DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 30, 2025, has been entered.
Election/Restrictions
Applicant's election with traverse of Species A (i.e., a single and specific lymphocyte as a T cell exposed to a tumor antigen that is extracted from leukapheresis, does not contain tumor infiltrating lymphocytes, and is not transduced with a vector encoding a TCR that recognizes a cancer antigen), and Species B (i.e., a single and specific VIP antagonist as VIP-hyb) in the reply filed on 9/18/24 is acknowledged. The traversal is on the grounds that species B election is not appropriate given that there are 16 VIP antagonists thereby representing a finite number of species and constituting a reasonable number of species to search (See Applicant’s Response received on 9/18/24, pg. 3). Similarly, Applicants assert that Species A election is not appropriate given there are a finite number of species for each subspecies thereby constituting a reasonable number of species to search (See Applicant’s Response received on 9/18/24, pg. 3).
This is not found persuasive. Regarding Species B, it is noted that the scope of the claimed VIP antagonist is not limited to 16 species, but rather encompasses any number of VIP antagonists. It is further noted that the instant specification defines a VIP antagonist as any molecule that inhibits or detracts from the ability of VIP to alter immune responses (See instant specification, [0071]) (emphasis added). Although examples of VIP antagonists are discussed (See instant specification, [0011], [0071]), the broadest reasonable interpretation of what constitutes a VIP antagonist as instantly claimed is not limited to these examples in light of the definition of a VIP antagonist. Therefore, contrary to Applicant’s argument, there are not a finite number of species claimed constituting a reasonable number of species to search.
Regarding Species A, although considering each subspecies individually may appear limited in scope, Applicants are respectfully reminded that the consideration for each subspecies is to be done as whole. Assuming arguendo that Applicants determination for the number of options for each subspecies is correct, that is a total of 15 different options with a far greater number of potential combinations between the 15 options; for example 1 species of A-1 with each of the 2 species of A-2, with each of the 3 species of A-3, with each of the 4 species of A-4, and with each of the 2 species of A-5. Thus, contrary to Applicant’s argument, there are not a finite number of species claimed constituting a reasonable number of species to search.
The requirement is still deemed proper and is therefore made FINAL.
Please note that Species A is expanded to include where the T cells are extracted from blood.
Status of Claims
Claims 1-20 were originally filed on October 10, 2022.
The amendment received October 10, 2022, canceled claims 1-16; and amended claims 17-19; and added new claims 21-34. The amendment received on April 16, 2025, canceled claim 24; and amended claims 17-23, 25-26, and 28-34. The amendment received on December 30, 2025, canceled claims 26-27; amended claims 17-20, 28, and 32-34; and added new claim 35.
Claims 17-23, 25, and 28-35 are currently pending and claims 17-18, 20-21, 28-29, 31-32, and 34-35 are under consideration as claims 19, 22-23, 25, 30, and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on September 18, 2024.
Priority
The present application is a division of a divisional of U.S. Non-Provisional Application No. 15/601,352, now issued as U.S. Patent No. 11,464,855, which is a divisional of U.S. Non-Provisional Application No. 13/979,003, now issued as U.S. Patent No. 9,669,092, which claims status as a 371 (National Stage) of PCT/US2012/023268 filed January 31, 2012, and claims priority under 119(e) to U.S. Provisional Application Nos. 61/467,714 filed on March 25, 2011, and 61/438,707 filed February 2, 2011.
Sequence Interpretation
For claims 17, 28, and 32, please note that the Examiner is interpreting the scope as open-ended encompassing any peptide with a C-terminal amide that exhibits the function of antagonizing VIP where the N-terminus encompasses any N- and/or C-terminal additions but the C-terminus is capped with an amide. Regarding a VIP antagonist that is a peptide having a C-terminal amide, it is noted that the instant specification teaches that VIP antagonists are known including VIP analogues, VIP fragments, growth hormone-releasing factor analogs and hybrid peptides.....Some examples of VIP antagonists include the following and variants thereof: [Ac-Tyr1,D-Phe2]GRF 1-29, amide, i.e., (SEQ ID NO:4) YFDAIFTNSYRKVLGQLSARKLLQDIMSR (Modifications: Tyr-1=N-terminal Ac, Phe-2=D-Phe, Arg-29=C-terminal amide); VIP (6-28), i.e., (SEQ ID NO: 5) FTDNYTRLRKQMAVKKYLNSILN (Modifications: Asn-23=C-terminal amide); [D-p-Cl-Phe6, Leu17]-VIP, i.e., (SEQ ID NO:6) HSDAVFTDNYTRLRKQLAVKKYLNSILN (Modifications: Phe-6=p-CI-D-Phe, Asn-34=C-terminal amide); VIP-hyb also known as VIPhybrid, i.e., a hybrid peptide of neurotensin and VIP consisting of an N-terminal (SEQ ID NO: 7) KPRRPY, also designated neurotensin (6-11)] followed by the C-terminal 22 amino acids of VIP, i.e., (SEQ ID NO: 8) TDNYTRLRKQMAVKKYLNSILN, also designated VIP (7-28); N-terminal Stearyl, Norleucine 17 VIPhyb, i.e., (SEQ ID NO: 9) KPRRPYTDNYTRLRKQXAVKKYLNSILN, wherein St is Stearyl and X is norleucine; Ac His1 [D-Phe(2), Lys(15), Arg(16), Leu(27)]-VIP(1-7)/GRF(8-27), i.e., (SEQ ID NO:10) HFDAVFTNSYRKVLKRLSARKLLQDIL, C-terminal amide; and pituitary adenylate cyclase-activating polypeptide, PACAP (6-38) C-terminal amide, i.e., (SEQ ID NO:11) TDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNK (See specification, paragraph [0071]). The specification also incorporates three U.S. Patents by reference (See specification, paragraph [0071]). One of the cited US Patents, i.e., Burman et al. US Patent No. 6,828,304 B1, teaches a specific VIP antagonist peptide sequence of X-LMYPTYLK-Y where X is a straight, branched or cyclic alkanoyl group of 3-16 carbon atoms, and the C-terminal Y is a carboxy terminal residue selected from OH or amino (See Burman specification, col. 2, lines 19-48; col. 3, lines 9-19). The second cited US Patent, i.e., Burman et al. US Patent No. 7,094,755 B2, teaches VIP antagonists where the natural VIP amino acid sequence contains three residues with alpha,alpha-dialkylated amino acids; more specifically, the residue at position 4 is Aib, Deg, or Ac5c, the residue at position 6 is Phe or 4-Cl-D-Phe, and the residue at position 17 is Met, Leu, Dpg, or a hydrolysable carboxy protecting group (See Burman specification, col. 4, lines 1-45). The last cited US Patent is Gozes et al. US Patent No. 5,565,424, which teaches VIP antagonists having the amino acid sequence of R1-KPRRPYTDNYTRLRKQ-X1-A-X2-KKYLNSIL-AsnNH-R2 where R1 and R2 can be functional groups, X1 and X2 are any natural amino acid or amino acid mimetic provided that X2 is not Met (See Gozes specification, col. 3, lines 45-67 to col. 4, lines 1-14). As such, given the species taught in the specification combined with the pre-existing knowledge in the art regarding VIP antagonists that are a peptide having a C-terminal amide, an ordinary skilled artisan would have put one in possession of the claimed genus. Thus, an ordinary skilled artisan would conclude that the applicant was in possession of the claimed genus at the time the application was filed.
