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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
No IDS is currently on the record.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show the features in details as described in the specification at page 13, para. 3, page 14, para. 2, page 15, para. 4. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d).
Specifically, the details of Fig. 13, Fig. 15B, Fig. 21A, and Fig. 21B contain features that cannot be sufficiently distinguished over the background.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the term “Alexa Fluor”, on page 13, para. 3, page 14, para. 2, page 15, para. 4, page 20, para. 7, page 21, para. 2, page 23, para. 5 which is a trade name or a mark used in commerce, has been noted in this application. The term 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.
The use of the term “Carl Zeiss”, on page 13, para. 3, page 20, para. 7, page 21, para. 2, page 23, para. 5, which is a trade name or a mark used in commerce, has been noted in this application. The term 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.
The use of the term “Oxoid”, on page 14, para. 2, page 21, para. 4, page 24, para. 2 which is a trade name or a mark used in commerce, has been noted in this application. The term 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.
The use of the term “QIAamp”, on page 22, para. 1, which is a trade name or a mark used in commerce, has been noted in this application. The term 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.
Claim Interpretation
In claim 1, “A peptide selected from the group consisting of:…” is interpreted to mean “A peptide consisting of a sequence selected from the group consist of:…”. In the specification, specific sequences are used in the examples and no elaboration or theory on other variants is provided.
Claim Objections
Claim 7 is objected to because of the following informalities. The term “transmembrane” lacks an article, such as “the”, before said term appears in the sentence. Furthermore, the term “domain” should appear after the term “transmembrane” for clarity. Appropriate correction is required.
Claim 8 is objected to because of the following informalities. The phrase “is a protein of SEQ ID NO: 1, …” is more accurately rephrased as “is a peptide of SEQ ID NO: 1, …”. Additionally, claim 8 recites “wherein the coronavirus-derived spike protein or spike protein fragment thereof is a protein of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8 or a fragment thereof.” This potentially refers to a fragment of a fragment. In light of the specification, references to these subfragments should be removed. Appropriate correction is required.
Claims 12 is objected to under 37 CFR 1.75 as being a substantial duplicates of claim 6. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 14 is objected to because of the following informalities. The phrase “is a protein of SEQ ID NO: 1, …” is more accurately rephrased as “is a peptide of SEQ ID NO: 1, …”. Additionally, claim 8 recites “wherein the coronavirus-derived spike protein or spike protein fragment thereof is a protein of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8 or a fragment thereof.” This potentially refers to a fragment of a fragment. In light of the specification, references to these subfragments should be removed. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6-9, and 12-15 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to a natural phenomenon without significantly more.
Regarding claim 1, claim 1 recites SEQ ID NO: 1, a fragment of the MERS-CoV spike protein, aligned with the C-terminus of the wild type MERS-CoV spike protein below (Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013).
0
EMBOSS_001 1301 LGFIAGLVALALCVFFILCCTGCGTNCMGKLKCNRCCDRYEEYDLEPHKV 1350
||||||||||||||||
EMBOSS_001 1 --------------------TGCGTNCMGKLKCNRC-------------- 16
EMBOSS_001 1351 HVH 1353
EMBOSS_001 17 --- 16
Also, claim 1 recites SEQ ID NO: 6, aligned with the C-terminus of wild type SARS-CoV2 spike protein below (Uniprot Accession number P0DTC2, accessed 10/8/2025, uploaded 4/22/2020).
EMBOSS_001 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250
|||||||||||||||||
EMBOSS_001 1 ---------------------------------LCCMTSCCSCLKGCCSC 17
EMBOSS_001 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273
|||||||||||||||||||||||
EMBOSS_001 18 GSCCKFDEDDSEPVLKGVKLHYT 40
Also, claim 1 recites SEQ ID NO: 8, aligned with the C-terminus of wild type HCoV-OC43 spike protein below (Uniprot Accession number P36334, accessed 10/8/2025, uploaded 6/1/1994).
