DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 11/10/25, are acknowledged.
Claims 1, 15, 36, 49, 53, 58, 67, 81, 87, 90, 96 have been amended.
Claims 1, 4, 6, 14-15, 35-38, 40-41, 44, 48-50, 53, 58, 61, 63, 65-67, 69, 71-72, 77, 79, 81, 83, 87, 90, 92, and 96 are pending and are under examination.
In view of Applicant’s claim amendments, only the following rejections remain (the rejections have been reformatted to the extent necessary to address Applicant’s claim amendments).
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of dominant negative Fas polypeptides.
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 MPEP 2163.
The instant claim encompass a genus of dominant negative Fas polypeptides that are at least 80% identical to at least 99% identical to SEQ ID Nos: 16, 18, 20, 22, and 24, which would encompass modifications (addition, substitution, deletion) of any amino acid located between the signal region and cysteine rich domain 1 of human Fas of SEQ ID Nos: 16, 18, 20, 22, and 24. The state of the art is such that this region is involved in the function of dominant negative Fas polypeptides. For example, Kuehn teaches that most mutations affecting the extracellular region of Fas have no dominant negative expected effect (see abstract in particular). Likewise, US 2021/0077528 teaches that deletion of the entire region between the signal region and cysteine rich domain 1 abolishes dominant negative function (see Fig. 8, in particular). Thus, there is no art recognized correlation between the claimed structure and function. The only species of dominant negative polypeptides disclosed have SEQ ID NO: 10 with a first modification in the death inducing domain and a second modification consisting of a substitution of residue 32, a deletion of residue 32, a deletion of residues 31-32, a deletion of residues 32-33 or a deletion of residues 33-34 (i.e. SEQ ID Nos: 16, 18, 20, 22, and 24). This is not sufficiently representative of the broad genus of different modifications encompassed by the present claims. The specification provides no guidance on which other residues in the region between the signal peptide and the cysteine rich 1 domain can be modified. Thus, the specification does not disclose a correlation between structure and function.
The instant application has not provided a sufficient description showing possession of the necessary 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 genus of antibodies and inhibitors encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) 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.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
One of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Applicant argues that the amendment to claim 1 overcomes the rejection.
This is persuasive with respect to claim 1, however, as noted below, claim 14 is broader in scope than claim 1 and would encompass a genus of other mutations encompassed by polypeptides at least 80% identical to, for example, SEQ ID NO: 16, which is not adequately described for the reasons set forth above.
Claims 14, 81, 83, 87, 90, 96 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. 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 to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The instant claim encompass a genus of dominant negative Fas polypeptides that are at least 80% identical to at least 99% identical to SEQ ID Nos: 16, 18, 20, 22, and 24, which would encompass modifications (addition, substitution, deletion) of any amino acid located between the signal region and cysteine rich domain 1 of human Fas of SEQ ID Nos: 16, 18, 20, 22, and 24. The state of the art is such that this region is involved in the function of dominant negative Fas polypeptides. For example, Kuehn teaches that most mutations affecting the extracellular region of Fas have no dominant negative expected effect (see abstract in particular). Likewise, US 2021/0077528 teaches that deletion of the entire region between the signal region and cysteine rich domain 1 abolishes dominant negative function (see Fig. 8, in particular). Thus, the effect of modifications on dominant negative polypeptide function is highly unpredictable.
Claims 81, 83, 87, 90, 96 encompass methods of treating infection or neoplasms with any cell comprising said dominant negative Fas polypeptide and any antigen recognizing receptor. The claims encompass treating infection or cancer with any cell expressing any antigen recognizing receptor. For example, this would encompass a fibroblast cell that expresses receptors recognizing hormones, ligands, etc. The claims would encompass B cells, however, the role of B cells in cancer is highly unpredictable since the can have can suppress an anti-tumor immune response (see Yuen, 2016). Thus, treating or preventing cancer or infection with any cell and any antigen recognizing receptor would be highly unpredictable.
Given the unpredictability of the art and the breadth of the instant claims, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims. The specification discloses dominant negative Fas polypeptides having SEQ ID NO: 10 with a first modification in the death inducing domain and a second modification consisting of a substitution of residue 32, a deletion of residue 32, a deletion of residues 31-32, a deletion of residues 32-33 or a deletion of residues 33-34, i.e. the specification only discloses SEQ ID NO; 16, 18, 20, 22, and 24. No other guidance is provided regarding which other modifications could be tolerated. Therefore, given the unpredictability of the art and the lack of guidance provided by the instant specification, it would require undue experimentation to make and use the genus of dominant negative Fas polypeptides encompassed by the instant claim. Regarding claims 81, 83, 87, 90, and 96, while the art recognizes the use of, for example, T cells comprising a TCR or a CAR in treating infection or cancer, the instant claims are not so limited and broadly encompass a genus of cells and antigen recognizing receptors for which insufficient guidance is provided given the unpredictably in the art noted above.
Applicant argues that the amendment to claim 1 overcomes the rejection.
