DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the cited rejections will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
3. Response to Election/Restriction filed on 3/5/2026 is acknowledged.
4. Claim filed on 10/18/2023 is acknowledged.
5. Claims 2, 3, 5-8, 10-21, 24, 25, 28-32, 34, 36, 39, 41-59 and 61-67 have been cancelled.
6. New claims 68-74 have been added.
7. Claims 1, 4, 9, 22, 23, 26, 27, 33, 35, 37, 38, 40, 60 and 68-74 are pending in this application.
8. Claims 38, 40, 60 and 69-74 are withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claim 35 is withdrawn from consideration as being drawn to non-elected species.
9. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are under examination.
Election/Restrictions
10. Applicant’s election without traverse of Group 1 (claims 1, 4, 9, 22, 23, 26, 27, 33, 35, 37 and 68) and election without traverse of a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier being the additional component as species of composition in the reply filed on 3/5/2026 is acknowledged. The requirement is made FINAL in this office action.
Group 1 is drawn to a composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect. A search was conducted on the elected species; and prior art was found. Claim 35 is withdrawn from consideration as being drawn to non-elected species. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are examined on the merits in this office action.
Sequence Non-Compliance
11. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below. All sequences disclosed in the application must comply with the requirements of 37 C.F.R. 1.821-1.825, not only those recited in the claims.
In the instant case, the instant specification discloses the peptide His6 on page 22, line 28 of instant specification. However, this peptide is not disclosed in the filed sequence listing.
All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database.
Claim Interpretations
12. With regards to the recited collagen type VI polypeptides, the instant specification discloses that “A "polypeptide" is used herein in its broadest sense to refer to a compound of two or more subunit amino acids, amino acid analogues, or other peptidomimetics. The term "polypeptide" thus includes short peptide sequences and also longer polypeptides and proteins.”; and “By an amino acid sequence "derived from" collagen type VI and/or the α1, α2 and/or α3 chain of collagen type VI we include amino acid sequences found within the amino acid sequence of a naturally occurring collagen type VI protein and/or the α1, α2 and/or α3 chain of collagen type VI” (see page 8, lines 19-29 of instant specification). Therefore, for the purpose of this examination, the Examiner is interpretating each of the recited collagen type VI polypeptide broadly includes any peptide and/or protein comprising at least 2 contiguous amino acids from collagen type VI or its fragment, variant or derivative thereof or being a fusion protein comprising said amino acid sequence from collagen type VI or its fragment, variant or derivative thereof; and the recited collagen type VI polypeptide can be the naturally occurring collagen type VI protein.
With regards to the term “variant” recited in instant claims, the instant specification discloses that “By "variants" of the polypeptide we include insertions, deletions and substitutions, either conservative or non-conservative.” (see page 20, lines 28-29 of instant specification”. Therefore, in view of the disclosure of instant specification and in the broadest reasonable interpretation, other than the variant recited in instant claim 26, a collagen type VI polypeptide comprising a variant of an amino acid sequence derived from collagen type VI broadly includes any peptide and/or protein that has the recited function and/or property.
With regards to the term “derivative” recited in instant claims, the instant specification fails to define it. Therefore, in the broadest reasonable interpretation, a collagen type VI polypeptide comprising a derivative of an amino acid sequence derived from collagen type VI broadly includes any peptide and/or protein that has the recited function and/or property.
With regards to the limitation recited in instant claim 26, in the instant case, claim 26 further limits the variant of the first and/or second peptide recited in instant claim 1. Since claim 26 depends on claim 1, and includes all the limitations of instant claim 1; claim 26 is interpretating as “A composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect; and wherein the variant of the first and/or second polypeptide has at least 50% identity with the amino acid sequence amino acid sequence of any one of SEQ ID NOs: 1 to 23”.
Such interpretations apply to all the rejections set forth below.
Duplicate Claims Warning
13. Applicant is advised that should claim 33 be found allowable, claim 68 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. 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)).
Objections
14. The specification is objected to for the following minor informality: The specification discloses the peptide His6 on page 22, line 28 of instant specification. However, this peptide is not disclosed in the filed sequence listing; and it is missing the respective sequence identifier.
Applicant is required to amend the specification to comply with 37 CFR 1.821(c) and 1.821(d).
