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 .
Claims 1-20 are pending and are under examination.
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 4-11, 14-20 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.
Regarding claims 4-5, the phrase "preferably" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Furthermore, claim 5 recites in lines 1-2 that the nucleic acid encodes the antibody or antigen binding fragment of claim 1, and said antibody or antigen binding fragment in claim 1 comprises both a heavy and light chain variable region. However, the claim further recites that the nucleic acid molecule “preferably” encodes the heavy chain or the light chain variable regions. Therefore, it is not clear whether the claim requires a nucleic acid encoding both heavy and light chain variable regions, or whether the claim would encompass a nucleic acid encoding only a heavy chain variable region or only a light chain variable region of said antibody, as recited after the preferably limitation. For the purposes of examination, claim 5 is being interpreted as requiring a nucleic encoding the antibody or antibody fragment of claim 1, i.e. a nucleic acid encoding both the heavy and light chain variable regions specifically recited in claim 1.
Claim 5 also recites the limitation "the corresponding nucleotide sequence" in lines 5 and 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 is indefinite in the recitation of a biomaterial that is an “expression product, a suspension or a supernatant of the above (1)”. It is not clear what the biomaterial is. For example, host cells express various products, and contain various things in a suspension, and it is not clear what biomaterial is required.
Regarding claim 7, 9, 11, 14-15, 19-20 the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 11, 19-20 are also indefinite in the recitation that the additional cancer agent includes “but is not limited to” the recited elements for similar reasons, i.e. it is unclear whether the recited elements are part of the claimed invention and/or what other alternatives are intended to be encompassed by the claim.
Regarding claims 9, 11, 14-15, 19-20, the phrase "such as" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 8 recites the limitation "the host cell" comprising “the nucleic acid molecule” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 10, 16-18 are indefinite in the recitation of a method for blocking the binding of SIRPa to CD40 comprising “using the antibody or antigen binding fragment thereof of claim 1”. The claim does not specify any actual steps for how the antibody is used which is ambiguous and renders the claims indefinite since it is not clear what uses would be encompassed. See MPEP 2173.05(q), attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b), second paragraph.
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.
Claims 1, 3-11, 14-20 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 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 anti-SIRPa antibody or antigen binding fragments thereof.
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 claims are directed to a genus of anti-SIRPa antibodies, or antigen binding fragments thereof, comprising a genus of CDRH1-3 and CDRL1-3 selected from those recited in claim 1. This represents a large genus of distinct antibodies that can be made by mixing matching the different individual CDR sequences recited in claim 1, in any combination.
The state of the art is such that the CDRs of an antibody are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). See also Chen which teaches that a single amino acid change in a CDR2 can abolish antigen binding, and that increasing the number of mutations dramatically influences loss of binding (See page 858, in particular).
The specification does not provide a correlation between structure and function nor does it disclose a representative number of species The specification discloses 4 species of anti-SIRPa antibodies, wherein the antibodies comprise the specific HCDR1-3 and LCDR1-3 pairings specified in claim 2. This is not sufficiently representative of the genus of different CDRs pairing encompassed by claim 1. The CDR regions from the 4 disclosed antibodies are completely distinct. For example, CDRHI of SEQ ID NO: 3 is DYYIQ and CDRH1 of SEQ ID NO: 13 is SHGVH. CDRH2 of SEQ ID NO: 4 is WIDPENGDTKYAPKFQG, and CDRH2 of SEQ ID NO: 14 is VIWSDGSTTYNSTLK.
Swapping or mixing and matching the distinct CDRs with different amino acid sequences to create a genus of different antibodies would be highly unpredictable. No guidance is provided regarding which combinations of CDRs could be employed, other than the specific combinations in claim 2.
The application at best describes a roadmap for producing candidate antibodies and then determining which actually function as claimed. See Novozymes A/S v. DuPont Nutrition Biosciences. 107 USPQ2d 1457 (Fed. Cir. 2013). Thus, 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.
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 binding molecules. 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).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning – i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3.
Thus, 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.
