DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-20 are pending in this application.
This application is listed in the instant application as a continuation of U.S. application 17/047,059 filed 10/12/2020, now U.S. Patent 11,390,659, which is a 371 filing of PCT/CN2019/082408 filed 4/12/2019 which claims priority to PCT/CN2018/082947 filed 4/13/2018. The certified copy of the priority document in English that accompanies the parent application is not accompanied by a full set of pages.
Sequences above SEQ ID NO:81 are not presented in the priority document and therefore for art purposes, the claims so directed to sequences corresponding to SEQ ID NO:81-207 are afforded a filing date of 10/12/2020.
Information Disclosure Statement
An IDS filed 1/27/2021 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action.
Several documents under Foreign Patent Documents have not been considered and have been crossed out as these publications are not in English nor are they accompanied by an explanation of the relevance, “as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, unless a complete translation is provided (See MPEP § 609.05).
Claim Objections
Claim 5 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 2. Claim 10 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. Claim 5 and 10 repeat the information in claims 2 and 7 and add that the epitope that is bound to is an epitope in SEQ ID NO:85. This is already required in claim 1 from which each of the claims depend. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 8, 9, 11, 13, 15 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre- AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre- AIA 35 U.S.C. 112, the applicant), regards as the invention. This rejection is necessitated by applicants' amendment. Claim 1 establishes a TCR comprising one of 5 TCRα chains and one of 5 TCRβ chains. Subsequent reference to "the TCRα" or "the TCRβ" chain of claim 1 is unclear as to which is being referenced. Hence, there is a lack of clear antecedent basis.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 1-20 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating a non-human subject with cervical cancer comprising HPV E7, the method comprising intravenously administering to the subject a pharmaceutical composition comprising autologous activated T-cells, wherein the TCR binds to an epitope of HPV18-E7 comprising an amino acid sequence of SEQ ID NO: 85, and wherein the TCR is selected from the group consisting of the following TCRs: (a) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 274, a CDR2 comprising the amino acid sequence of SEQ ID NO: 275, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 58; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 276, a CDR2 comprising the amino acid sequence of SEQ ID NO: 277, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 61; wherein the TCRa. chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 226, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 224
(b) a TCR comprising a TCRa chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 278, a CDR2 comprising the amino acid sequence of SEQ ID NO: 279, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 70; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 280, a CDR2 comprising the amino acid sequence of SEQ ID NO: 281, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 73; wherein the TCRa. chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 226, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 224; wherein the TCRa chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 234, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 232
(c) a TCR comprising a TCRa chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 282, a CDR2 comprising the amino acid sequence of SEQ ID NO: 283, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 76; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 284, a CDR2 comprising the amino acid sequence of SEQ ID NO: 285, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 79; wherein the TCRa. chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 218, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 216,
(d) a TCR comprising a TCRa chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 286, a CDR2 comprising the amino acid sequence of SEQ ID NO: 287, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 87; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 288, a CDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 90; wherein the TCRa chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 246, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 244
and
(e) a TCR comprising a TCRa chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 290, a CDR2 comprising the amino acid sequence of SEQ ID NO: 291, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 93; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 292, a CDR2 comprising the amino acid sequence of SEQ ID NO: 293, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 96; wherein the TCRa chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 230, and the TCRb chain comprises a variable region comprising the amino acid sequence of SEQ ID NO: 228
does not reasonably provide enablement for any other embodiment. The specification does not enable any person skilled in the art to which it. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
Nature of invention. The nature of the invention is directed to T cell therapy to treat cancer.
Scope of the invention. The scope of the invention is mostly narrow in that the immune effector cells must (a) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 274, a CDR2 comprising the amino acid sequence of SEQ ID NO: 275, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 58; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 276, a CDR2 comprising the amino acid sequence of SEQ ID NO: 277, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 61; (b) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 278, a CDR2 comprising the amino acid sequence of SEQ ID NO: 279, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 70; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 280, a CDR2 comprising the amino acid sequence of SEQ ID NO: 281, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 73; (c) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 282, a CDR2 comprising the amino acid sequence of SEQ ID NO: 283, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 76; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 284, a CDR2 comprising the amino acid sequence of SEQ ID NO: 285, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 79; (d) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 286, a CDR2 comprising the amino acid sequence of SEQ ID NO: 287, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 87; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 288, a CDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 90; and (e) a TCR comprising a TCRa. chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 290, a CDR2 comprising the amino acid sequence of SEQ ID NO: 291, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 93; and a TCRb chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 292, a CDR2 comprising the amino acid sequence of SEQ ID NO: 293, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 96; but it is also quite broad in that the cancer is selected from any cancer.