15. The specification is objected to for the following minor informality: The specification recites various hyperlinks on page 7, lines 9 and 12-17; page 58, lines 10 and 11; and page 59, line 5 of instant specification. The embedded hyperlinks and/or other forms of browser-executable code are impermissible and require deletion. It is suggested that Applicant places a URL between these symbols “< >” to inactivate the hyperlinks. Applicant is required to correct these errors.
Please note: The specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
16. Claim 1 is objected to for the following minor informality: Applicant is suggested to amend claim 1 as “A composition comprising: (a) a first polypeptide comprising an amino acid sequence derived from collagen type VI or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, wherein the first polypeptide promotes wound healing; and (b) a second polypeptide comprising an amino acid sequence derived from collagen type VI or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, wherein the second polypeptide exerts antimicrobial effect”.
17. Claim 4 is objected to for the following minor informality: Applicant is suggested to amend claim 4 as “The composition of claim 1, wherein the first and/or second polypeptide: a) binds to membrane of microorganism; and/or b) disrupts membrane of microorganisms; and/or c) enhances epithelia regeneration; and/or d) enhances healing of wound epithelia; and/or e) enhances healing of wound stroma; and/or f) exhibits an antimicrobial effect greater than or equal to that of LL-37; and/or g) is non-toxic to mammalian cells; and/or h) exerts an anti-endotoxic effect; and/or i) comprises an amin acid sequence derived from a von Willebrand Factor type A domain of collagen type VI; and/or j) comprises an amin acid sequence derived from the α1, α2 and/or α3 chain of collagen type VI; and/or k) comprises an amin acid sequence derived from the N2, N3 or C1 domain of the α3 chain of collagen type VI; and/or l) has a net positive charge; and/or m) has at least 30% hydrophobic residues; and/or n) is a recombinant polypeptide; and/or o) kills or attenuates growth of microorganisms; and/or p) promotes wound closure; and/or q) comprises one or more amino acids that are modified by PEGylation, amidation, esterification, acylation, acetylation and/or alkylation”.
18. Claim 9 is objected to for the following minor informality: Applicant is suggested to amend claim 9 as: “The composition of claim 1, wherein the antimicrobial effect is against Gram-positive or Gram-negative bacteria”.
19. Claim 22 is objected to for the following minor informality: Applicant is suggested to amend claim 22 as “The composition of claim 1, wherein the first and/or second polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 23 or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, and wherein the first and/or second polypeptide retains antimicrobial activity of any one of SEQ ID NOs: 1 to 23”.
20. Claim 23 is objected to for the following minor informality: Applicant is suggested to amend claim 23 as: “The composition of claim 1, wherein the first and/or second polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, and wherein the first and/or second polypeptide retains antimicrobial activity of any one of SEQ ID NOs: 1 to 5”.
21. Claim 26 is objected to for the following minor informality: Applicant is suggested to amend claim 26 as “The composition of claim 1, wherein the first and/or second polypeptide comprises the amino acid sequence that is at least 50% identical to the amino acid sequence of any one of SEQ ID NOs: 1 to 23”.
22. Claim 27 is objected to for the following minor informality: Applicant is suggested to amend claim 27 as: “The composition of claim 1, wherein the first and/or second polypeptide: (a) is between 10 and 200 amino acids in length; (b) is at least 20 amino acids in length; and/or (c) are present in the composition at a ratio of at least 0.5:1”.
23. Claims 33 and 68 are objected to for the following minor informality: Applicant is suggested to amend claims 33 and 68 as “The composition of claim 1, wherein: (a) the first polypeptide comprises the amino acid sequence of SEQ ID NO:1 or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, wherein the first polypeptide maintains the wound healing activity of SEQ ID NO: 1; and/or (b) the second polypeptide comprises the amino acid sequence of SEQ ID NO:5 or its fragment, variant or derivative thereof, or being a fusion protein comprising said amino acid sequence, fragment, variant of derivative thereof, wherein the second polypeptide retains the antimicrobial activity of SEQ ID NO: 5”.
24. Claim 37 is objected to for the following minor informality: Applicant is suggested to amend claim 37 as: “The composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable…”.
Rejections
Claim Rejections - 35 U.S.C. § 101
25. 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.
26. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are directed to a composition comprising multiple natural products.
Both polypeptides in the recited composition can be the naturally occurring collagen type VI protein and/or fragments of the naturally occurring collagen type VI protein.