For claims 20 and 34, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 9 where X is Met and has a C-terminal amide but where the sequence can have additional residues at the N-terminal end (note: the C-terminal amide caps the C-terminal end of the sequence from additional residues via a natural peptide bond).
Response to Arguments
Applicant’s arguments, see Response, filed 12/30/25, with respect to the claim objection have been fully considered and are persuasive. The objection of claim 32 has been withdrawn.
Applicant’s arguments, see Response, filed 12/30/25, with respect to the 112(b) rejection have been fully considered and are persuasive. The rejection of claim 18 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 has been withdrawn.
Applicant’s arguments, see Response, filed 12/30/25, with respect to the 112(a), written description, rejection have been fully considered and are persuasive. The rejection of claims 27 and 32 as failing to comply with the written description requirement has been withdrawn.
Applicant’s arguments, see Response, filed 4/16/25, with respect to the 112(a), scope of enablement, rejection have been fully considered and are persuasive. The rejection of claims 26-29, 31-32, and 34 as failing to comply with the enablement requirement has been withdrawn.
New Rejections
Claim Rejections - 35 USC § 103
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 negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 28-29, 31 and 34-35 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lamb WO 00/44893 A1 published on August 3, 2000, in view of Mukherjee et al. CA Publication No. 2,197,139 A1 published on February 17, 1998 (cited in the IDS received on 4/11/23).
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 28-29, 31, and 35, with respect to a method of treating a cancer in a subject having a cancer by obtaining a T cell, expanding the T cell in vitro, and transferring the in vitro expanded T cell into the subject as recited in instant claim 28; with respect to where the T cell is extracted from blood as recited in instant claim 29; and with respect to where the T cell is expanded in vitro by exposing the T cell to IL-2 and/or tumor antigen as recited in instant claim 31:
Lamb claims a method of treating leukemia by administering to a leukemic patient a suitable amount of substantially purified γδ+ T cells and monitoring the patient for the presence of leukemia (See Lamb, claim 4; pg. 11, 4th paragraph; Figure 5). Lamb also claims a method of preparing substantially purified γδ+ T cells by incubating donor γδ+ T cells with irradiated recipient leukemia to allow activation and expansion of γδ+ T cells and harvesting the γδ+ T cells (See Lamb, claim 7). As such, Lamb teaches a method of treating a cancer where the cancer is leukemia in a subject having leukemia by obtaining a T cell (note = incubating donor γδ+ T cells necessarily requires obtaining the γδ+ T cells), expanding the T cell, and administering (note: same as transferring) the expanded T cell into the subject as recited in instant claims 28 and 35. Moreover, Lamb teaches that the recipient leukemia cells were obtained from blood of the recipient and separated from normal mononuclear cells (MNC) using gradient centrifugation (See Lamb, pg. 7, last paragraph). Donor γδ+ T cells were obtained from peripheral blood, which were purified in the MNC layer by negative selection using CD4+ and CD8+ immunomagnetic microspheres (See Lamb, pg. 8, 1st paragraph). These purified donor γδ+ T cells were plated is tissue culture with TCR-δ1 pan-δ monoclonal antibody in PBS to facilitate initial activation and expansion of γδ+ T cells (See Lamb, pg. 8, last paragraph). Irradiated primary leukemic blasts from the recipient were re-suspended in AIM-5 media with 15% PBS and 25IU of IL-2 (See Lamb, pg. 8, last paragraph). This suspension was added to the coated wells (See Lamb, pg. 8, last paragraph). At week four, fold expansion was calculated and harvesting began (See Lamb, pg. 8, last paragraph to pg. 9, 1st paragraph). As such, Lamb teaches that the T cells were expanded in vitro and exposed to IL-2 and a tumor antigen, i.e., leukemic tumor antigen necessarily present on the recipient’s leukemic cells, as recited in instant claims 28 and 31.
For claims 28 and 34-35, with respect to a method of treating a cancer in a subject having a cancer by administering a VIP antagonist that is a peptide having a C-terminal amide to the subject as recited in instant claim 28; with respect to where the VIP antagonist is a peptide having a C-terminal amide and is modified with hydrocarbon or polyethylene glycol groups and wherein the peptide has SEQ ID NO: 9 where X is M as recited in instant claim 34; and with respect to where the cancer is leukemia:
Lamb does not expressly teach co-administering a VIP antagonist that is a peptide having a C-terminal amide in combination with expanded T cells.