Number of working examples and guidance. The specification teaches identification of tumor associated peptides by analysis of tissue samples of tumors. In Example 1, a patient with cervical cancer received MASCT treatment and following demonstrated enhanced T cell response to the cervical carcinoma antigen peptide pool and core tumor specific antigen peptides. ECT (Emission Computed Tomography) demonstrated reduced metastasis and prevented tumor progression. A patient specific peptide pool was developed. In Example 2, 12 pairs of TCR and TCR paired genes were identified for next generation sequencing. This led to tumor-antigen specific T cells which were used to prepare a population of tumor antigen specific T cells with enhanced percentages of RGS5 specific T cells and HPV18-E7 specific TCRs.
The same experimental approach was performed with a patient with metastatic lung cancer. The method used a two round amplification process for tumor specific T cell amplification from the patient. Hence the method demonstrates that T cell specific preparations.
State of the art. Regarding administration, there is no evidence that any means of administering the cells other than by vascular or systemic administration, is possible. Regarding modes of administration, adverse effects as well as off target side effects and lack of concentration of the T cells have hampered use of immunotherapy (see Murthy, JCNI, 2017, page 2, col 2- page 3, col 1).
As well, the cancer does not correlate with the TCR but is any cancer. Buonaguro et al (Clinical and Vaccine Immunology, 2010) demonstrates a number of cautions in the field (page 23, col 1),
In this context, considering the disappointing results up to now, the quest for specific and selective tumor antigens for developing tumor-specific cancer vaccines, optimal delivery systems (i.e., dendritic cell [DC]-based vaccines), adjuvants, and strategies to overcome immune tolerance and regulatory T (Treg) cell responses is the main goal for several research groups and leading health care companies.
This is further complicated as the art recognizes that tumor specific T cells have shown reduced efficacy against solid tumors (see Durgeau et al, Cancer Immunotherapy, 2018, page 6, col 2 and Cadhila et al, European Oncology and Haematology, 2017). At issue is the tumor microenvironment which is hostile for T cells which creates an unpredictable art. Many attempts at adjuvants, tissue modifiers and cytokines have been tested but clinically T cell administration to solid tumors has not been successful (see e.g. Durgeau et al, page 8 and Cadhila et al entire document).
5) Unpredictability of the art. The method steps of claims 1-20 are quite broad leading to a lack of predictability. This is complicated by the lack of guidance for treatment methods in the specification. The disclosure only teaches in vitro analysis. First, the claims simply require intravenous administering the engineered immune cells comprising the TCR. However, the disclosure teaches use of T cells and the art teaches that the cells must be autologous. Secondly, the patient is any with any cancer and yet the art teaches that cell therapy is limited in the target cancer it can treat. Finally, the claims lack a projected outcome.
The art of cancer therapy is part of the physiological arts as is the art of vaccination by T cell. The physiological art is recognized as unpredictable. (MPEP 2164.03.) In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.
This is complicated by the lack of art accepted in vivo results in solid tumors which applicants provide no evidence of overcoming the art recognized obstacles thereof. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971). This is complicated by the unpredictability of correlation based upon in vitro analysis.
The issue of ‘correlation’ is related to the issue of the presence or absence of working examples. ‘Correlation’ as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a ‘working example’ if that example ‘correlates’ with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute ‘working examples’.
Translation of the use of tumor antigens have several hurdles to overcome (see Hollingsworth and Jansen (Vaccines, 2019, page 2, col 1).
Several hurdles are associated with developing vaccines against TAAs. First, as self-antigens, B cells and T cells that strongly recognize these antigens may have been removed from the immune repertoire by central and peripheral tolerance. Thus, a cancer vaccine must “break tolerance” by stimulating the low affinity or rare TAA reactive T cells that remain.24 Strong adjuvants, co-stimulators, and repeated vaccination have been used to amplify the activation and expansion of self-antigen-reactive T cells,25 and this is particularly important for low-affinity T cells. Even with such enhancements, for many TAA-directed vaccine clinical trials the immune response, while detectable, does not appear to be strong enough to achieve significant efficacy.