EMBOSS_001 1301 WLLICLAGVAMLVLLFFICCCTGCGTSCFKKCGGCCDDYTGYQELVIKTS 1350
|||||||||||||||||||||||||||||||
EMBOSS_001 1 -------------------CCTGCGTSCFKKCGGCCDDYTGYQELVIKTS 31
EMBOSS_001 1351 HDD 1353
|||
EMBOSS_001 32 HDD 34
MPEP 2106.04(II)(C) states: “Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.” These sequences are identical to the wild-type sequences, and therefore are not markedly different.
This judicial exception is not integrated into a practical application because claim 1 is a composition claim, not a method claim. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only element claimed is the composition itself. Consequently, claim 1 is rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 recites SEQ ID NO: 4, a fragment of the MERS-CoV spike protein, aligned with the C-terminus of the wild type MERS-CoV spike protein below (Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013).
EMBOSS_001 1301 LGFIAGLVALALCVFFILCCTGCGTNCMGKLKCNRCCDRYEEYDLEPHKV 1350
||||||||||||||||||||||||||||||
EMBOSS_001 1 --------------------TGCGTNCMGKLKCNRCCDRYEEYDLEPHKV 30
EMBOSS_001 1351 HVH 1353
|||
EMBOSS_001 31 HVH 33
MPEP 2106.04(II)(C) states: “Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.” This sequence is identical to the wild-type sequence, and therefore is not markedly different.
This judicial exception is not integrated into a practical application because claim 2 is a composition claim, not a method claim. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only element claimed is the composition itself. Consequently, claim 2 is rejected.
Regarding claim 3, claim 1 is rejected as described above. Claim 3 further defines the functional language of claim 1. Claim 3 does not recite a practical application or additional elements; therefore, claim 3 is rejected.
Regarding claim 6, claim 6 recites a composition comprising a coronavirus-derived spike protein or a spike protein fragment thereof as an active ingredient. The previously rejected spike protein sequences SEQ ID NOs: 1, 4, 6, and 8 are all coronavirus-derived spike protein fragments. Furthermore, the sequences of coronavirus spike proteins were known in the art before the effective filing date of the claimed invention (Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013) (Uniprot Accession number P0DTC2, accessed 10/8/2025, uploaded 4/22/2020) (Uniprot Accession number P36334, accessed 10/8/2025, uploaded 6/1/1994).
MPEP 2106.04(II)(C) states: “Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.” These sequences are identical to the wild-type sequences, and therefore are not markedly different.
This judicial exception is not integrated into a practical application because claim 6 is a composition claim, not a method claim. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only element claimed is the composition itself. Consequently, claim 6 is rejected.
Regarding claim 7, claim 6 is rejected as described above. Claim 7 further recites the case where the spike protein fragment is derived from a domain after the transmembrane domain of the spike protein.
The domains of MERS-CoV are shown below:
PNG
media_image1.png
143
1420
media_image1.png
Greyscale
(Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013).
SEQ ID NO: 1 begins at residue 1320, and therefore is in the topological domain, which comes after the transmembrane domain. Claim 7 is rejected.
Regarding claim 8, claim 6 is rejected as described above. Claim 8 further recites the case wherein the spike protein fragment is SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8 or a fragment thereof. SEQ ID NOs: 1, 4, 6, and 8 are addressed above in claim 6. Consequently, claim 8 is rejected.
Regarding claim 9, claim 6 is rejected as described above. Claim 9 further defines the coronavirus of claim 6. The sequences of MERS-CoV, SARS-CoV2, and HCoV-OC43 were known in the art as described above. Claim 9 does not recite a practical application or additional elements; therefore, claim 9 is rejected.
Regarding claim 12, claim 12 recites a composition comprising a coronavirus-derived spike protein or a spike protein fragment thereof as an active ingredient. The previously rejected spike protein sequences SEQ ID NOs: 1, 4, 6, and 8 are all coronavirus-derived spike protein fragments. Furthermore, the sequences of coronavirus spike proteins were known in the art before the effective filing date of the claimed invention (Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013) (Uniprot Accession number P0DTC2, accessed 10/8/2025, uploaded 4/22/2020) (Uniprot Accession number P36334, accessed 10/8/2025, uploaded 6/1/1994).