This is percussive with respect to claim 1, however, as noted above, claim 14 is broader in scope than claim 1 and would encompass a genus of other mutations encompassed by polypeptides at least 80% identical to, for example, SEQ ID NO: 16, which is not enabled for the reasons set forth above.
Regarding claims 81, 83, 87, 90, and 96, Applicant argues that the amendment to remove prevention from the claims overcomes the rejection.
However, the claim still encompass treating cancer or infection with any cell which is not enabled for the reasons set forth above.
The following are new grounds of rejection necessitated by Applicant’s claim amendments
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 1, 4, 6, 14-15, 35-38, 40-41, 44, 48-50, 53, 58, 61, 63, 65-67, 69, 71-72, 77, 79, 81, 83, 87, 90, 92, and 96 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 present claims recite that that dominant negative Fas comprises SEQ ID NO: 10 “and” a first modification in the death domain and a second modification as set forth in a)-f). However,. SEQ ID NO: 10 is a wild-type, full length human Fas amino sequence having 335 residues with an unmodified death domain and unmodified residues 31-33. It is not clear how the claims can require that the claimed Fas both comprises SEQ ID NO: 10 (WT) “and” also comprises certain modifications, and that the Fas functions as a dominant negative. Are the claims intending to be directed to a dominant negative Fas comprising SEQ ID NO: 10 in which certain modifications are made to SEQ ID NO: 10 (i.e. comprising SEQ ID NO: 10 with modifications)? The scope of the claims is further unclear since it is not clear what modifications are encompassed. Are the claims limited to only the first and second modifications, or would other modifications be encompassed. The scope of the claims is especially unclear, because, for example, dependent claim 14 encompass Fas polypeptides that are at least 80% identical to SEQ ID NO: 16. SEQ ID NO: 16 represents SEQ ID NO: 10 with a deletion of residue 32 (second modification) and a deletion of residues 230-314 (first modification). The specification discloses that the cytoplasmic death domain corresponds to residues 226-319 of SEQ ID NO: 10, of which only 8 residues remain in SEQ ID NO: 16 (i.e. residues 226-229 and 315-319). Therefore, arriving at a polypeptide with as little as 80% identical to SEQ ID NO: 16, as encompassed in claim 14, would necessarily require substitutions, additions, or deletions in residues outside of the death domain, or outside of the modifications specifically enumerated in a)-f). Thus, it is not clear if claim 1 is intending to encompass other modifications, or whether claim 14 is improperly broader in scope than claim 1. It is noted that claim 1 also recites a group consisting of a), b),… “or” f) which is unclear, and the use of “and” is suggested to clarify the group. Claim 1, as amended also references SEQ ID NO: 10, but then states the modifications are in death domain of “human fas” (see also claim 4, which refers to specific positions of human Fas), which is unclear (are the positions and death domain meant to be in reference to SEQ ID NO; 10, or some other human Fas)?
For the purposes of examination, claim 1 is being interpreted as requiring SEQ ID NO: 10 with only the first and second modifications, i.e. it does not allow modifications outside of the defined first and second modifications, and therefore claim 14 is improperly broader in scope than claim 1.
The following is suggested claim language for claim 1, which would clarify the claim scope and overcome the rejection under 112b:
A dominant negative Fas polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 10 with a first modification and a second modification; wherein the first modification is in a cytoplasmic death domain corresponding to residues 226-319, and wherein the second modification is selected from the group consisting of: a) a modification at position 32;b) a deletion of amino acid 32;c) a deletion of amino acids 31 and 32;d) a modification at position 33;e) a deletion of amino acids 33 and 34; and f) a point mutation S32A.
Claim 4 could be amended to recite that the first modification comprises or consists of deletion of amino acids 230-314 of SEQ ID NO: 10, for example.
The proposed amendment to claim 1 would be interpreted as a dominant negative Fas comprising SEQ ID NO: 10, with only the first and second modifications, wherein the second modification is one of the options enumerated in options a)-f), and the first modification is within the death domain corresponding to 226-319 of SEQ ID NO: 10. For example, this would encompass SEQ ID NO: 10 with S32A and a deletion of 223-319 of SEQ ID NO: 10, or said S32A with any other modification within residues 226-319 of SEQ ID NO 10. However, other modifications outside of the death domain corresponding to residues 226-319 in SEQ ID NO: 10 and/or outside of the modifications enumerated in a)-f) would not be encompassed.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 encompasses dominant negative Fas polypeptides comprising or consisting of an amino acid sequence at least about 80% identical to SEQ ID NO: 16, 18, 20, 22, and 24, which is broader in scope than claim 1, from which the claim depends. For example, SEQ ID NO: 16 represents SEQ ID NO: 10 with a deletion of residue 32 (second modification) and a deletion of residues 230-314 (first modification). The specification discloses that the cytoplasmic death domain corresponds to residues 226-319 of SEQ ID NO: 10, of which only 8 residues remain in SEQ ID NO: 16 (i.e. residues 226-229 and 315-319). Therefore, arriving at a polypeptide with as little as 80% identical to SEQ ID NO: 16, as encompassed in claim 14, would necessarily require substitutions, additions, or deletions in residues outside of the death domain, or outside of the modifications specifically enumerated in a)-f).
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644