A second challenge for targeting TAAs is that even if they are overexpressed on tumor cells, normal cell expression may lead to collateral damage. Although cancer vaccines have had acceptable tolerability so far, in many cases the vaccine was not efficacious and thus may have lacked potency. However, on-target off-tumor toxicity has been observed in clinical studies testing other therapies targeting TAAs.
The instant case does not demonstrate the translation of the identification of a peptide to human therapy (Hollingsworth and Jansen, page 5, col 1).
Many peptide vaccine clinical trials have been conducted with demonstration of immune responses, yet significant clinical benefit has been elusive.
In addition, short peptides do not activate CD4 helper T cells, which are necessary for full activation of cytotoxic T lymphocytes (CTLs).
Human testing is not to be required. Rather the rejection establishes that for a number of reasons, the specification does not enable the full breadth of the claims. T In short, results can be confirmed in animals and in vitro assays when they are enabled. In this case when the art is unpredictable and applicants claim outcomes that have been proven not to work in humans, more is necessary.
Finally, while this examination is for a single species, it is noted that claims drawn to TCRand with limited homology (80% in this case) lack adequate written description. What is missing to use known methods and functional assays is characterization of the family of sequences. The claims are distinctly drawn to a genus of known and unknown species of proteins. Applicants do not provide the requisite identification parameters to know which of the numerous proteins claimed meet the functional properties of required by the specification. What is required is that the structural/functional nexus be known. Applicant’s arguments have not addressed this issue as set forth in the rejection. The predictability of identifying nucleic acid variants is not a high art and requires as set forth above that the molecule be characterized. In the face of missing structural requirements, there exist large genus of sequences comprising any number of non-functionally as well as functionally active sequences that do not affect the instant invention.
For written description, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
The specification does not detail structural domains but single amino acid sequence without identification of the genus. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
6) Amount of Experimentation Required. The enablement of the instant invention has been assessed in light of the specification and the prior art available at the time of filing. It has been established by legal decision that a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion. Tossing out the germ of an idea does not constitute an enabling disclosure. While every aspect of a generic claim need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable the skilled artisan to understand and carry out the invention. It is true that a specification need not disclose what is well known in the art. However, that general, oft-repeated statement is merely a rule of supplementation, not a substitute for a basic enabling disclosure. It means that the omission of minor details does not cause a specification to fail to meet the enablement requirement under 35 USC 112, first paragraph. When there is no disclosure of the specific starting materials or conditions under which the process can be carried out, there is a failure to meet the enablement requirement. See Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (Fed. Cir. 1997).
The issues that make the invention non-enabled are the following. First, one cannot extrapolate the surprising teaching of the specification to the claimed invention because the in vitro data presented is not commensurate with the claimed targets. The MPEP is clear.
The issue of ‘correlation’ is related to the issue of the presence or absence of working examples. ‘Correlation’ as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a ‘working example’ if that example ‘correlates’ with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute ‘working examples’.
And, in this case, the in vitro results are not reflective of tumors in subjects. As an initial issue, it is well established in the art that there is no correlation between in vitro results and cancer therapy. But more directly, the in vitro results are much narrower than the claimed goals.
As well, the evidence provided in the specification is insufficient to enable the treatment of the broad group of cancers because of the unpredictability of the art. The rejection establishes that the art of T cell therapy is a highly unpredictable art with a number of unresolved obstacles. Hollingsworth teaches that the art of T cell therapy is faced with a number of obstacles prime amongst is tumor selectivity as well as erratic effectiveness and immunosuppressive effects of the subject. The art is clear that the cancer and TCR specificity must be correlative. And the art teaches that the tumor microenvironment blocks entry of and effect of T cells. Hence, the efficacy of CTL against solid tumors is limited. There has only been efficacy shown in melanoma. Hollingsworth,
Adoptive T cell therapies have also produced remarkable responses, in particular CAR-T therapy in acute lymphocytic leukemia and TIL therapy in melanoma. These breakthroughs have proven the feasibility and efficacy of cancer immunotherapies, and opened new paths to develop other new medicines. However, many patients do not respond to current immunotherapies, and most that do eventually relapse; in addition, many patients experience adverse effects with current therapies. Therapeutic: cancer vaccines offer an attractive alternative immunotherapy because of their potential safety, specificity, and long-lasting response—perhaps even cures—due to stimulation of immune memory. Unfortunately, many previous attempts to develop effective therapeutic cancer vaccines yielded disappointing results. Lessons learned from these failed attempts are now allowing cancer vaccine research to turn the corner and begin to achieve some promising clinical results. The key lessons driving this progress emanate from three areas: the need for multiple, immunogenic antigens; the importance of highly potent vaccine vectors; and a growing understanding of how to quell tumor-mediated immunosuppression.