Furthermore, as disclosed in Sambursky et al (US 2016/0279194 A1), histatin 1 (a natural product) or histatin 2 (a natural product) promotes wound healing, for example, page 1, paragraph [0006]. And, both histatin 1 and histatin 2 are either variant or derivative of an amino acid sequence derived from collagen type VI, including being variant or derivative of the amino acid sequence of any one of instant SEQ ID NOs: 1-23.
In addition, as disclosed in Du et al (Front. Cell. Infect. Microbiol., 2017, 7, pages 1-12), histatin 5 (a natural product) has potent bactericidal activity, for example, Title. And histatin 5 is either variant or derivative of an amino acid sequence derived from collagen type VI, including being variant or derivative of the amino acid sequence of any one of instant SEQ ID NOs: 1-23.
In the broadest reasonable interpretation, water is a pharmaceutically acceptable excipient recited in instant claim 37. And as evidenced by the Water document (from http://www.biology-online.org/dictionary/Water, 2014, enclosed pages 1-3), water is a natural product.
The claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed composition in instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 does not recite features or steps demonstrating a marked difference from what exists in nature; and the claimed composition in instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 does not recite meaningful limitations that add something of significance to the judicial exception. Therefore, the claimed composition in instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 is not significantly different than a judicial exception (natural product).
Claim Rejections - 35 U.S.C. § 112 paragraph (b)
27. 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.
28. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 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.
29. Claim 1 recites the limitations “wherein the first polypeptide has the primary activity of being capable of promoting wound healing” and “wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect”. With regards to the term “primary activity”, the instant specification fails to define it. Therefore, it is unclear what is considered as a primary activity for any polypeptide having more than one activities; and what is encompassed within the recited “wherein the first polypeptide has the primary activity of being capable of promoting wound healing” and “wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect”. As an example, the instant specification discloses polypeptide of instant SEQ ID NOs: 1-4 have both antimicrobial activity and wound healing activity. However, the instant specification fails to disclose which of these activities is considered as the primary activity of the polypeptides of instant SEQ ID NOs: 1-4. Taken all these together, the metes and bounds of instant claim 1 is vague and indefinite. Because claims 4, 9, 22, 23, 26, 27, 33, 37 and 68 depends from indefinite claim 1, and they do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
30. Claim 4 is indefinite for the following reasons:
First, claim 4, which depends on claim 1, recites the limitation “the microorganisms”. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not mention any microorganism. It is not clear to what the said phrase is referring.
Second, claim 4 recites the limitation “is capable of exhibiting an antimicrobial effect greater than or equal to that of LL-37”. However, the antimicrobial effect depends on the tested conditions. As an example, Mörgelin et al (WO 2017/125585 A2, filed with IDS) teach depends on the tested condition, the antimicrobial effect of the tested polypeptides varies significantly, for example, Figure 9. Therefore, it is unclear what is encompassed within the recited “is capable of exhibiting an antimicrobial effect greater than or equal to that of LL-37”.
Third, claim 4 recites the limitation “is substantially non-toxic to mammalian cells”. With regards to the term “substantially”, the instant specification fails to define it. Therefore, it is unclear what is considered as being substantially non-toxic to mammalian cells.
Fourth, claim 4 recites the term “preferably”. The term “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention (see MPEP § 2173.05(d)).
Fifth, claim 4 recites various optionally limitations. It is unclear whether such recitations further limit the charge, the microorganism and/or the amino acids that are modified or derivatized or not. In the instant case, it appears such recitations are preferred embodiments.
Taken all these together, the metes and bounds of instant claim 4 is vague and indefinite.
31. Claim 9 recites various parenthetical expressions, for example “(e.g. Streptococcus pyogenes)” and many others. The metes and bounds of claim 9 is rendered vague and indefinite by these parenthetical recitations because it is unclear as to whether these limitations are part of the instantly claimed subject matter. Furthermore, claim 9 recites various optionally limitations. It is unclear whether such recitations further limit the microorganism or not. In the instant case, it appears such recitations are preferred embodiments.
In addition, claim 9 recites the term “e.g.”. The term “e.g.” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention (see MPEP § 2173.05(d)).
Taken all these together, the metes and bounds of instant claim 9 is vague and indefinite.
32. Claim 26 recites the term “for example”. The term “for example” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention (see MPEP § 2173.05(d)).
