DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31-33, 38, 46, 47, 49-51, 55, 56, 58-61, 64, 65, 69, 70 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The rejected claims cover polypeptides comprising a functional exogenous receptor, and an exogenous tumor homing peptide (THP).
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of functional exogenous receptors and exogenous tumor homing peptides, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify functional exogenous receptors and exogenous tumor homing peptides encompassed by the claims. Specifically, Applicant fails to disclose any other functional exogenous receptors and exogenous tumor homing peptides, besides those covered by the SEQ ID’s in the specification and claims, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of functional exogenous receptors and an exogenous tumor homing peptides.
With regard to the functional definition of functional exogenous receptors and exogenous tumor homing peptides, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited peptides. At best, it simply indicates that one should test an inordinate number of peptides to see if the peptides can perform the required functions, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”). In this connection, the specification contains no generic structural characteristics of those peptides which are functional exogenous receptors and an exogenous tumor homing peptides
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited functional exogenous receptors and exogenous tumor homing peptides.
Claims 38, 56 and 58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The rejected claims recite percent identities and amino acid substitutions of functional exogenous receptor SEQ ID’s. In this regard, the question is how much homology is required to claim a variant of a known sequences when the function of a peptide is recited in the claims? The Patent Trial and Appeal Board (PTAB) provides some insight on this question in Ex parte Livshits (Appeal 2013-001807; US Patent Application 11/106,455)
https://www.bradley.com/insights/publications/2016/02/how-much-homology-is-enough-under--112
In that case, the PTAB agreed with the Examiner that a PHOSITA could envision sequences that met the percent identity requirement and hybridized under the recited conditions to a known SEQ ID.
Further, the Examiner admitted that by using conservative substitutions, a PHOSITA could likely envision a DNA sequence that encoded a polypeptide having the same tertiary structure as the polypeptide encoded by SEQ ID NO:3.
However, the PTAB found there was no teaching that the conservation of structure (whether in the DNA or encoded polypeptide) would be a surrogate for conservation of the function claimed (over-expression of L-amino acids in the culture medium).
In other words, PTAB wanted some teaching as to which of the 5 percent of residues of the in the recited single domain antibody could be altered while still conserving the function of the encoded polypeptide.
Here, the specification demonstrates the recited function for the polypeptides encoded by SEQ ID NO’s, but offers no teaching as to what regions of the recited peptide are critical for conservation of the recited function and which regions could be modified.
Rather the specification leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at a the recited % identity sequence that additionally allows for recited activity.
Even if applicants attempted to use BLAST homology data to argue that a PHOSITA would be able to address the issue, but the evidence was accorded little weight and characterized as an “invitation to experiment”.
Even though the DNA/polypeptides that could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this is not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements.
Accordingly, the PHOSITA cannot determine if the peptides claimed represent a protein that accomplishes the recited function from the specification itself in order to meet the written description requirement.
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 31-33, 38, 46, 47, 49-51, 53, 55, 56, 58-61, 64, 65, 69, and 70 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.
The criteria of a “functional” exogenous receptor are undefined.
It is unclear what peptide fragments Applicant intends to cover by “variant thereof”.
The number and nature of the amino acid substitutions of the recited anti-DLL3 CAR in claim 38 are not defined.
It is unclear what combinations of peptides Applicant intends to cover (e.g., claim 46).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 31-33, 46, 47, 49-51, 59-61, 64, 65, 69, 70 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016138038 (WO 038) in view of:
CHERKASSKY, L.et al., J Clin Invest., Vol. 126, No. 8, 31 August 2016 (2016-08-31) (Cherkassky); and
LI, N.et al.; PNAS., 24 July 2017 (2017-07-24) (Li); and
LIU, G.et al. Cellular & Molecular Immunology., Vol. 18, 30 March 2021 (2021-03-30), pages 1085-1095 (Liu); and
T-cell antigen CD7 [Pan paniscus], NCBI Reference Sequence: XP_003809003.1, 248aa linear (T-cell antigen CD7); and
HOU, A.J.et al. Bioengineering & Translational Medicine., Vol. 3, 31 December 2018 (2018-12-31), pages 75-86 (Hou).
WO discloses an anti-DLL3 binding domain comprises scFv anti-DLL3 binding domain. WO 308 discloses a related anti-DLL3 CAR comprising an intracellular domain with cluster of differentiation CD3 signaling domain, or transmembrane domain comprising human CD8a hinge.
WO 038 teaches a vector which is a viral vector, a host cell that comprises DLL3 sensitized lymphocyte. The DLL3 sensitized lymphocyte comprises T cell or NK cell, where the T cell comprises CDS positive T cell, or NK cell.
The CAR in pharmaceutical composition is useful for treating cancer chosen from lung cancer, melanoma, breast cancer, prostate cancer, colon cancer, renal cell carcinoma, ovarian cancer, neuroblastoma, rhabdomyosarcoma, leukemia and lymphoma, preferably lung cancer, more preferably small cell lung cancer. Provided is a method for producing DLL3 sensitized lymphocyte, which involves transforming lymphocyte with DLL3 CAR, transducing lymphocyte with a DLL3 CAR.
Other structural components of the CAR are known:
Cherkassky teaches discloses a CAR that incorporates a human MSLN-specific scFv (30) and either CD3, CD28/CD3, or 4-1BB/CD3, signaling domains (Mz, M28z, MBBz) (see pages 3-4, figures 1-2).
Li discloses GPC2 CAR T cells kill neuroblastoma cells. CAR contains anti-GPC2 antibody single domains linked to a CD8a hinge and transmembrane region, followed by the 4-1BB costimulatory signaling moiety and the cytoplasmic component of CD3C signaling molecule. Anti-GPC2 CAR T cells demonstrate equivalent lytic capacity against LAN1 neuroblastoma cells. GPC2 CAR T cells produce significantly more IFN-y and TNF-a after exposure to IMR5 cells (see pages 5-6, 8, figure 5).
Liu discloses NGR-TNF and RGRTNF have the potential to be applied in combination therapy with CAR-T cells. NGR-TNF and RGR-TNF appear to contribute to upregulation of T cell trafficking-related adhesion molecules and chemokines in the tumor microenvironment, favoring T cell extravasation and proliferation (see page 1089).
T-cell antigen CD7 discloses the protein of T-cell antigen CD7, which includes SEQ ID NO. 14 and 13 of the invention.
Hou discloses TGF-β -responsive CAR-T cells promote anti-tumor immune function. T cells can express the TGF-β DNR (see page 79).
In view of the above, the difference between the CAR described in the applied references and the CAR covered in the rejected claims is that the applied references do not teach the instant CAR with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, based on the above, the applied references teach the structural elements of the claimed CAR with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specially, those of ordinary skill could have applied the CAR elements of the secondary references in a predictable fashion for the purposes of obtaining the recited CAR. As outlined above, WO 308 discloses an anti-DLL3 CAR. The secondary references are added for the proposition that the structural elements of the instant CAR were well within the purview of those of ordinary skill. Specifically, the secondary references teach that the particular known technique of using the instant CAR components was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the technique to a CAR, such as those described by WO 308, would have yielded predictable results. Accordingly, using the recited components for the purposes of providing a CAR would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646