MPEP 2106.04(II)(C) states: “Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.” These sequences are identical to the wild-type sequences, and therefore are not markedly different.
This judicial exception is not integrated into a practical application because claim 6 is a composition claim, not a method claim. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only element claimed is the composition itself. Consequently, claim 12 is rejected.
Regarding claim 13, claim 12 is rejected as described above. Claim 13 further recites the case where the spike protein fragment is derived from a domain after the transmembrane domain of the spike protein.
The domains of MERS-CoV are shown below:
PNG
media_image1.png
143
1420
media_image1.png
Greyscale
(Uniprot Accession number K9N5Q8, accessed 10/8/2025, uploaded 3/6/2013).
SEQ ID NO: 1 begins at residue 1320, and therefore is in the topological domain, which comes after the transmembrane domain. Claim 13 is rejected.
Regarding claim 14, claim 12 is rejected as described above. Claim 14 further recites the case wherein the spike protein fragment is SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8 or a fragment thereof. SEQ ID NOs: 1, 4, 6, and 8 are addressed above in claim 12. Consequently, claim 14 is rejected.
Regarding claim 15, claim 12 is rejected as described above. Claim 15 further defines the coronavirus of claim 12. The sequences of MERS-CoV, SARS-CoV2, and HCoV-OC43 were known in the art as described above. Claim 15 does not recite a practical application or additional elements; therefore, claim 15 is rejected.
Claim Rejections - 35 USC § 112
Claim 1 is 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 claim 1, claim1 recites the limitation "the coronavirus" in line 2. There is insufficient antecedent basis for this limitation in the claim. Furthermore, the three sequences reference by claim 1 each correspond to a different strain of coronavirus, namely, MERS-CoV, SARS-CoV2, and HCoV-OC43. Consequently, the phrase “the coronavirus” is indefinite because it is unclear to which coronavirus the phrase is referring. If it is meant to be the coronavirus from which each of the claimed peptides is derived, this relationship should be made clear. Claim 1 is rejected.
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 2 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.
Regarding claim 2, claim 2 depends from claim 1. Claim 1 recites a peptide selected from a group of three sequences. Claim 2 recites the peptide of claim 1, wherein the peptide is a sequence not recited by claim 1, nor is a subsequence of any of the sequences of claim 1. Therefore, this claim introduces a new peptide and therefore broadens claim 1 in scope. Claim is 2 rejected.
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.
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 1-2, 4-8, 10-14, and 16-17 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.
Regarding claim 1, claim 1 recites the functional limitation “that binds to the coronavirus N-protein”. No particular coronavirus is specified, so this genus encompasses any possible coronavirus.
Masters discloses a range of more than 20 coronaviruses known in the art. (Masters, Paul S. Advances in virus research 66: 193-292 (2006), page 197, Table I). These viruses possess different sequences and have evolved to infect different hosts.
In this case, 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Applicant discloses the fragments of spike proteins of three coronavirus variants: MERS-CoV, SARS-CoV2, and HCoV-OC43. These spike proteins are shown to illicit desirable effects when introduced into infected cells.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ 45.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
In the instant case, three species members have been disclosed. At the time the invention was made, the level of skill for preparing peptides and then selecting those peptides with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structures provided by the three provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what peptide with a particular set of properties would look like structurally beyond the provided repeats. However, subsequences of the disclosed members have been claimed as well as variations that necessarily modify the repeats in undisclosed ways.
The specification is focused on spike fragments of a given coronavirus that binds to the N protein of that same given coronavirus that illicit a desirable response. No common structural features are disclosed that would a priori allow a person of ordinary skill in the art to expect cross-virus binding capabilities. Since only three species of peptides are taught that illicit a desirable response in cells infected with viruses of the claimed genus above and only then to the viruses of from which said peptides are derived, the instant claims above fail the written description requirement. A representative number of species has not been taught to describe this genus.
A single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of polypeptide design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 1. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 1 is rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 recites an additional peptide sequence that binds to MERS-CoV N protein. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 2 is rejected.