33. Claim 27 recites the terms “preferably” and “for example”. The terms “preferably” and “for example” render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention (see MPEP § 2173.05(d)).
Furthermore, claim 27 recites the limitations “(b) is part of a longer amino acid sequence, wherein the first and/or second polypeptide is part of an amino acid sequence that is up to 25, 28, 30, 33, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 amino acids in length” and “(c) is part of a longer amino acid sequence, wherein the first and/or second polypeptide is part of an amino acid sequence that is between 20 and 200, 28 and 200, 33 and 200, 28 and 150, 33 and 150, 28 and 100, 33 and 100, 28 and 50, 33 and 50, 28 and 40, 33 and 40, or 28 and 33 amino acids in length”. It is unclear what is encompassed within these recitations. Do these recitations mean the instant claimed polypeptide is a fusion protein, or do these recitations limit the length of instant claimed polypeptide.
In addition, claim 27 recites the limitation “(e) are present in the composition at a ratio of at least 0.5:1…”. It is unclear what the unit of the recited ratio is, such as molar ration, weight ratio and so on.
Taken all these together, the metes and bounds of instant claim 27 is vague and indefinite.
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Written Description
34. 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.
35. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 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 MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP § 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP § 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are drawn to a composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect.
The genus of each of instant claimed polypeptides is extremely broad, including any polypeptide and/or protein that is at least 2 amino acids in length.
The instant specification discloses polypeptides of instant SEQ ID NOs: 1-23 as a polypeptide consisting of an amino acid sequence derived from collagen type VI.
The issue at question is whether a person of ordinary skilled in the art would be able to determine what structural feature/amino acid sequence is required for the instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect or not.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
In the instant case, the instant specification discloses polypeptides of instant SEQ ID NOs: 1-23 as a polypeptide consisting of an amino acid sequence derived from collagen type VI.
The instant specification further discloses polypeptides of instant SEQ ID NOs: 1-5 and 7-23 exert an antimicrobial effect; and the polypeptides of instant SEQ ID NOs: 1-4 promote wound healing. The instant specification also discloses that the polypeptide of instant SEQ ID NO: 6 does not have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect.
Furthermore, a composition comprising the polypeptide of instant SEQ ID NO: 1 and the polypeptide of instant SEQ ID NO: 5 is tested in the working examples in instant specification.
Taken all these together, other than the limited examples, the instant specification fails to describe a general correlation between structure and function for the claimed genus of polypeptide; and a person of ordinary skilled in the art would not be able to determine what structural feature/amino acid sequence is required for the instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure:
As discussed above, in the instant case, based on the disclosure of instant specification, other than the limited examples, a person of ordinary skilled in the art would not be able to determine what structural feature/amino acid sequence is required for the instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect.
With regards to the instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect, Mörgelin et al (WO 2017/125585 A2, filed with IDS) teach polypeptides of SEQ ID NOs: 1-5 (identical to the polypeptides of instant SEQ ID NOs: 1-5) exert an antimicrobial effect and polypeptides of SEQ ID NOs: 1-4 (identical to the polypeptides of instant SEQ ID NOs: 1-4) promote wound healing; while polypeptide of SEQ ID NO: 5 (identical to the polypeptide of instant SEQ ID NO: 5) does not promote wound healing, and polypeptide of SEQ ID NO: 6 (identical to the polypeptide of instant SEQ ID NO: 6) does not have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect, for example, page 39, lines 25-30; and Figures 6-17. However, Mörgelin et al do not describe a general correlation between structure and function for these polypeptides.