Claims 1, 3-11, 14-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
An anti-SIRPa antibody or an antigen-binding fragment thereof, comprising: a heavy chain variable region comprising three CDRs, VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region comprising three CDRs, VL CDR1, VL CDR2 and VL CDR3, wherein
the amino acid sequence of the VH CDR1 is set forth in SEQ ID NO: 3; the amino acid sequence of the VH CDR2 is set forth in SEQ ID NO: 4; the amino acid sequence of the VH CDR3 is set forth in SEQ ID NO: 5; the amino acid sequence of the VL CDR1 is set forth in SEQ ID NO: 8; the amino acid sequence of the VL CDR2 is set forth in SEQ ID NO: 9; and the amino acid sequence of the VL CDR3 is set forth in SEQ ID NO: 10; or,
the amino acid sequence of the VH CDR1 is set forth in SEQ ID NO: 13; the amino acid sequence of the VH CDR2 is set forth in SEQ ID NO: 14; the amino acid sequence of the VH CDR3 is set forth in SEQ ID NO: 15; the amino acid sequence of the VL CDR1 is set forth in SEQ ID NO: 18; the amino acid sequence of the VL CDR2 is set forth in SEQ ID NO: 19; and the amino acid sequence of the VL CDR3 is set forth in SEQ ID NO: 20; or,
the amino acid sequence of the VH CDR1 is set forth in SEQ ID NO: 23; the amino acid sequence of the VH CDR2 is set forth in SEQ ID NO: 24; the amino acid sequence of the VH CDR3 is set forth in SEQ ID NO: 25; the amino acid sequence of the VL CDR1 is set forth in SEQ ID NO: 28; the amino acid sequence of the VL CDR2 is set forth in SEQ ID NO: 29; and the amino acid sequence of the VL CDR3 is set forth in SEQ ID NO: 30; or,
the amino acid sequence of the VH CDR1 is set forth in SEQ ID NO: 33; the amino acid sequence of the VH CDR2 is set forth in SEQ ID NO: 34; the amino acid sequence of the VH CDR3 is set forth in SEQ ID NO: 35; the amino acid sequence of the VL CDR1 is set forth in SEQ ID NO: 38; the amino acid sequence of the VL CDR2 is set forth in SEQ ID NO: 39; and the amino acid sequence of the VL CDR3 is set forth in SEQ ID NO: 40.;
does not reasonably provide enablement for:
An anti-SIRPa antibody or an antigen-binding fragment thereof, comprising: a heavy chain variable region comprising three CDRs, VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region comprising three CDRs, VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 3, 13, 23 or 33, the VH CDR2 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 4, 14, 24 or 34, the VH CDR3 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 5, 15, 25 or 35, the VL CDR1 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 8, 18, 28 or 38, the VL CDR2 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 9, 19, 29 or 39, and the VL CDR3 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 10, 20, 30 or 40.
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 claims are directed to a genus of anti-SIRPa antibodies, or antigen binding fragments thereof, comprising a genus of CDRH1-3 and CDRL1-3 selected from those recited in claim 1. This represents a large genus of distinct antibodies that can be made by mixing matching the different individual CDR sequences recited in claim 1, in any combination.
The state of the art is such that the CDRs of an antibody are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). See also Chen which teaches that a single amino acid change in a CDR2 can abolish antigen binding, and that increasing the number of mutations dramatically influences loss of binding (See page 858, in particular).
The specification discloses 4 species of anti-SIRPa antibodies, wherein the antibodies comprise the specific HCDR1-3 and LCDR1-3 pairings specified in claim 2. This is not sufficiently representative of the genus of different CDRs pairing encompassed by claim 1. The CDR regions from the 4 disclosed antibodies are completely distinct. For example, CDRH1 of SEQ ID NO: 3 is DYYIQ and CDRH1 of SEQ ID NO: 13 is SHGVH. CDRH2 of SEQ ID NO: 4 is WIDPENGDTKYAPKFQG, and CDRH2 of SEQ ID NO: 14 is VIWSDGSTTYNSTLK. Swapping or mixing and matching the CDRs to create a genus of different antibodies would be highly unpredictable. No guidance is provided regarding which combinations of CDRs could be employed, other than the specific combinations in claim 2.
Thus, based on the unpredictability of the art, the lack of guidance provided by the instant specification, and the breadth of the claims, it would require undue experimentation to make and use the genus of antibodies as broadly claimed.
Claims 12-13 are allowed. Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The claims are free of the prior art since the prior art does not teach or suggest an anti-SIRPa antibodies having VH CDR1-3 and VL CDR1-3 comprising the CDR sequences recited in the present claims.
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, Misook Yu can be reached on 571-272-0839. 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