Regarding claim 4, claim 1 is rejected as described above. Claim 4 recites the case wherein the peptide of claim 1 further comprises a peptide for cell penetration. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 4 is rejected.
Regarding claim 5, claim 4 is rejected as described above. Claim 5 further defines the cell penetrating peptides of claim 4. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 5 is rejected.
Regarding claim 6, claim 6 encompasses the same genus of coronaviruses as claim 1. Furthermore, the spike proteins recited are not as well-defined as they are in claim 1. The specification discloses a total of seven peptides derived from three different coronaviruses. Claim 6 is recites a coronavirus spike protein or spike protein fragment thereof with no limitations on the source coronavirus. Furthermore, the specification does not disclose the usage of any full proteins, only peptide fragments.
Because of the discrepancies in genus sizes of both the coronaviruses claimed and the protein/peptides claimed and the examples of the specification, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 6. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 6 is rejected.
Regarding claim 7, claim 6 is rejected as described above. Claim 7 recites a limitation on the location of a potential spike fragment, but does not alter any of the genus sizes involved. Consequently, claim 7 is rejected.
Regarding claim 8, claim 6 is rejected as described above. Claim 8 resolves the issue of genus size for the protein/peptide fragments by reciting explicit sequences. However, the genus of the coronavirus is not altered effectively resulting in the same scope as claim 1 described above.
Claim 8 is therefore rejected.
Regarding claim 10, claim 6 is rejected as described above. Claim 10 recites the case wherein the peptide of claim 6 further comprises a peptide for cell penetration. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 10 is rejected.
Regarding claim 11, claim 10 is rejected as described above. Claim 11 further defines the cell penetrating peptides of claim 10. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 11 is rejected.
Regarding claim 12, claim 12 encompasses the same genus of coronaviruses as claim 1. Furthermore, the spike proteins recited are not as well-defined as they are in claim 1. The specification discloses a total of seven peptides derived from three different coronaviruses. Claim 12 is recites a coronavirus spike protein or spike protein fragment thereof with no limitations on the source coronavirus. Furthermore, the specification does not disclose the usage of any full proteins, only peptide fragments.
Because of the discrepancies in genus sizes of both the coronaviruses claimed and the protein/peptides claimed and the examples of the specification, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 12. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 12 is rejected.
Regarding claim 13, claim 12 is rejected as described above. Claim 13 recites a limitation on the location of a potential spike fragment, but does not alter any of the genus sizes involved. Consequently, claim 13 is rejected.
Regarding claim 14, claim 12 is rejected as described above. Claim 14 resolves the issue of genus size for the protein/peptide fragments by reciting explicit sequences. However, the genus of the coronavirus is not altered effectively resulting in the same scope as claim 1 described above. Claim 14 is therefore rejected.
Regarding claim 16, claim 12 is rejected as described above. Claim 16 recites the case wherein the peptide of claim 12 further comprises a peptide for cell penetration. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 16 is rejected.
Regarding claim 17, claim 16 is rejected as described above. Claim 17 further defines the cell penetrating peptides of claim 16. This does not change the number of species possessed nor reduce the genus size of claimed coronaviruses and therefore claim 17 is rejected.
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 1-17 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 SEQ ID NO: 1 and SEQ ID NO: 4 binding to MERS-CoV N protein, SEQ ID NO: 6 and SEQ ID NO: 7 binding to SARS-CoV2 N protein, and SEQ ID NO: 8 binding to HCoV-OC43 N protein, does not reasonably provide enablement for the claimed peptides to bind to any possible coronavirus N protein. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
MPEP 2164.01(a) states: “In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is ‘reasonable’ or is ‘undue.’”
These factors include, but are not limited to:
The breadth of the claims;
Claim 1 is not broad in terms of the peptide claimed, but it is extremely broad in terms of which coronavirus N protein is being bound. This is the general case for the application, but claim 6 is even broader because it fails to specify a particular protein/peptide as the binder molecule.
The nature of the invention;
The invention is a series of coronavirus spike protein derived peptides that bind to the N protein of each respective coronavirus.
