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 .
The preliminary amendment filed 2/22/2024 is acknowledged. Claims 3, 5-6, 8, 11, 13, 15-23, 26-28, 30, and 37-38 are amended. Claims 4, 7, 9-10, 12, 14, 24-25, 29, 32-34, and 40-44 are cancelled. Claims 1-3, 5-6, 8, 11, 13, 15-23, 26-28, 30-31, and 35-39 are pending and are currently under examination.
Information Disclosure Statement
The information disclosure statement filed on 2/22/2024 has been considered. A signed copy is enclosed.
Specification
The use of the terms ALHYDROGEL (page 20), SEPHAROSE (page 70), SUPEROSE (page 71), SUPERDEX (page 71), and TWEEN (pages 74-75), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
It is noted that the cited occurrences of improper use are only exemplary and applicant should review the specification to correct any other use of trademarks.
Claim Rejections - 35 USC § 112
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, 5-6, 8, 11, 13, 17-23, 26-27, 30-31, and 35-39 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.
The instant claims are drawn to fusion polypeptides and to functional fragments and variants thereof comprising SARS CoV-2 spike protein RBD dimers fused to NTD. Some claims specify amino acid sequences, however, these include functional fragments and variants and, where specific amino acid sequences are required, the claims only require the sequence for that specific portion of the fusion polypeptide. The only function recited in the claims is in claim 39, requiring the composition to be a vaccine.
The claims encompass an essentially unlimited number of polypeptides since they include variants (with no limit on the number or kind of changes for most claims), as well as a very large number of functional fragments. The specification does not define what function a functional fragment is supposed to have. The specification discloses a particular mRNA construct that is capable of immunizing mice against SARS CoV-2. There is no description in the specification of any fragments that have any given function and there is no description of the numerous variants that could be made by changing the sequences of the recited domains.
Therefore, the claimed polypeptides have no disclosed correlation between their structure and function. The claims require some function but the specification provides no guidance regarding which variants or fragments are capable of the required function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. 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.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al. (Science, 1990, 247:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (column 1, page 1306). Bowie et al. further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Therefore, the full breadth of the claims does not meet the written description provision of 35 USC 112, first paragraph. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision. (See page 1115).
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 1-3, 5-6, 8, 11, 13, 15-23, 26-28, 30-31, and 35-39 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 pre-AIA the applicant regards as the invention. Claims not specifically mentioned below are included because they contain the issue of the parent claim.
Claim 1 is indefinite because of the way it refers to functional fragments or variants thereof. The claim requires a fusion polypeptide or functional fragment or variant thereof comprising at least one RBD dimer fused to an NTD. However, claims 2-3 provide a sequence for the dimer but then state that the RBD dimer can be a functional fragment or variant of the sequence. Therefore, it appears that the dependent claims only require a variant or fragment of the RBD dimer while the parent claim requires an actual RBD dimer. However, the parent claim also refers to functional fragments and variants. Thus, it is not clear what is actually required and what can or cannot be a functional fragment or variant of what
Claim 15 is rendered indefinite by the phrase “wherein the amino acid residues at positions 211-213 and 432-436 are small neutral or small non-polar amino acid residues.” The claim language makes it seems as if there is a choice to be made for these residues. However, SEQ ID NO:1 specifies what these residues are so there is no choice to be made and the resides cannot be one or the other of the recited limitations.
Claim 16 is rendered indefinite by the phrase “wherein the amino acid residues at positions 220 and 440-441 are small neutral or small non-polar amino acid residues.” The claim language makes it seems as if there is a choice to be made for these residues. However, SEQ ID NO:21 specifies what these residues are so there is no choice to be made and the resides cannot be one or the other of the recited limitations.
Claims 1-3, 17, 23, 31, and 35-36 are indefinite because it is not clear what limitations the term “functional fragment” engenders. The term implies that there is a function that is necessary, but no function is recited in the claims so it is not clear what would serve as a “functional fragment”.
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.
Claim 13 is rejected under 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 13 requires that the RBD dimer and NTD are fused to each other by a non-immunogenic amino acid linker. However, this is already required by the parent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 17, 20, and 35-36 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Stewart-Jones et al (WO2021/159040, published 8/12/2021; IDS filed 2/22/2024).
The instant claims are drawn to fusion polypeptides or functional fragments of variatns thereof. Claim 17 requires, in order from the N terminus to the C terminus, a portion of SARS-CoV-2 S protein binding domain, a portion of SARS-CoV-2 S protein binding domain, and a portion of SARS-CoV-2 S N terminal domain. Claims 35 and 36 list specific sequences with specific amino acid positions, but then require only a functional fragment or variant thereof.
Stewart-Jones et al disclose SARS-CoV-2 vaccines comprising fusion polypeptides with various combinations of linkers and domains. These include a SARS-CoV-2 spike protein RBD domain linked to an N terminal domain. As claim 17 only requires a portion of RBD, the RBD disclosed by Stewart-Jones et al meets the limitations of the claims since any given first section of the RBD is a portion of RBD followed by any given second section serves as the second portion of RBD. With regard to claims 35 and 36, the fusion polypeptide disclosed is a variant of the sequences recited in the claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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