What is known is that solid tumors in humans are refractory to this therapy (Durgeau, page 6, col 2.
While ACT of tumor-specific T cells holds promise for melanoma treatment, significant challenges remain in clinical translation to other solid tumors. This can be explained by the observation that some tumors, referred to as “immune-desert tumors” or “cold tumors,” are rarely infiltrated by T cells, and TIL often display an exhausted state acquired in the tumor microenvironment.
Most recently, Cadilha affirms that the therapy is not predictable,
However, current approaches are not specific, limiting both their activity and their safety. A more tailored way of using the therapeutic potential of T cells is adoptive T cell therapy, which encompasses ex vivo T cell manipulation and reinfusion to patients suffering from cancer. In haematologic malignancies such as acute lymphatic leukaemia of the B cell lineage, T cells modified with a chimeric antigen receptor against the B cell lineage antigen CD19 induce remissions in a high proportion of patients. In contrast, patients suffering from advanced solid tumours have shown little benefit from cell-based approaches. This is partly due to limited access of T cells to the tumour tissue, consequently restricting T cell activity.
TIL, TCR-transduced T cell and CAR-transduced T cell therapies are under clinical investigation for cancer treatment. Current clinical trials will decide on their approval for certain indications. While some of these strategies are likely to be approved in defined indications such as ALL, the majority of tumour patients will not benefit from this approach in the near future. A major reason, especially for solid tumours, is the limited access of adoptively administered T cells to the tumour tissue. Strategies such as T cell engineering with chemokine receptors need to be tested in clinical protocols based on preclinical evidence. However, it needs to be stressed, that those cells that eventually reach the tumour, still need to recognise the tumour cell adequately and prevail over
immunosuppression. This will require both advanced T cell engineering and combination with other immune and nonimmune therapies.
The results presented in the art do not necessarily preclude Applicant's hypothesis, they certainly fail to support it. Consequently, the prior art (and post-filing art) when combined with the lack of any disclosed direct experimental test of Applicant's hypothesis, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed invention would succeed. There is no evidence that the specification offers a solution to the problem set forth in the specification. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art.
MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one skilled in the art. The large breadth of the claims exacerbates this unpredictability. The specification ultimately teaches that there is potential to treat a human subject with patient derived set of TCRs. However, as set forth above, there are issues with delivery methods as well as the breadth of the T cells claimed.
Given the lack of guidance in the specification, the large and diverse group of treatments recited and the highly unpredictable nature of the art, it is concluded that a person of skill in the art would have had to conduct undue experimentation in order to practice the claimed invention. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. The more that is known in the prior art about the nature of the invention, how to make and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order for it to be enabling. In this case, the art is immature and more generically the physiological arts are recognized as unpredictable (see MPEP 2164.03).
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-20 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-28 of U.S. Patent 11,390,659 (the instant case is listed as continuation of the parent application 17/047,059).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-28 of U.S. Patent 11,390,659. That is, the cited claims of U.S. Patent 11,390,659 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, application U.S. Patent 11,390,659 is drawn to methods of treatment of a specific cancer wherein the instant claims are drawn to treatment of any cancer.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 11,390,659, then two different assignees would hold a patent to the claimed invention of U.S. Patent 11,390,659, and thus improperly there would be possible harassment by multiple assignees.
Claims 1-20 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-18 of copending Application No. 17/843,920.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are related as a method of use of the products recited in claims 1-18 of copending Application No. 17/843,920. The safe harbor for non-statutory double patenting only applies for applications filed as divisional applications. Because all sets of claims are drawn to the capsid of AdY25 and methods of use and vectors comprising, the claims are related under the non-statutory double patenting statute. Neither copending Application No. 17/843,920 and the instant application were filed as divisionals.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the copending Application No. 17/843,920, then two different assignees would hold a patent to the claimed invention of copending Application No. 17/843,920, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
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/MARIA MARVICH/Primary Examiner, Art Unit 1633
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