As discussed below for claim 28, Mukherjee et al. teaches a pharmaceutical composition for use in killing or inhibiting multiplication of tumor cells as well as cancer cells (See Mukherjee specification, pg. 2, last paragraph) or for use in preventing, inhibiting, or modulating the hypersecretion of VIP, somatostatin, bombesin, Substance P, or a combination thereof (See Mukherjee specification, pg. 2, last paragraph to pg. 3, 1st paragraph). The composition may comprise a therapeutically effective combination of peptide analogs of somatostatin, VIP, bombesin, and Substance P (See Mukherjee specification, pg. 3, 1st paragraph). In particular, Mukherjee et al. teaches that the VIP analog can be VIP1 (a VIP antagonist), VIP2 (a VIP receptor binding inhibitor), or VIP3 (a VIP receptor antagonist) (See Mukherjee specification, pg. 3, 1st paragraph). The amino acid sequence of VIP1 is depicted in Table 2 as SEQ ID NO: 1 (See Mukherjee specification, pg. 8, Table 2), which is identical to instant SEQ ID NO: 9 where X is M. Additionally, Mukherjee et al. teaches that the cytotoxicity of each peptide analog including VIP1 was tested against a variety of cancer cell lines including human colon adenocarcinoma cells (See Mukherjee specification, pg. 8, last paragraph). As depicted in Table 7, VIP1 exhibited a cytotoxic effect against a number of cancers including on human colon adenocarcinoma cells (i.e., HT29, SW620 and PTC cell lines), human leukemia cells (i.e., K562 cell line), human lymphoma cells (i.e., MOLT-4 cell line) (See Mukherjee specification, pg. 9, Table 7). Moreover, Mukherjee et al. examined the cytotoxicity of a combination therapy comprising different peptide analogs where each combination tested includes VIP1 at a concentration of 10-7 M and each combination exhibited cytotoxicity against human colon adenocarcinoma cells (See Mukherjee specification, pg. 14, Table 7). One of the peptide analog combinations is referred to as MuJ-7 (See Mukherjee specification, pg. 8, Table 7). In Example 4, Mukherjee examined the cytotoxicity of the MuJ-7 combination therapy on 13 human tumor cell lines including human leukemia and lymphoma cell lines (See Mukherjee specification, pg. 15, last paragraph to pg. 16, 1st paragraph; Table 15A). As depicted in Figure 15A, the MuJ-7 combination therapy, which includes VIP1, exhibited about 45% cytotoxicity against the human leukemia cells and about 81% cytotoxicity against the human lymphoma cells (See Mukherjee specification, pg. 16, Table 15A). Since the scope of the method of instant claim 28 utilizes the transitional phrase “comprising”, the peptide analog combination therapy taught by Mukherjee is encompassed by the instant method. Thus, Mukherjee demonstrates that VIP1 alone or in combination with other peptide analogs including other VIP antagonists treat leukemia in a subject. Therefore, the teachings of Mukherjee et al. satisfy the claim limitations as recited in claim 35 with respect to administering a VIP antagonist that is a peptide having an C-terminal amide and has the amino acid sequence of instant SEQ ID NO: 9 where X is M to a subject having leukemia in order to treat the leukemia in the subject.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Lamb and/or Mukherjee et al. do not expressly teach a method of treating leukemia in a subject having leukemia by obtaining a T cell, expanding the T cell in vitro, transferring the in vitro expanded T cell into the subject, and administering a VIP antagonist that is a peptide having an C-terminal amide to the subject as recited in instant claims 28 and 35; and wherein the VIP antagonist is modified with hydrocarbon groups and has the amino acid sequence of SEQ ID NO: 9 where X is Met as recited in claim 34. However, by combining the teachings of Lamb and Mukherjee et al. these deficiencies are cured by constituting the combination of prior art elements according to known methods to yield predictable results pursuant to KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a method of treating leukemia in a subject having leukemia by obtaining a T cell, expanding the T cell in vitro, transferring the in vitro expanded T cell into the subject, and administering a VIP antagonist that is a peptide having an C-terminal amide to the subject as recited in instant claims 28 and 35; and wherein the VIP antagonist is modified with hydrocarbon groups and has the amino acid sequence of SEQ ID NO: 9 where X is Met as recited in claim 34, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Lamb and Mukherjee et al. and treat leukemia in a subject having leukemia by utilizing the combination of (1) obtaining γδ+ T cells extracted from blood of a donor, expanding the γδ+ T cells in vitro including exposing them to IL-2 and extracted leukemic cells from the recipient patient, and administering the expanded γδ+ T cells to the recipient patient with (2) administering a VIP antagonist such as a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated alone or in combination with additional peptide analogs to form the MuJ-7 peptide analog combination to the subject in order to treat leukemia in the subject. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because administering a VIP antagonist such as a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated to a subject alone or in combination with additional peptide analogs to form the MuJ-7 peptide analog combination was known to treat leukemia as taught by Mukherjee et al.; and because obtaining a γδ+ T cells from donor blood, expanding the γδ+ T cells in vitro including exposing them to IL-2 and extracted leukemic cells from the recipient patient, and administering the expanded δ+ T cells to the subject was known to treat leukemia in a subject as taught by Lamb. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the VIP antagonist a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated alone or in combination with additional peptide analogs to form the MuJ-7 peptide analog combination of Mukherjee et al. and the expanded γδ+ T cells of Lamb were administered to a subject having leukemia to treat the leukemia. Therefore, "it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art." (MPEP 2144.06). In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from their having been individually taught in prior art. Therefore, since each of the references teach agents that are effective in treating leukemia, it would have been obvious to combine the two agents with the expectation that such a combination would be effective in treating leukemia. Thus, combining them flows logically from their having been individually taught in prior art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Maintained/Modified Rejections in light of Applicants’ Amendments
Claim Rejections - 35 USC § 103
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 negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 28, 31, and 34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Winqvist et al. WO 2010/006808 A1 published on January 21, 2010, in view of Mukherjee et al. CA Publication No. 2,197,139 A1 published on February 17, 1998 (cited in the IDS received on 4/11/23). Please note that the rejection has been updated in light of Applicants’ amendments.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 28 and 31, with respect to a method of treating a cancer in a subject having a cancer by obtaining a T cell, expanding the T cell in vitro, and transferring the in vitro expanded T cell into the subject as recited in instant claim 28; and with respect to where the T cell is expanded in vitro by exposing the T cell to tumor antigen as recited in instant claim 31:
Winqvist et al. teaches expanding tumor-reactive T-lymphocytes (note: same as T-cells) from sentinel lymph nodes demonstrating that it is possible to culture T-lymphocytes obtained sentinel lymph nodes (See Winqvist specification, pg. 9, 1st paragraph). These expanded tumor-reactive T-lymphocytes can treat cancer by administering an effective amount of tumor-reactive T-lymphocytes to the patient from which the sentinel nodes were removed (See Winqvist specification, pg. 9, 1st paragraph; pg. 17, 1st paragraph; pg. 25, 2nd paragraph). The relevant T-lymphocytes are obtained by a method for expansion of tumor-reactive CD4+ helper and/or CD8+ T-lymphocytes (See Winqvist specification, pg. 9, 2nd paragraph). The success of a cancer treatment comprising administration of tumor-reactive T-lymphocytes are determined by factors such as, e.g., the amount of tumor-reactive T-lymphocytes obtained after expanding from a sentinel node, i.e., the amount of tumor-reactive T-lymphocytes available for infusion to the patient, the time required to obtain an effective amount of tumor-reactive T-lymphocytes and the concentration and ratio of specific subpopulations of tumor-reactive T-lymphocytes obtained by the expansion method used (See Winqvist specification, pg. 13, last paragraph to pg. 14, 1st paragraph). Winqvist et al. also teaches that the cancer to be treated includes any solid neoplasm of epithelial, mesenchymal, or embryological origin in any anatomical location including colorectal, breast, renal cell, ovarian, lung, and prostate cancer (See Winqvist specification, pg. 22, last paragraph; pg. 23, 1st paragraph; pg. 25, 3rd paragraph to pg. 26, 1st paragraph). It is noted that although Winqvist et al. teaches that the tumor-reactive T-lymphocytes are co-administered with an antiangiogenic component (See Winqvist specification, pg. 14, 2nd paragraph; pg. 16, 3rd paragraph), the scope of the instantly claimed method does not exclude additional components given the use of the transitional phrase, “comprising”.
Furthermore, Winqvist et al. teaches one preferred procedure where a VEGF inhibitor is administered approximately 3 weeks before harvest of sentinel or metinel node acquired lymphocytes (SNALs and MNALs) (See Winqvist specification, pg. 30, 1st paragraph). The SNALs and MNALs are administered approximately 4 weeks after harvest (See Winqvist specification, pg. 30, 1st paragraph). Alternatively, a combination therapy can be initiated with administration of a VEGF inhibitor followed by administration of tumor-reactive T-lymphocytes (See Winqvist specification, pg. 9, 6th paragraph).
