeled PACAP probes are taught by Thakur (Thakur et al., US 2003/0129133 A1, Publication Date: 07/10/2003, in IDS), as discussed infra in the rejection over obviousness. Thus, said probes are well-understood, routine, and conventional in the art. Thakur teaches their use in detection of cancer cells ([0017]). Thus, even the recited use of the labeled PACAP is well-understood, routine, and conventional. Fujita (Fujita et al., Human Pathology, 2009, 40, 924-933, Publication Year: 2009, in IDS) further teaches: 1) identifying prostate cancer cells in a biological sample, including samples of any tissue or fluid in which prostate cancer cells are present; 2) detecting prostate cancer cells shed in urine for diagnosis, as discussed infra in the rejection over obviousness. Thus, these routine, well-understood, and conventional additional elements do not add an inventive concept to the instant claim.
Taken all together, the presence of a judicial exception in the claims, and the absence of any additional claim limitation that is more than what is already well-understood, routine, and conventional in the art, the instant claims above do not amount to significantly more than the judicial exception they contain and are rejected here.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-4 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Thakur (Thakur et al., US 2003/0129133 A1, Publication Date: 07/10/2003, in IDS) in view of Fujita (Fujita et al., Human Pathology, 2009, 40, 924-933, Publication Year: 2009, in IDS).
Thakur teaches that tumors expressing VPAC receptors can be imaged with compounds comprising PACAP (Abstract).
Thakur teaches radiolabeled agents for tumor imaging ([0002] and [0016]).
Thakur teaches that prostate tumor cells express VPAC receptors ([0013]).
Thakur teaches a method of detecting tumors expressing VPAC receptors comprising administering an effective amount of an imaging compound to a subject ([0017]). And this compound comprises a PACAP and a radionuclide ([0017]).
Thakur teaches two PACAPs: PACAP38 of SEQ ID NO: 1 and PACAP27 of SEQ ID NO: 2 ([0065]), the two PACAP have similar activity ([0011]). It is noted that SEQ ID NO: 1 and SEQ ID NO: 2 of Thakur are the same as SEQ ID NO: 1 and SEQ ID NO: 2 of the instant application, respectively.
Thakur teaches multiple imaging radionuclides ([0087]).
Thakur teaches that after administration of the compound, a scintigriphic image is generated ([0017]). The scintigriphic image is generated after sufficient time has passed to allow the administered imaging compound will reach the tumor and bind to PACAP and VPAC receptor on tumor cells ([0094]). Thus, the label of the PACAP probe (radiolabel) is visualized and binding to VPAC receptor on tumor cells is determined by visualization.
Thakur teaches that the imaging compound can be used to detect VPAC-expressing tumors in a subject, who has such a tumor, like a prostate tumor ([0089] and claim 13).
Thakur teaches a specific labeled PACAP through a spacer: 99mTc-TP3475, which is PACAP-27 with the C-terminal GABA spacer and G-A(D)-G-G chelating agent (see Example 1 and Example 2, [0110]).
Thakur teaches that the biological activity of TP3475 was not compromised due to the addition of the spacer and chelating agent to the C-terminus of PACAP27 (Example 4).
Thakur teaches that 99mTc-TP3475 can be detected in urine sample of mice (Example 5).
Thakur does not explicitly teach detecting shed or circulating tumor cells in biological fluid such as urine.
Fujita teaches that prostate cancer biomarkers are enriched in urine (Abstract). This is because both prostate cancer cells and prostate epithelial cells can be visualized through immunostaining techniques comprising detecting a prostate cancer marker AMACR and a prostate epithelical cell marker Nkx3.1 in urine (Abstract, and Title). Their technique led to identification of prostate cancer patients and no false positives (Abstract).
Fujita teaches that their method is applicable to prostate cancer diagnosis (Abstract).
Fujita teaches that detecting prostate cancer cells shed in urine, in conjunction with biomarkers and improved imaging modalities, may provide an alternative method for prostate cancer diagnosis (the bridging paragraph of cols 1-2 on page 925).
Fujita teaches a fluorescence microscopic evaluation (page 927, col. 1, and Figs. 1 & 2).
Fujita teaches fluorescently labeled antibodies (labeled proteins) were used for visualization (§ 2.4.2 Immunofluorescence).
Taken together, use of tagged peptides that are specific to prostate cancer in fluid sample (e.g. urine) are rendered obvious by the teachings of Fujita combined with the teachings of Thakur.
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of Thakur and Fujita, to fluorescently label a PACAP peptide (e.g. PACAP27) so that it could be used in the method of Fujita, a less invasive test than biopsy, for detection of prostate cancer cells in patient urine samples since Thakur teaches that a related and functionally equivalent probe can detect prostate cancer cells and Fujita validated their diagnostic methods as functional for prostate cancer. The obvious fluorescent PACAP probe could be added to the method of Fujita for the advantage of improving its sensitivity, providing two probes for prostate cancer cells rather than one. Detection of multiple biomarkers for cancer is well-known in this art to improve diagnostic assay sensitivity. This is owed to cancer cells having varying levels of their markers. The motivation would have been to improve detection/diagnostic sensitivity and/or specificity.
Taken all together, the combined teachings above clearly render obvious the instant claims for the advantages discussed supra which would be readily appreciated and recognized by one of ordinary skill in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 6855308 (hereinafter, Pat. 308) in view of Thakur (Thakur et al., US 2003/0129133 A1, Publication Date: 07/10/2003, in IDS) in view of Fujita (Fujita et al., Human Pathology, 2009, 40, 924-933, Publication Year: 2009, in IDS).
The claims of Pat. 308 teach a method of detecting tumors expressing VPAC receptors in a subject who has, or is suspected of having, such a tumor, said method comprising: 1) administering an effective amount of an imaging compound of formulae A or B to the subject; (2) generating a scintigraphic image of at least part of the subject… (claim 1). It is noted that formulae A or B comprising an imaging radionuclide and a PACAP. Thus, the claims of Pat. 308 teach a method of detecting tumors with a labeled PACAP.
The claims of Pat. 308 teach detecting prostate cancer with the labeled PACAP probe (claim 13).
However, the claims of Pat. 308 do not teach detecting shed or circulating tumor cells, or diagnosis cancer by detecting binding of shed or circulating tumor cells.
The combined teachings of Thakur and Fujita are discussed above and just this group of art renders all the instant claims obvious as discussed supra. Therefore, the addition of the patented claims only further supports the argument of obvious.
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Pat. 308, Thakur and Fujita, to use labeled PACAP peptide of the claims of Pat. 308 in the method of Fujita, a less invasive test than biopsy, for detection of prostate cancer cells in patient urine samples since Thakur teaches that a related and functionally equivalent probe can detect prostate cancer cells and Fujita validated their diagnostic methods as functional for prostate cancer. The obvious labeled PACAP probe could be added to the method of Fujita for the advantage of improving its sensitivity, providing two probes for prostate cancer cells rather than one. Detection of multiple biomarkers for cancer is well-known in this art to improve diagnostic assay sensitivity. This is owed to cancer cells having varying levels of their markers. The motivation would have been to improve detection/diagnostic sensitivity and/or specificity.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/ Primary Examiner, Art Unit 1646
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