The state of the prior art;
Coronaviruses were well-known in the art before the effective filing date of the claimed invention (Maier, et al. Coronaviruses: methods and protocols : 1-23 (2015)). Specifically, the N proteins of various coronaviruses were known to possess limited sequence conservation (Chang, et al. Antiviral research 103: 39-50 (2014), Page 42, Fig. 2). One example of this: “The SARS-CoV N protein is a 46 kDa phosphoprotein of 422 amino acids, sharing 20–30% sequence identity with the N proteins of other coronaviruses” (Chang et al., page 41, col. 2, para. 3).
The spike proteins of various coronaviruses also possess limited identity. The spike protein of SARS-CoV2 is aligned against SARS-CoV below:
# Aligned_sequences: 2
# 1: EMBOSS_001
# 2: EMBOSS_001
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 1277
# Identity: 975/1277 (76.4%)
# Similarity: 1111/1277 (87.0%)
# Gaps: 26/1277 ( 2.0%)
# Score: 5230.0
#
#
#=======================================
EMBOSS_001 1 MFVFLVLLPLVS-SQCVNLTTRTQL-PPAYT--NSFTRGVYYPDKVFRSS 46
||:||:.|.|.| |.....||...: .|.|| .|..|||||||::|||.
EMBOSS_001 1 MFIFLLFLTLTSGSDLDRCTTFDDVQAPNYTQHTSSMRGVYYPDEIFRSD 50
EMBOSS_001 47 VLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTE 96
.|:.||||||||:||||.||.| |.| |.|||:||.||:|||:||
EMBOSS_001 51 TLYLTQDLFLPFYSNVTGFHTI-----NHT--FGNPVIPFKDGIYFAATE 93
EMBOSS_001 97 KSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYH 146
|||::|||:||:|:::|:||::|:||:|||||:.|.|:.|::||..|
EMBOSS_001 94 KSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFFAV--- 140
EMBOSS_001 147 KNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKN 196
:.....::...::.:|.||||||:|..|.:|:..|.||||:||||||||
EMBOSS_001 141 -SKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVFKN 189
EMBOSS_001 197 IDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHR 246
.||:..:|..:.||::|||||.||:.|:|:..||:|||||.|:.:|
EMBOSS_001 190 KDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAIL---- 235
EMBOSS_001 247 SYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL 296
:..:|.... |...||||:||||:|.||:|||:|||||||||||:.:||
EMBOSS_001 236 TAFSPAQDI--WGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPL 283
EMBOSS_001 297 SETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATR 346
:|.||::|||.::|||||||||||.|:..:|||||||||||||||||||:
EMBOSS_001 284 AELKCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATK 333
EMBOSS_001 347 FASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVY 396
|.|||||.||:||||||||||||||..||||||||||.||||||||:|||
EMBOSS_001 334 FPSVYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVY 383
EMBOSS_001 397 ADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVG 446
|||||::||:||||||||||.||||||||||||.|||:|||:.|:|:...
EMBOSS_001 384 ADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATST 433
EMBOSS_001 447 GNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYG 496
|||||.||..|...|:|||||||...:.....||. ....|||:||..||
EMBOSS_001 434 GNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCT-PPALNCYWPLNDYG 482
EMBOSS_001 497 FQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGL 546
|..|.|:|||||||||||||||:|||||||||.||:|:||:|||||||||
EMBOSS_001 483 FYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNFNGL 532
EMBOSS_001 547 TGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVS 596
|||||||.|:|:|.||||||||::|.||:||||:|.|||||:||||||||
EMBOSS_001 533 TGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFGGVS 582
EMBOSS_001 597 VITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTR 646
|||||||.|::|||||||||||:|..|||||||||.||:||||:|||||:
EMBOSS_001 583 VITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNNVFQTQ 632
EMBOSS_001 647 AGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYT 696
||||||||||:.||||||||||||||||.|.: ..||.:.:||:|||
EMBOSS_001 633 AGCLIGAEHVDTSYECDIPIGAGICASYHTVS----LLRSTSQKSIVAYT 678
EMBOSS_001 697 MSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDS 746
|||||::|:|||||:|||||||:||:|||::||||.||||||.|||||||
EMBOSS_001 679 MSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGDS 728
EMBOSS_001 747 TECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKD 796
|||:|||||||||||||||||:|||.|||:||:||||||||:||||.:|.