Furthermore, in Example 1, Winqvist et al. teaches that sentinel nodes were identified and marked perioperatively around a tumor with blue dye (See Winqvist specification, pg. 31, last paragraph). The marked nodes were then removed (See Winqvist specification, pg. 32, 1st paragraph). The sentinel node material was kept on ice and immediately taken care of using AIM V® Media at all times, and single cell suspensions of sentinel node lymphocytes were obtained through gentle homogenization in a loose fit glass homogenisator (See Winqvist specification, pg. 32, 3rd paragraph). The sentinel node lymphocytes were then put in cell culture flasks at 4 million cells/ml and interleukin-2 (IL-2) was added (See Winqvist specification, pg. 32, 3rd paragraph) thereby constituting where the lymphocyte is exposed to IL-2 as recited in instant claim 31. Autologous tumor extract was also prepared by homogenization and added to the cell culture at a concentration of 1/100 (See Winqvist specification, pg. 32, 4th paragraph) thereby constituting where the lymphocyte is exposed to a tumor antigen as recited in instant claim 31. Expansion of the lymphocyte then occurred (See Winqvist specification, pg. 32, last paragraph). Winqvist et al. then teaches that the day before transfusion to the patient the cell cultures were subject to purification in order to retrieve the viable cells in the culture (See Winqvist specification, pg. 33, 1st paragraph). As such, Example 1 demonstrates expanding T lymphocytes extracted from a patient where the T lymphocytes were exposed to IL-2 and a tumor antigen in vitro thereby satisfying the claim limitations with respect to obtaining a T cell and expanding the T cell in vitro as recited in instant claim 28 where the T cell is expanded in vitro by exposing it to IL-2 and a tumor antigen as recited in instant claim 31.
In example 2, Winqvist et al. teaches that sentinel and metinal lymph nodes from colon cancer patients were removed, and expanded as described in example 1 supra (See Winqvist specification, pg. 34, 3rd paragraph to pg. 35, 2nd paragraph). The expanded autologous T cells were infused back into the patients in which they were extracted from (See Winqvist specification, pg. 35, 3rd paragraph). The patients were followed for 36 months on average where improved cancer diagnosis was observed in at least 7 of the 16 patients (See Winqvist specification, pg. 35, last paragraph). As such, Example 2 demonstrates transferring the in vitro expanded T cell into the subject as recited in instant claim 28. Therefore, the teachings of Winqvist et al. suggest treating a cancer in a subject having cancer by obtaining a T cell, expanding the T cell in vitro, and transferring the in vitro expanded T cell into the subject as recited in instant claim 28 where the T cell is expanded in vitro by exposing it to IL-2 and a tumor antigen as recited in instant claim 31.
For claims 28 and 34, with respect to a method of treating a cancer in a subject having a cancer by administering a VIP antagonist that is a peptide having a C-terminal amide to the subject as recited in instant claim 28; with respect to where the VIP antagonist is a peptide having a C-terminal amide and is modified with hydrocarbon or polyethylene glycol groups and wherein the peptide has SEQ ID NO: 9 where X is M as recited in instant claim 34:
Winqvist et al. teaches that the cancer treatment can be supplemented with any other relevant treatment for cancer (See Winqvist specification, pg. 28, 4th paragraph). However, Winqvist et al. does not expressly teach that the other relevant treatment is a VIP antagonist that is a peptide having a C-terminal amide.
Mukherjee et al. teaches a pharmaceutical composition for use in killing or inhibiting multiplication of tumor cells as well as cancer cells (See Mukherjee specification, pg. 2, last paragraph) or for use in preventing, inhibiting, or modulating the hypersecretion of VIP, somatostatin, bombesin, Substance P, or a combination thereof (See Mukherjee specification, pg. 2, last paragraph to pg. 3, 1st paragraph). The composition may comprise a therapeutically effective combination of peptide analogs of somatostatin, VIP, bombesin, and Substance P (See Mukherjee specification, pg. 3, 1st paragraph). In particular, Mukherjee et al. teaches that the VIP analog can be VIP1 (a VIP antagonist), VIP2 (a VIP receptor binding inhibitor), or VIP3 (a VIP receptor antagonist) (See Mukherjee specification, pg. 3, 1st paragraph). The amino acid sequence of VIP1 is depicted in Table 2 as SEQ ID NO: 1 (See Mukherjee specification, pg. 8, Table 2). When comparing Mukherjee et al.’s SEQ ID NO: 1 with presently claimed SEQ ID NO: 9 where X is Met, there is 100% identity. Moreover, the C-terminus of Mukherjee et al.’s SEQ ID NO: 1 is amidated. As such, Mukherjee et al.’s SEQ ID NO: 1 constitutes a VIP antagonist that is a peptide having a C-terminal amide as recited in claim 28.
