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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 3, 5-7, 11, 27, 30, 31, and 33-38 and species: lysine and IgG in the reply filed 08/11/2025 is acknowledged.
Claims 7, 18 and 39 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 08/11/2025.
Claims 1, 3, 5-6, 11, 23-24, 26-27, 30-31, and 33-38 are now under consideration in the instant Office Action.
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 1, 3, 5-6, 11, 23-24, 26-27, 30-31, and 33-38 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.
In instant claim 1, it is not clear whether “a variant thereof” is referring to a variant of a viral component (i.e., “a variant of a component of a respiratory syncytial virus”) or a variant of a respiratory syncytial virus (i.e., “a variant of a respiratory syncytial virus”). The dependent claims use the same language and are thus indefinite for the same reason.
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 1, 3, 5-6, 11, 23-24, 26-27, 30-31, and 33-38 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 instant claims encompass a chimeric protein comprising: (a) a target-binding moiety that specifically binds to a component of a respiratory syncytial virus (RSV) or a variant thereof; and (b) a mucoadhesive peptide fragment, comprising about 5 to about 50 positively charged amino acid residues, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa.
Claims 1, 3, 5-6, 11, 23-24, 26-27, 30-31, and 33-38 do not require any structural requirements for claimed chimeric protein. While claim 11 further limit the targeting moiety as being an antibody moiety or an antigen binding fragment thereof that specifically binds the component of the RSV or variant, the instant claims still have no structural requirement for the antibody and the mucoadhesive peptide fragment. Thus, the claims encompass a genus of chimeric proteins that comprise a target-binding moiety and a mucoadhesive peptide fragment without any structural requirements.
The specification teaches an antibody designated the full length clone #26 human IgG that comprises a specific heavy and light chain sequences, wherein the full-length clone #26 human IgG antibody was fused to a polylysine peptides having 6-30 contiguous residues, (example 6, [0564] and table 11). The specification teaches that the lysine peptides are attached to the C-terminus of the heavy chain, (see SEQ ID NOs: 97, 98, 131 and 132). The specification fails to disclose any other chimeric proteins. Additionally, this antibody binds to αSARS-CoV-2, which is not the antigen that the instant claims are drawn to. The specification demonstrates that modification of the full length clone #26 human IgG antibodies with polylysine peptides increased binding to mucin attached to plates and detected with HRP-conjugated anti-human Fc antibodies, (figure 27). The specification further teaches modified full length clone #26 human IgG antibodies in nasal spray buffer” or “NS buffer” which prevented SARS CoV-2 pseudovirus infection in huACE2-expressing mice, (see figure 28). It is noted that the specification also discloses other SARS-CoV2 antibodies directed against spike protein at pages 58-62. The specification broadly teaches that “mucoadhesive peptide fragment” refers to a peptide that carries one or more positive charges and is capable of interacting with a mucosa (page 25, [0102]; see also pages 67-77).
While the specification is permitted to list multiple potential embodiments that Applicant has identified and described, the instantly recited embodiment from the claims must also appear in the disclosure in order for the disclosure to properly support the claimed invention. As noted above, the instant claims do not list sequence(s) for the instantly claimed antibody that is claimed to bind to respiratory syncytial virus (RSV) or a variant thereof. Instant claim 24 broadens the scope even further, by reciting that the plurality of chimeric proteins must be different from each other without properly claiming or describing what one complete embodiment of the invention would be.