Furthermore, it is well known in the peptide/protein art that even single amino acid changes or differences in the amino acid sequence of a protein can have dramatic effects on the protein’s function. As an example of the unpredictable effects of mutations on protein function, Drumm et al (Annu. Rev. Pathol. Mech. Dis., 2012, 7, pages 267-282) teach cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, for example, page 268, Section “CYSTIC FIBROSIS”. Drumm et al further teach several mutations can cause cystic fibrosis, including two mutations G551D and G551S; and clinical consequences are quite different for these two changes, as the G551D variant has virtually no detectable activity, and consequently a classic, severe phenotype is associated; G551S, however, has reduced but clearly detectable function and is associated with a much milder presentation of CF, for example page 269, left column, the last paragraph. Drumm et al also teach that in the most common cystic fibrosis mutation ΔF508 (the absence of amino acid 508 of the normally 1,480-amino acid protein) gives rise to the cystic fibrosis phenotype, for example, page 268, right column, the 2nd paragraph. Thus, even the substitution or deletion of a single amino acid can have dramatic and unpredictable effects on the function of the protein. The unpredictability of the effect of amino acid substitution on the function and/or property of peptide/protein is further confirmed and discussed in Yampolsky et al (Genetics, 2005, 170, pages 1459-1472). Yampolsky et al teach even conservative substitution can significantly affect the function of the protein/peptide, for example, page 1465, Table 3. Although the disclosures of Drumm et al and Yampolsky et al are directed to proteins/peptides other than polypeptide either promoting wound healing and/or exerting an antimicrobial effect, they illustrate the inherent unpredictability with respect to the biological activity of a given protein/peptide after even minor changes to the primary amino acid sequence.
Therefore, based on the state of art, a person of ordinary skilled in the art would not be able to determine what structural feature/amino acid sequence is required for the instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect.
(d) representative number of samples:
In the instant case, the genus of each of instant claimed polypeptides is extremely broad, including any polypeptide and/or protein that is at least 2 amino acids in length.
And, as discussed in (a) and (b) above, the instant specification discloses polypeptides of instant SEQ ID NOs: 1-23 as a polypeptide consisting of an amino acid sequence derived from collagen type VI.
The instant specification further discloses polypeptides of instant SEQ ID NOs: 1-5 and 7-23 exert an antimicrobial effect; and the polypeptides of instant SEQ ID NOs: 1-4 promote wound healing. The instant specification also discloses that the polypeptide of instant SEQ ID NO: 6 does not have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect.
Furthermore, a composition comprising the polypeptide of instant SEQ ID NO: 1 and the polypeptide of instant SEQ ID NO: 5 is tested in the working examples in instant specification.
Considering the broadness of the genus of instant claimed polypeptide, the instant specification fails to provide sufficient examples to describe the entire genus of instant claimed polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect claimed.
Taken all these together, considering the state of the art and the disclosure in instant specification, it is deemed that the instant specification fails to provide adequate written description for the claimed genus of polypeptide to have the functional characteristics of either promoting wound healing and/or exerting an antimicrobial effect; and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 U.S.C. § 102(a)(1)
36. 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.
37. Please note: during the search for the elected species, prior art was found for the non-elected species of composition.
Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sambursky et al (US 2016/0279194 A1), and as evidenced by Du et al (Front. Cell. Infect. Microbiol., 2017, 7, pages 1-12).
The instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are drawn to a composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect.
Sambursky et al teach a pharmaceutical composition comprising the first peptide selected from histatin 1 or histatin 2 and the second peptide being histatin 5, wherein the first peptide promotes wound healing, and wherein the pharmaceutical composition is in the form of eye drops, eye gels, and many others, for example, Abstract; page 1, paragraphs [0006] and [0013]; and claims 1, 2 and 17. And as evidenced by Du et al, histatin 5 exerts an antibacterial effect (see for example, Title). Histatin 1, 2 or 5 in Sambursky et al is a polypeptide comprising either a variant or derivative of an amino acid sequence derived from collagen type VI, including being a variant or derivative of instant SEQ ID NOs: 1-5. Therefore, the pharmaceutical composition in Sambursky et al meets the limitations of instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68.
Since the reference teaches all the limitations of instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68; the reference anticipates instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68.
Claim Rejections - 35 U.S.C. § 103
38. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
39. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
40. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Mörgelin et al (WO 2017/125585 A2, filed with IDS).
The instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are drawn to a composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect.