Additionally, Mukherjee et al. teaches that the cytotoxicity of each peptide analog including VIP1 was tested against a variety of cancer cell lines including human colon adenocarcinoma cells (See Mukherjee specification, pg. 14, last paragraph). As depicted in Table 7, VIP1 exhibited a cytotoxic effect on human colon adenocarcinoma cells (See Mukherjee specification, pg. 14, Table 7). Moreover, as depicted in Table 8, VIP1 exhibited a cytotoxic effect on PTC (human colon tumor cells) (See Mukherjee specification, pg. 15, Table 8; pg. 16, 1st paragraph). Thus, Mukherjee et al. teaches a method for treating a subject having colon cancer by administering a VIP antagonist where the VIP antagonist is a peptide having a C-terminal amide where the C-terminal amidation constitutes modification with hydrocarbon groups and has the amino acid sequence of instant SEQ ID NO: 9 where X is M. Therefore, the teachings of Mukherjee et al. satisfy the claim limitations as recited in claims 28 and 34 with respect to administering a VIP antagonist that is a peptide having an C-terminal amide and has the amino acid sequence of instant SEQ ID NO: 9 where X is M to a subject having cancer in order to treat the cancer in the subject.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Winqvist et al. and/or Mukherjee et al. do not expressly teach a method of treating a cancer in a subject having cancer by obtaining a T cell, expanding the T cell in vitro, transferring the in vitro expanded T cell into the subject, and administering a VIP antagonist that is a peptide having an C-terminal amide to the subject as recited in instant claim 28; with respect to where the T cell is expanded in vitro by exposing the T cell to a tumor antigen as recited in instant claim 31; and wherein the VIP antagonist is modified with hydrocarbon groups and has the amino acid sequence of SEQ ID NO: 9 where X is Met as recited in claim 34. However, by combining the teachings of Winqvist et al. and Mukherjee et al. these deficiencies are cured by constituting the combination of prior art elements according to known methods to yield predictable results pursuant to KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a method of treating a subject having cancer by obtaining a T cell, expanding the T cell in vitro, transferring the in vitro expanded T cell into the subject, and administering a VIP antagonist that is a peptide having an C-terminal amide to the subject as recited in instant claim 28; with respect to where the T cell is expanded in vitro by exposing the T cell to a tumor antigen as recited in instant claim 31; and wherein the VIP antagonist is modified with hydrocarbon groups and has the amino acid sequence of SEQ ID NO: 9 where X is Met as recited in claim 34, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Winqvist et al. and Mukherjee et al. and treat colon cancer in a subject having colon cancer by utilizing the combination of (1) obtaining a T lymphocyte extracted from a colon cancer patient, expanding the T-lymphocyte in vitro by exposing it to IL-2 and extracted colon tumor antigen, and infusing the expanded autologous T lymphocytes back into the subject with (2) administering a VIP antagonist such as a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated to the subject in order to treat the colon cancer in the subject. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because administering a VIP antagonist such as a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated to a subject was known to treat colon cancer as taught by Mukherjee et al.; and because obtaining a T-lymphocyte from extracted lymph nodes, expanding the T-lymphocyte in vitro via exposure to IL-2 and a tumor antigen, and infusing the expanded autologous T-lymphocytes back into the subject was known to treat colon cancer in a subject as taught by Winqvist et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the VIP antagonist a peptide having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated of Mukherjee et al. and the expanded T lymphocytes of Winqvist et al. were administered to a subject having colon cancer to treat the colon cancer. Therefore, "it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art." (MPEP 2144.06). In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from their having been individually taught in prior art. Therefore, since each of the references teach agents that are effective in treating colon cancer, it would have been obvious to combine the two agents with the expectation that such a combination would be effective in treating colon cancer. Thus, combining them flows logically from their having been individually taught in prior art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 28-29 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Winqvist et al. WO 2010/006808 A1 published on January 21, 2010, in view of Mukherjee et al. CA Publication No. 2,197,139 A1 published on February 17, 1998 (cited in the IDS received on 4/11/23), as applied to claim 28 above, and further in view of Curtis et al., Blood 39:163-175 (1972), as applied to claim 29 herewith.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claim 28, please see discussion of Winqvist et al. and Mukherjee et al. supra.
For claim 29, with respect to where the T cell is obtained by leukapheresis;
As discussed supra for claim 28, Winqvist et al. teaches expanding tumor-reactive T-lymphocytes from sentinel lymph nodes demonstrating that it is possible to culture T-lymphocytes obtained sentinel lymph nodes (See Winqvist specification, pg. 9, 1st paragraph). These expanded tumor-reactive T-lymphocytes can treat cancer by administering an effective amount of tumor-reactive T-lymphocytes to the patient from which the sentinel nodes were removed (See Winqvist specification, pg. 9, 1st paragraph; pg. 17, 1st paragraph; pg. 25, 2nd paragraph). Winqvist et al. also teaches that the cancer to be treated includes hematological neoplasms (See Winqvist specification, pg. 22, last paragraph; pg. 25, 3rd paragraph to pg. 26, 1st paragraph).
Moreover, as discussed supra for claim 28, Mukherjee et al. teaches a pharmaceutical composition for use in killing or inhibiting multiplication of tumor cells as well as cancer cells (See Mukherjee specification, pg. 2, last paragraph) where the composition can comprise VIP1 is depicted in Table 2 as SEQ ID NO: 1 (See Mukherjee specification, pg. 8, Table 2), which is identical to instant SEQ ID NO: 9. Plus, Mukherjee et al. teaches that the cytotoxicity of each peptide analog including VIP1 was tested against a variety of cancer cell lines including human leukemia cells (See Mukherjee specification, pg. 16, 1st paragraph). As depicted in Table 8, VIP1 demonstrates a cytotoxic effects against the K562 human leukemia cell line (See Mukherjee specification, pg. 16, 1st paragraph; Table 8). Thus, the combination of Winqvist et al. and Mukherjee et al. also suggest co-administering expanded autologous T lymphocytes and a VIP antagonist to a subject in order to treat hematological neoplasms such as leukemia. However, Winqvist et al. teaches treatment of cancer by expanding T lymphocytes extracted from patient lymph nodes, and not obtained by leukapheresis.
Curtis et al. teaches the development of a safe and efficient blood cell separator technique for the removal of large numbers of peripheral blood leukocytes from normal subjects and patients with leukemia (See Curtis article, pg. 163, 1st paragraph). Preliminary studies demonstrated that more than 1011 leukocytes could be obtained from patients with chronic lymphocytic leukemia (CLL) during a single 3-4 hr procedure (See Curtis article, pg. 163, 1st paragraph). The researchers sought to investigate the effectiveness of repeated leukaphereses as remission induction and maintenance therapy for patients with CLL and to study the effects lymphocyte depletion by leukapheresis on the clinical, hematologic, immunologic and kinetic features of CLL (See Curtis article, pg. 163, 1st paragraph). To investigate such effect, Curtis et al. utilized leukapheresis therapy for 13 patients with CLL (See Curtis article, pg. 163, last paragraph). The leukaphereses were done using the IBM Blood Cell Separator, Model 2990, where blood is continuously flowed through the centrifuge at a rate of 30-50 ml/min (See Curtis article, pg. 164, 3rd paragraph). Moreover, Curtis et al. examined the in vitro lymphocyte blastogenesis in nine patients (See Curtis article, pg. 169, 2nd to 3rd paragraph) where the increase in lymphocyte blastogenesis per 106 lymphocytes during leukapheresis indicates that normal lymphocytes were being generated more rapidly than leukemic lymphocytes (See Curtis article, pg. 173, last paragraph). As such, Curtis et al. demonstrates that lymphocytes are obtained by leukapheresis in order to expand the lymphocytes. Curtis et al. concludes that the study demonstrated that leukapheresis with the Blood Cell Separator is a useful technique for the study and treatment of patients with CLL (See Curtis article, pg. 172, 3rd paragraph). Thus, the teachings of Curtis et al. suggest obtaining lymphocytes by leukapheresis which can then be used to treat CLL in a subject and/or to expand lymphocytes in vitro.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Winqvist et al. does not expressly teach where the T cell is obtained by leukapheresis as recited in instant claim 29. However, the teachings of Curtis et al. cure this deficiency by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or the use of known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant under KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to where the T cell is obtained by leukapheresis as recited in instant claim 29, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Winqvist et al. and obtain autologous T lymphocytes by leukapheresis instead of extracted lymph nodes from a patient having leukemia in order to expand autologous T lymphocytes that can then be infused back into the patient to treat the patient. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because lymphocytes from normal subjects and subjects with leukemia for expansion was known to be obtained by leukapheresis as taught by Curtis et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the T lymphocytes of Winqvist et al. were obtained from extracted patient lymph nodes and then expanded in vitro, and therefore, obtaining a leukemic patient’s T lymphocytes by leukapheresis instead of extracted lymph nodes would support the expansion of autologous T lymphocytes that are then infused back into the leukemic patient for treatment by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or the use of known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant under KSR
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicants’ Arguments
Applicants contend that the claimed invention is nonobvious because (1) the combination of Winqvist and Mukherjee fail to account for all the claim limitations (See Applicant’s Response received on 10/30/25, pg. 7); (2) an ordinary skilled artisan would not read the combination of Winqvist and Mukherjee and believe that a VIP antagonist could be used to treat leukemia let alone any other type of cancer with a reasonable expectation of success given that Table 8 of Mukherjee demonstrates that a higher concentration of the VIP antagonist resulted in lower cytotoxicity (See Applicant’s Response received on 10/30/25, pg. 7-8); and (3) the inventors provide data in an Appendix file of the MTT cytotoxicity experiments of Mukherjee for K562 leukemia cells demonstrating that VIPhyb did not have statistically significant cytotoxicity against the leukemia cell lines, and thus, a skilled artisan would not be motivated to use a VIP antagonist as a therapeutic cancer agent for leukemia (See Applicant’s Response received on 10/30/25, pg. 8-9).