The instant specification cites numerous embodiments of chimeric antigen proteins with mucoadhesive peptide fragments; however, these embodiment are drawn to antigen-binding region sequences that are specific to SARS-CoV-2. One of ordinary skill in the art would recognize that SARS-CoV-2 and RSV are distinct and discrete antibodies with different viral entry mechanisms. As such, these terms cannot be used interchangeably, nor would one necessarily read on the other. The instant claims are drawn to a chimeric antigen protein whose target-binding moiety specifically binds to RSV; however, the only references to an invention binding RSV in the instant disclosure are purely exemplary, with no structural detail, antibody, or embodiment to show that Applicant is in possession of the recited invention, see paragraphs [0021], [0145], [0148]. Key descriptions of the invention as possessed in paragraphs [0048], [0058-0063], [0097-0099], [0146-0148], [0440-0454], [0489-0491] show that Applicant has described the invention as binding to SARS-CoV-2 and used as part of nasal administrations. As such, Applicant has not shown possession of the instant invention as claimed.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, structure/function correlation, methods of making the product, or any combination thereof. In this case, the only factors present in the claims are the recitation of a chimeric protein that comprises a target-binding moiety to RSV and a mucoadhesive peptide fragment, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa. There is not even identification of any particular portion of a structure that must be conserved for the required biological function. The specification only describes SARS-CoV-2 antibodies directed against spike protein and modified full-length clone #26 human IgG antibodies that comprise polylysine residues at the C-terminus of the heavy chain. However, the disclosure of one modified antibody to a different antigen than is claimed is not representative of the genus of chimeric proteins that comprise a target-binding moiety that binds to RSV and a mucoadhesive peptide fragment, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa, as encompassed by the instant claims.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of recited chimeric proteins that comprise a target-binding moiety that binds to RSV and a mucoadhesive peptide fragment, wherein the mucoadhesive peptide fragment comprises about 5 to about 50 positively charged amino acid residues (and facilitates attachment of the chimeric protein to the mucosa).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states 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). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of chimeric proteins (and nucleic acids encoding such), and therefore conception is not achieved until reduction to practice has occurred, 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 of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claims 1, 3, 5-6, 11, 23-24, 26-27, 30-31, and 33-38 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 a chimeric protein comprising (a) an antibody that binds SARS-CoV-2 spike protein; and a mucoadhesive peptide fragment, wherein said mucoadhesive peptide fragment is a polylysine peptide having 5-50 contiguous lysine, does not provide enablement for a chimeric protein comprising: (a) a target-binding moiety that specifically binds to a component of a respiratory syncytial virus (RSV) or a variant thereof; and (b) a mucoadhesive peptide fragment, comprising about 5 to about 50 positively charged amino acid residues, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The instant claims encompass a chimeric protein comprising (a) a target-binding moiety that specifically binds to a component of a respiratory syncytial virus (RSV) or a variant thereof; and (b) a mucoadhesive peptide fragment, comprising about 5 to about 50 positively charged amino acid residues, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa.
The specification teaches an antibody that blocks binding of human ACE2 to SARS-CoV-2 spike protein, with said antibody designated as full length clone #26 human IgG.
The specification teaches that the full length clone #26 human IgG antibody is fused at the C-terminus to a peptide having 6-30 contiguous lysine, histidine or arginine residues, (see paragraphs [0565-0566], SEQ ID NOs: 96, 97, 98, 131, 132). The specification teaches that each #26-hIgG-6K molecule has four polypeptide chains, including two copies of SEQ ID NO: 96 and two copies of SEQ ID NO: 97, (see paragraph [0565]). The specification demonstrates that modification of the #26-hIgG1 antibodies with polylysine peptides increased binding to mucin attached to plates and detected with HRP-conjugated anti-human Fc antibodies, (figure 27). The specification further teaches said modified full length clone #26 human IgG antibodies in nasal spray buffer” or “NS buffer” prevented SARS CoV-2 pseudovirus infection in huACE2-expressing mice, (see figure 28). It is noted that the specification also discloses other SARS-CoV2 antibodies directed against spike protein at pages 58-62. The specification teaches that “mucoadhesive peptide fragment” refers to a peptide that carries one or more positive charges and is capable of interacting with a mucosa (page 25, [0102]; see also pages 67-77).
However, the instant claims are broadly directed to a chimeric protein that comprises a target-binding moiety that specifically binds to a component RSV or a variant thereof and a mucoadhesive peptide fragment, comprising about 5 to about 50 positively charged amino acid residues, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to the mucosa. Instant claim 11 recites that the target-binding moiety is an antibody. However, there are no working examples in the instant specification that indicate all possible chimeric proteins that comprise all possible target-binding moieties that bind to RSV and all possible mucoadhesive peptide fragments of 5-50 positively charged amino acids that are recited in the claims are functional, let alone able to bind to the claimed RSV antigen or variant thereof. A large quantity of experimentation would be required of the skilled artisan to determine such. Such experimentation is considered undue.