EMBOSS_001 729 TECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPTLKY 778
EMBOSS_001 797 FGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAA 846
|||||||||||||.||:||||||||||||||||||||:||||:|||||.|
EMBOSS_001 779 FGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLGDINA 828
EMBOSS_001 847 RDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQI 896
|||||||||||||||||||||:|||.||:||::||.|:||||||||||||
EMBOSS_001 829 RDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGAGAALQI 878
EMBOSS_001 897 PFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALG 946
|||||||||||||||||||||||||.||||||.||.:||:||::|::|||
EMBOSS_001 879 PFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLTTTSTALG 928
EMBOSS_001 947 KLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRL 996
||||||||||||||||||||||||||||||||||||||||||||||||||
EMBOSS_001 929 KLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRL 978
EMBOSS_001 997 ITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKG 1046
||||||||||||||||||||||||||||||||||||||||||||||||||
EMBOSS_001 979 ITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKG 1028
EMBOSS_001 1047 YHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFV 1096
||||||||:||||||||||||||:||:||||||||||:|||:||||||||
EMBOSS_001 1029 YHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEGKAYFPREGVFV 1078
EMBOSS_001 1097 SNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELD 1146
.|||.||:|||||:.|||||||||||||||||||||:|||||||||||||
EMBOSS_001 1079 FNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNTVYDPLQPELD 1128
EMBOSS_001 1147 SFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES 1196
||||||||||||||||||||||||||||||||||||||||||||||||||
EMBOSS_001 1129 SFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES 1178
EMBOSS_001 1197 LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKG 1246
|||||||||||||||||||:||||||||||||||||:|||||||||||||
EMBOSS_001 1179 LIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKG 1228
EMBOSS_001 1247 CCSCGSCCKFDEDDSEPVLKGVKLHYT 1273
.||||||||||||||||||||||||||
EMBOSS_001 1229 ACSCGSCCKFDEDDSEPVLKGVKLHYT 1255
(Uniprot Accession number P0DTC2, accessed 10/8/2025, uploaded 4/22/2020 and Uniprot Accession number P59594, accessed 10/8/2025, uploaded 4/23/2003)
The level of one of ordinary skill;
The level of one of ordinary skill in the art is relatively high. Typically, the level would be at least a master’s level education and likely a PhD level education.
The level of predictability in the art;
Generally speaking, the level of predictability in the area of protein engineering is low. As described above, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
The amount of direction provided by the inventor and the existence of working examples; and The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant discloses the fragments of spike proteins of three coronavirus variants: MERS-CoV, SARS-CoV2, and HCoV-OC43. These spike proteins are shown to illicit desirable effects when introduced into infected cells. Notably, the spike protein fragments are used to bind specifically to the N protein of the same coronavirus variant from which the spike protein originates.
Regarding claim 1, the sequences recited by this claim are enabled for the N protein variants from which they are derived, as shown by the data disclosed by the current application. However, as shown above, the sequences of the N proteins of various coronaviruses do not possess a high degree of identity. Determination of the ability of any given spike protein fragment’s ability to bind to the open-ended number of coronaviruses would require undue experimentation due to the number of coronaviruses and the divergent nature of their N protein sequences. Consequently, claim 1 is rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 further recites SEQ ID NO: 4, which is enabled for the MERS-CoV, but not an unlimited range of coronaviruses. Consequently, claim 2 is rejected.
Regarding claim 3, claim 1 is rejected as described above. Claim 3 further specifies various coronavirus variants. This claim is close to being enabled; however, the current claim language indicates that any peptide of claim 1 could bind to any coronavirus variant. Due to sequence diverge and limited assays, the specification only enables each spike fragment for the corresponding coronavirus against which it originated and was tested. Consequently, claim 3 is rejected.