Response to Arguments
Applicant's arguments filed 10/30/25 for claims 28-29, 31, and 34 have been fully considered but they are not persuasive for the following reasons.
In response to Applicants’ first and second arguments, i.e., the combination of Winqvist and Mukherjee fail to account for all the claim limitations, and an ordinary skilled artisan would not read the combination of Winqvist and Mukherjee and believe that a VIP antagonist could be used to treat leukemia let alone any other type of cancer with a reasonable expectation of success given that Table 8 of Mukherjee demonstrates that a higher concentration of the VIP antagonist resulted in lower cytotoxicity, they are found unpersuasive. It is acknowledged that every claim limitation must be addressed by a reference or combination of references in order to render a claimed invention obvious. Moreover, it is acknowledged that “[a] prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984) (See MPEP 2141). However, it is noted that the features upon which applicant relies (i.e., treatment of leukemia) is not recited in claim 28. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Here, the scope of claim 28 encompasses treatment of any cancer in a subject that has a cancer where the cancer is any cancer. As such, the scope of rejected claims is not limited to treatment of leukemia, nor is it limited to where the subject has leukemia, excluding new claim 35. As discussed in the rejection supra, since Winqvist demonstrates treatment of colon cancer in a subject by obtaining a T-lymphocyte from extracted lymph nodes, expanding the T-lymphocyte in vitro via exposure to IL-2 and a tumor antigen, and infusing the expanded autologous T-lymphocytes back into the subject, and Mukherjee demonstrates treatment of colon cancer in a subject by administering a VIP antagonist having the amino acid sequence of SEQ ID NO: 9 where X is Met and where the C-terminus is amidated, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer both the expanded T-lymphocytes and the VIP antagonist to a subject who has colon cancer in order to treat the colon cancer. Thus, contrary to Applicant’s argument, the combination of references account for all the limitations of claims 28, 31, and 34.
Additionally, pursuant to MPEP 2144.06, it states that, "[it] is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). As such, given that expanded T lymphocytes are administered to treat colon cancer and a VIP antagonist that is a peptide having a C-terminal amide alone or in combination with additional peptide analogs to form the MuJ-7 peptide analog combination is administered to treat colon cancer thereby constituting compositions each of which is taught by the prior art to be useful for the same purpose, one of ordinary skill in the art would be motivated with a reasonable expectation of success to form a third composition to be used for the very same purpose. Similarly, given that expanded γδ+ T cells are administered to treat leukemia and a VIP antagonist that is a peptide having a C-terminal amide alone or in combination with additional peptide analogs to form the MuJ-7 peptide analog combination is administered to treat leukemia thereby constituting compositions each of which is taught by the prior art to be useful for the same purpose, one of ordinary skill in the art would be motivated with a reasonable expectation of success to form a third composition to be used for the very same purpose. Therefore, the Examiner has established a prima facie case of obviousness, and Applicants have not provided evidence rebutting that such a combination would have a negative effect on each ingredient. Thus, contrary to Applicant’s argument, an ordinary skilled artisan would be motivated with a reasonable expectation of success to combine expanded T cells and a VIP antagonist that is a peptide having a C-terminal amide because both agents are known to be used for the same purpose.
Furthermore, it is noted that the level/amount of treatment is not limited in the claimed invention. As such, any amount of cytotoxicity is considered treatment. Plus, even if a low amount of cytotoxicity for a given cancer cell line is demonstrated in Mukherjee, the rejection is based on a combination of two agents known to treat the same disease, e.g., colon cancer or leukemia. An ordinary skilled artisan would expect an additive effect when the two agents are co-administered to treat the same disease. Pursuant to MPEP 716.02(a)(I), a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991). Moreover, the claimed invention does not require the expanded T-cells or VIP antagonist to be administered in any amount, let alone an effective amount. As such, the fact that Mukherjee demonstrates that a lower concentration of a VIP peptide antagonist resulted in higher cancer cytotoxicity does not preclude a finding that Mukherjee teaches administering the claimed VIP antagonist to a subject who has a cancer to treat a cancer, e.g., colon cancer or leukemia. Rather, Mukherjee demonstrates that a lower VIP antagonist concentration is useful to treat certain cancers including colon cancer and/or leukemia. Applicant has provided no evidence to the contrary (note: as discussed below, Applicant’s Exhibit A should be provided in a Declaration). Therefore, when considering the teachings of Mukherjee as a whole, an ordinary skilled artisan would combine the teachings of Winqvist/Lamb and Mukherjee to treat colon cancer/leukemia by co-administering the expanded T-cells exposed and a VIP antagonist of instant SEQ ID NO: 9 where X is M and with a C-terminal amide.
In response to Applicant’s third argument, i.e., the inventors provide data in an Appendix file of the MTT cytotoxicity experiments of Mukherjee for K562 leukemia cells demonstrating that VIPhyb did not have statistically significant cytotoxicity against the leukemia cell lines, and thus, a skilled artisan would not be motivated to use a VIP antagonist as a therapeutic cancer agent for leukemia, it is found unpersuasive. The Examiner would like to thank Applicants for providing Exhibit A on 10/30/25. However, the data should be provided in a Declaration. Pursuant to MPEP 716 and 37 CFR 1.132, [w]hen any claim of an application or a patent under reexamination is rejected or objected to, any evidence submitted to traverse the rejection or objection on a basis not otherwise provided for must be by way of an oath or declaration under this section. Further, MPEP 716.01(c) states that objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. Therefore, the additional data provided in an Appendix file is required to be provided in an Affidavit or Declaration in order to be considered since it is data not previously provided in the instant specification.