Furthermore, regarding antibodies that may bind a target or pathogenic component, the state of the art is such that it is well established that the antigen binding site of antibody molecules consists of hypervariable regions that are complimentary to the structure of the cognate epitope. These regions, which are the greatest contributors to antibody variation and specificity, are widely referred to as complimentary-determining regions (CDRs). There are three CDRs near the terminal ends of each heavy and light chain variable domain for a total of 12 CDRs, and these CDR regions contain the majority of the amino acid residues that initiate contact between the antibody molecule and the cognate antigen epitope (Goldsby et al. 2003, in instant PTO-892). Functional antigen binding sites are formed when heavy and light chain variable domains assume a specific confirmation. In addition to the traditional binding model involving all 12 CDR regions, it is now understood that smaller molecules are capable of antigen binding and recognition. Multiple groups have developed functional antigen binding molecules, called scFv fragments, which consist of a single heavy chain domain linked to a single light chain variable domain. See Huston et al. 1988 (in instant PTO-892) and Bird et al. 1988 (in instant PTO-892). Other groups have developed antigen binding molecules consisting of a single variable domain. For example, Ward et al. 1989 (in instant PTO-892) discovered that a single, isolated heavy chain variable domain was capable of binding lysozyme. In addition to proper order and confirmation, the sequence of each CDR is also critical for antibody-epitope interactions. It has been demonstrated that the substitution of a single CDR amino acid can completely abrogate antigen binding specificity. Rudikoff et al. 1982 (in instant PTO-892) showed that the substitution of glutamic acid to alanine at position 35 of S107, a phosphocholine-binding myeloma protein, resulted in the loss of antigen binding activity. Thus, the scope of the claim is extremely broad relative to the guidance and direction provided in the specification. As a result, due to the considerable breadth of the claims, one possessing ordinary skill in the art would have to engage in an excessive quantity of experimentation in order to make or use the invention based on the content of the disclosure.
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability. In the antibody field, it is well-known that altering amino acid sequences in CDRs yields unpredictable results. As stated above, single changes in CDR amino acid sequences may greatly enhance epitope-antibody interactions or lead to a total loss of antigen recognition. Accordingly, the level of predictability for the claimed invention is deemed low as there are no structural details provided in the instant claims and there are no working examples in the specification which support the breadth of RSV binding chimeric proteins with mucoadhesive peptides that are claimed.
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. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004). Due to the high level of unpredictability in the art, the skilled artisan would need significant guidance to assemble chimeric proteins that comprise a genus of target-binding moieties that specifically bind to RSV or a variant thereof; and unknown mucoadhesive peptide fragments, comprising about 5 to about 50 positively charged amino acid residues, that would enable the mucoadhesive peptide fragment to facilitate attachment of the chimeric protein to the mucosa. As discussed above, Applicant has only disclosed a chimeric protein comprising an antibody that binds SARS-CoV-2 spike protein (such as the amino acid sequence of SEQ ID NOs: 96, 97, 98, 131, 132, (see paragraph [0156], example 6, [0564-0567]; pages 58-62). For a claimed genus, representative examples together with a statement applicable to the genus as a whole will ordinarily be sufficient if one skilled in the art (in view of level of skill, state of the art and the information in the specification) would expect the claimed genus could be used in that manner without undue experimentation. Proof of enablement will be required for other members of the claimed genus only where adequate reasons are advanced by the examiner to establish that a person skilled in the art could not use the genus as a whole without undue experimentation. Given the lack of disclosed guidance in predicting all the encompassed “targeting moieties to RSV and mucoadhesive peptide fragments” and the general unpredictability in the art, the specification does not enable the skilled artisan how to practice the claimed genus without undue experimentation.
Therefore, the instant specification is only enabling for a chimeric protein comprising (a) an antibody that binds SARS-CoV-2 spike protein; and a mucoadhesive peptide fragment, wherein said mucoadhesive peptide fragment is a polylysine peptide having 5-50 contiguous lysine residues, respectively.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675