Regarding claim 4, claim 1 is rejected as described above. The addition of a cell penetrating peptide may certainly improve cellular uptake, but does not further enable N protein binding in and of itself. Therefore, for the reasons listed in claim 1, claim 4 is rejected.
Regarding claim 5, claim 4 is rejected as described above. Claim 5 further defines the cell penetrating peptide of claim 4. This does not further enable N protein. Therefore, claim 5 is rejected.
Regarding claim 6, claim 6 is broader than claim 1. Claim 6 does not recite a specific spike protein fragment nor a specific coronavirus. Claim 6 is not enabled for the same reasons as claim 1, but also because without a more specific spike protein fragment, testing the huge amount of potential fragments of various spike proteins would require undue experimentation. Therefore, claim 6 is rejected.
Regarding claim 7, claim 6 is rejected as described above. Claim 7 provides some guidance on the spike protein fragment, but no target protein is specified nor does this address the issue of the identity of the coronavirus from claim 6. Therefore, claim 7 is rejected.
Regarding claim 8, claim 6 is rejected as described above. The sequences recited by this claim are enabled for the N protein variants from which they are derived, as shown by the data disclosed by the current application. However, as shown above, the sequences of the N proteins of various coronaviruses do not possess a high degree of identity. Determination of the ability of any given spike protein fragment’s ability to bind to the open-ended number of coronaviruses would require undue experimentation due to the number of coronaviruses and the divergent nature of their N protein sequences. Consequently, claim 8 is rejected.
Regarding claim 9, claim 6 is rejected as described above. Claim 9 further specifies various coronavirus variants. However, claim 6 recites an open-ended number of spike protein fragments. Determination of which spike protein fragments bind to the recited coronavirus variants would require undue experimentation. Consequently, claim 9 is rejected.
Regarding claim 10, claim 6 is rejected as described above. The addition of a cell penetrating peptide may certainly improve cellular uptake, but does not further enable N protein binding in and of itself. Therefore, for the reasons listed in claim 6, claim 10 is rejected.
Regarding claim 11, claim 10 is rejected as described above. Claim 11 further defines the cell penetrating peptide of claim 10. This does not further enable N protein binding. Therefore, claim 11 is rejected.
Regarding claim 12, claim 12 is broader than claim 1. Claim 12 does not recite a specific spike protein fragment nor a specific coronavirus. Claim 12 is not enabled for the same reasons as claim 1, but also because without a more specific spike protein fragment, testing the huge amount of potential fragments of various spike proteins would require undue experimentation. Therefore, claim 12 is rejected.
Regarding claim 13, claim 12 is rejected as described above. Claim 13 provides some guidance on the spike protein fragment, but no target protein is specified nor does this address the issue of the identity of the coronavirus from claim 12. Therefore, claim 13 is rejected.
Regarding claim 14, claim 12 is rejected as described above. The sequences recited by this claim are enabled for the N protein variants from which they are derived, as shown by the data disclosed by the current application. However, as shown above, the sequences of the N proteins of various coronaviruses do not possess a high degree of identity. Determination of the ability of any given spike protein fragment’s ability to bind to the open-ended number of coronaviruses would require undue experimentation due to the number of coronaviruses and the divergent nature of their N protein sequences. Consequently, claim 8 is rejected.
Regarding claim 15, claim 12 is rejected as described above. Claim 15 further specifies various coronavirus variants. However, claim 12 recites an open-ended number of spike protein fragments. Determination of which spike protein fragments bind to the recited coronavirus variants would require undue experimentation. Consequently, claim 15 is rejected.
Regarding claim 16, claim 12 is rejected as described above. The addition of a cell penetrating peptide may certainly improve cellular uptake, but does not further enable N protein binding in and of itself. Therefore, for the reasons listed in claim 12, claim 16 is rejected.
Regarding claim 17, claim 16 is rejected as described above. Claim 17 further defines the cell penetrating peptide of claim 16. This does not further enable N protein binding. Therefore, claim 17 is rejected.
Claim Rejections - 35 USC § 102
In the event the determination o