It is further noted that even if the claimed method is limited to leukemia, Mukherjee teaches that a combination therapy comprising the instant VIP antagonist was effective against leukemia. Given that the claimed invention utilizes the transitional phrase “comprising”, the combination peptide analog therapy of Mukherjee is encompassed by the claimed method.
Accordingly, the rejections of claims 28-29, 31, and 34-35 are maintained as Applicants’ arguments are found unpersuasive.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 17-18 and 20-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,850,263 B2 (Waller et al.) in view of Curtis et al., Blood 39:163-175 (1972), and Adessi et al., Curr. Med. Chem. 9:963-978 (2002). Please note that the rejection has been updated after further consideration.
‘263 claims:
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(‘263 claims 9, 12, 14, and 18 thereby corresponding to issued claims 1, 4, 6, and 10, respectively). It is noted that “augmenting” T-cell activation and ex vivo expansion is analogous to the instant “expanding a T cell” as recited in instant claim 17 where “ex vivo” is similar to “in vitro”, especially considering that the T cells to be expanded can be extracted from blood (See instant claim 18). The ‘263 claimed invention also satisfies where the T cell is exposed to a VIP antagonist as recited in instant claims 17 and 32. Plus, augmenting T-cell activation and ex vivo expansion by co-incubating human T cells, it would necessarily follow that the T cell is obtained as recited in instant claim 28. Moreover, the human T cells being activated in vitro by co-incubation with tumor associated antigens satisfies the claim limitation as recited in instant claims 21 and 31. ‘263 claim 10 reads on instant claims 26 and 28 where the in vitro expanded activated T cell is transferred into a subject with cancer.
However, ‘263 does not claim where the T cell is obtained by leukapheresis as recited in instant claim 18, and where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claim 20.
Regarding where the T cell is obtained by leukapheresis as recited in instant claim 18, ‘263 does not claim how the T cells are obtained. Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be augmented and expanded by leukapheresis.
Regarding where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 20 and 34, it is noted that ‘263 SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 9 where X is M. Adessi et al. teaches acetylation and amidation are essential to the biological stability and activity of many neuropeptides (See Adessi article, pg. 967, col. 1, 2nd paragraph). The end-protection strategy has been widely used to improve enzymatic stability in peptide drug development (See Adessi article, pg. 967, col. 1, 2nd paragraph). In fact, Adessi et al. teaches that VIP is naturally amidated at the C-terminus (See Adessi article, Table 1). Therefore, an ordinary skilled artisan would be motivated to amidate the C-terminus of ‘263 SEQ ID NO: 1 with a reasonable expectation of success in order to improve the peptide’s enzymatic stability.
Thus, the ‘263 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 17-18, 20-21, 28-29, 31-32, and 34-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,859,208 B2 (Waller et al.) in view of Winqvist et al. WO 2010/006808 A1 published on January 21, 2010, Mukherjee et al. CA Publication No. 2,197,139 A1 published on February 17, 1998 (cited in the IDS received on 4/11/23), Curtis et al., Blood 39:163-175 (1972). Please note that the rejection has been updated in light of Applicants’ amendments.
‘208 claims:
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(‘208 claims 11 and 14 thereby corresponding to issued claims 1 and 3, respectively). It is noted that “replicating” anergic T cells is analogous to the instant “expanding a T cell” as recited in instant claims 17 and 28. Moreover, it is noted that since instant claims 17 and 32 only require exposing a VIP antagonist to a T cell thereby resulting in the expansion of the T cell, ‘208’s culturing step in claim 3 necessarily constitute expanding a T cell. As such, the ‘208 claimed invention also satisfies where the T cell is exposed to a VIP antagonist as recited in instant claims 17 and 32. Plus, replicating anergic T cells in culture, it would necessarily follow that the T cell is obtained as recited in instant claim 28. ‘208 claim 3, step (iii) reads on instant claims 26 and 28 where the in vitro expanded activated T cell is transferred into a subject with cancer. ‘208 claim 14 also reads on where the cancer is leukemia as recited in instant claim 35.
However, ‘208 does not claim where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29, where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 20 and 34; where the lymphocyte is further exposed to a tumor antigen as recited in instant claims 21 and 31; and where the VIP antagonist is administered to the subject as recited in instant claims 27-28.
Regarding where the VIP antagonist is administered to the subject as recited in instant claims 27-28, please see the teachings of Mukherjee et al. supra along with the motivation to combine ‘208 and Mukherjee. Briefly, an ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer a VIP antagonist with the activated human T cells to a subject having cancer in order to treat the cancer, in particular leukemia, given that both the VIP antagonist and activated human T cells are known to treat leukemia.
Regarding where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29, ‘208 does not claim how the T cells are obtained except that they are purified in claim 3, step (i). Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be replicated by leukapheresis.
Regarding where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 20 and 34, ‘208 does not specify the species of VIP antagonist. Please see the teachings of Mukherjee et al. supra. Mukherjee demonstrates that a VIP antagonist such as instant SEQ ID NO: 9 with a C-terminal amide treats a range of cancers including leukemia. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation to utilize instant SEQ ID NO: 9 that is amidated at the C-terminus.
Regarding where the T cell is further exposed to a tumor antigen as recited in instant claims 21 and 31, please see discussion of Winqvist supra. Briefly, Winqvist et al. teaches that T lymphocytes are expanded in the presence of IL-2 and a tumor antigen obtained from the patient. Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to reactivate anergic T cells in the presence of a leukemic tumor antigen from a subject in order to treat the leukemia in the subject when the reactivated anergic leukemia specific T cells are infused back into the subject.
Thus, the ‘208 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 17-18, 20-21, 26-29, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18/047,135 (Waller et al. US Publication No. 2023/0190865 A1) in view of Curtis et al., Blood 39:163-175 (1972), and Adessi et al., Curr. Med. Chem. 9:963-978 (2002).
‘135 claims:
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623
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66
604
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(‘135 claims 1-6, 12, 15, and 21). As such, the ‘135 claimed invention reads on instant claims 17, 21, 26-28, and 31-32; more specifically, the ‘135 also claims expanding a T cell, by exposing a VIP antagonist to the T cell and treating a subject having cancer by expanding the T cell, transferring it to the subject and administering a VIP antagonist. It is noted that ‘135 claims 12-13 and 21-22 all constitute species of VIP antagonists. ‘135 further including an immune checkpoint inhibitor is encompassed by the instantly claimed invention in light of the transitional phrase “comprising”, and thus, ‘135 claims 7-11 and 16-20 are encompassed by the instantly claimed invention. Similarly, ‘135 claiming that the VIP antagonist is conjugated to a nanoparticle (See claims 14 and 23) is encompassed by the instantly claimed invention.
However, ‘135 does not claim where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29, or where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 20 and 34.
Regarding where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29, ‘135 claims that the T cells are obtained from the subject but not how they are obtained from the subject. Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be expanded by leukapheresis.
Regarding where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 20 and 34, it is noted that ‘135 SEQ ID NO: 1 in claims 12 and 21 is 100% identical to instant SEQ ID NO: 9 where X is M. Adessi et al. teaches acetylation and amidation are essential to the biological stability and activity of many neuropeptides (See Adessi article, pg. 967, col. 1, 2nd paragraph). The end-protection strategy has been widely used to improve enzymatic stability in peptide drug development (See Adessi article, pg. 967, col. 1, 2nd paragraph). In fact, Adessi et al. teaches that VIP is naturally amidated at the C-terminus (See Adessi article, Table 1). Therefore, an ordinary skilled artisan would be motivated to amidate the C-terminus of ‘263 SEQ ID NO: 1 with a reasonable expectation of success in order to improve the peptide’s enzymatic stability.
Thus, the ‘135 claimed invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection.
Claims 17-18 and 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13 and 23-27 of copending Application No. 18/510,060 (Waller et al. US Publication No. 2024/0271092 A1) in view of Curtis et al., Blood 39:163-175 (1972), and Adessi et al., Curr. Med. Chem. 9:963-978 (2002). Please note that the rejection has been updated in light of Applicants’ amendments in the ‘060 application.
‘060 claims:
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(‘060 claims 11-13). It is noted that “proliferating” T cells is analogous to the instant “expanding a T cell” as recited in instant claim 17. The ‘060 claimed invention also satisfies where the T cell is exposed to a VIP antagonist as recited in instant claim 17. ‘060 also claims where the T cells are obtained from a subject, and where the T cells are exposed to anti-CD3 antibodies as recited in instant claim 21.
However, ‘060 does not claim where the T cell is obtained by leukapheresis as recited in instant claim 18, and where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claim 20.
Regarding where the T cell is obtained by leukapheresis as recited in instant claim 18, ‘060 does not claim how the T cells are obtained other than being isolated from a subject. Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be augmented and expanded by leukapheresis.
Regarding where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claim 20, it is noted that ‘060 SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 9 where X is M. Adessi et al. teaches acetylation and amidation are essential to the biological stability and activity of many neuropeptides (See Adessi article, pg. 967, col. 1, 2nd paragraph). The end-protection strategy has been widely used to improve enzymatic stability in peptide drug development (See Adessi article, pg. 967, col. 1, 2nd paragraph). In fact, Adessi et al. teaches that VIP is naturally amidated at the C-terminus (See Adessi article, Table 1). Therefore, an ordinary skilled artisan would be motivated to amidate the C-terminus of ‘060 SEQ ID NO: 1 with a reasonable expectation of success in order to improve the peptide’s enzymatic stability.
Thus, the ‘060 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 17-18, 21, 28-29, 31-32, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 31-32, 67-68, and 72-74 of copending Application No. 18/562,111 (Waller et al. US Publication No. 2024/0247048 A1) in view of Curtis et al., Blood 39:163-175 (1972). Please note that the rejection has been updated in light of Applicants’ amendments.
‘111 claims:
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(‘111 claims 13, 31, 67, and 72). ‘111 claims 31-32 are in vitro cell culture compositions used in the instantly claimed methods. It is noted that “augmenting” T-cell activation and/or expansion is analogous to the instant “expanding a T cell” as recited in instant claims 17 and 28. The ‘111 claimed invention also satisfies where the T cell is exposed to a VIP antagonist as recited in instant claims 17 and 32. Plus, augmenting T-cell activation and expansion by mixing human T cells with a VIP antagonist, it would necessarily follow that the T cell is obtained as recited in instant claim 28. ‘111 claim 67 reads on instant claims 26 and 28 where the expanded activated T cell is transferred into a subject with cancer, ‘111 claim 50 reads on instant claim 35 where the cancer is leukemia, and ‘111 claim 14 reads on instant claims 21 and 31 where the T cells are exposed to anti-CD3 antibodies.
However, ‘111 does not claim where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29.
Regarding where the T cell is obtained by leukapheresis as recited in instant claims 18 and 29, ‘263 does not claim how the T cells are obtained. Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be augmented and expanded by leukapheresis.
Thus, the ‘111 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 17-18 and 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-15 of copending Application No. 18/889,859 (Waller et al., not yet published) in view of Curtis et al., Blood 39:163-175 (1972), and Adessi et al., Curr. Med. Chem. 9:963-978 (2002). Please note that the ‘859 pending claims is in question as the claims received on 1/8/25 do not include the amendments made on 9/19/24. Thus, this rejection will be maintained based on the amendments made on 9/19/24. Also please note that the rejection has been updated in light of Applicants’ amendments.
‘859 claims:
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(‘859 claim 13). It is noted that “augmenting” T-cell activation and/or expansion is analogous to the instant “expanding a T cell” as recited in instant claim 17. The ‘859 claimed invention also satisfies where the T cell is exposed to a VIP antagonist as recited in instant claim 17. ‘859 also reads on instant claim 31 where the T cells are exposed to anti-CD3 antibodies.
However, ‘859 does not claim where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 17 and 20, and where the T cell is obtained by leukapheresis as recited in instant claim 18.
Regarding where the VIP antagonist is a peptide having a C-terminal amide and has the amino acid sequence of SEQ ID NO: 9 where X is M as recited in instant claims 17 and 20, it is noted that ‘859 SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 9 where X is M. Adessi et al. teaches acetylation and amidation are essential to the biological stability and activity of many neuropeptides (See Adessi article, pg. 967, col. 1, 2nd paragraph). The end-protection strategy has been widely used to improve enzymatic stability in peptide drug development (See Adessi article, pg. 967, col. 1, 2nd paragraph). In fact, Adessi et al. teaches that VIP is naturally amidated at the C-terminus (See Adessi article, Table 1). Therefore, an ordinary skilled artisan would be motivated to amidate the C-terminus of ‘859 SEQ ID NO: 1 with a reasonable expectation of success in order to improve the peptide’s enzymatic stability.
Regarding where the T cell is obtained by leukapheresis as recited in instant claim 18, ‘859 does not claim how the T cells are obtained. Please see discussion of Curtis supra. Briefly, Curtis demonstrates that an ordinary skilled artisan would be well versed in obtaining T cells by leukapheresis from a normal or cancer patient where the obtained T cells can then be expanded in vitro. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to obtain the T cells to be augmented and expanded by leukapheresis.
Thus, the ‘859 claimed invention is not patentably distinct from the instantly claimed invention.
Applicants’ Arguments
Applicants respectfully request reconsideration of each of the obviousness-type double patenting rejections in light of the claim amendments (See Applicants Response received on 10/30/25, pg. 9-10).
Response to Arguments
Applicant's arguments filed 10/30/25 have been fully considered but they are not persuasive.
Applicant’s request for reconsideration is acknowledged. However, Applicants do not provide arguments to support their assertion that the rejections have been overcome in light of the instant claim amendments. Thus, the double-patenting rejections are maintained for the reasons stated forth in response to the 103 rejections supra.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached on M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654