Mörgelin et al, throughout the patent, teach polypeptides comprising an amino acid sequence derived from collagen type VI that is capable of killing or attenuating the growth of microorganism; a pharmaceutical composition comprising such polypeptide and a pharmaceutically acceptable carrier; and method of using such polypeptide and/or pharmaceutical composition for wound care, including promoting wound closure and/or wound healing, for example, Abstract; page 1, lines 10-15; page 4, lines 36-37; page 5, lines 9-10; and page 18, lines 34-36. It meets the limitation of “a pharmaceutically acceptable carrier” recited in instant claim 37. Mörgelin et al further teach polypeptides of SEQ ID NOs: 1-4 (identical to the polypeptides of instant SEQ ID NOs: 1-4) promote wound healing, for example, page 45, Table3; and Figure 13. It meets the limitations of the first polypeptide recited in instant claims 1, 4, 22, 23, 26, 27, 33 and 68. Mörgelin et al also teach polypeptides of SEQ ID NOs: 1-5 (identical to the polypeptides of instant SEQ ID NOs: 1-5) exert antimicrobial effects, including antibacterial effects; and polypeptide of SEQ ID NO: 5 (identical to the polypeptide of instant SEQ ID NO: 5) is the only one that exerts antimicrobial effects under various test conditions, for example, page 45, Table3; and Figures 6-11 and 14-17. It meets the limitations of the second polypeptide recited in instant claims 1, 4, 9, 22, 23, 26, 27, 33 and 68.
The difference between the reference and instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 is that the reference does not explicilty teach a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier being the additional component as the elected species of composition; and the limitations of instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68.
However, Mörgelin et al teach the pharmaceutical composition may comprise one or more such polypeptides comprising an amino acid sequence derived from collagen type VI, for example one, two, three or four different peptides; and by using a combination of different peptides the antimicrobial effect may be increased, for example, page 20, lines 36-38.
Therefore, in view of the teachings of Mörgelin et al as a whole, it would have been obvious to one of ordinary skilled in the art to develop a pharmaceutical composition comprising: the first polypeptide selected from instant SEQ ID NOs: 1-4, wherein the first polypeptide promotes wound healing; the second polypeptide selected from instant SEQ ID NOs: 1-5, in particular instant SEQ ID NO: 5, wherein the second polypeptide exerts antimicrobial activity, such as antibacterial activity; and a pharmaceutically acceptable carrier; wherein the pharmaceutical composition is for wound care, including promoting wound closure and/or wound healing; including a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier. It reads on a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier being additional component as the elected species of composition.
In view of the teachings of Mörgelin et al as a whole, one of ordinary skilled in the art would have been motivated to develop a pharmaceutical composition comprising: the first polypeptide selected from instant SEQ ID NOs: 1-4, wherein the first polypeptide promotes wound healing; the second polypeptide selected from instant SEQ ID NOs: 1-5, in particular instant SEQ ID NO: 5, wherein the second polypeptide exerts antimicrobial activity, such as antibacterial activity; and a pharmaceutically acceptable carrier; wherein the pharmaceutical composition is for wound care, including promoting wound closure and/or wound healing; including a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier, because Mörgelin et al teach the pharmaceutical composition may comprise one or more such polypeptides comprising an amino acid sequence derived from collagen type VI, for example one, two, three or four different peptides; and by using a combination of different peptides the antimicrobial effect may be increased. Furthermore, the MPEP states “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose...” (see MPEP § 2144.06).
In view of the teachings of Mörgelin et al as a whole, a person of ordinary skilled in the art would have reasonable expectation of success in developing a pharmaceutical composition comprising: the first polypeptide selected from instant SEQ ID NOs: 1-4, wherein the first polypeptide promotes wound healing; the second polypeptide selected from instant SEQ ID NOs: 1-5, in particular instant SEQ ID NO: 5, wherein the second polypeptide exerts antimicrobial activity, such as antibacterial activity; and a pharmaceutically acceptable carrier; wherein the pharmaceutical composition is for wound care, including promoting wound closure and/or wound healing; including a composition with GVR28 (SEQ ID NO: 1) being the first collagen type VI polypeptide, SFV33 (SEQ ID NO: 5) being the second collagen type VI polypeptide and a pharmaceutically acceptable carrier.
Obviousness Double Patenting
41. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
42. Claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9 of US patent 10793618 B2 and in view of Mörgelin et al (WO 2017/125585 A2, filed with IDS).
43. Instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are drawn to a composition comprising:(a) a first collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the first polypeptide has the primary activity of being capable of promoting wound healing; and (b) a second collagen type VI polypeptide comprising or consisting of an amino acid sequence derived from collagen type VI, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the second polypeptide has the primary activity of being capable of exerting an antimicrobial effect.
44. Claims 1-9 of US patent 10793618 B2 are drawn to a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) SEQ ID NO: 1 from the α3 chain of collagen type VI; (b) a fragment of SEQ ID NO: 1, wherein the fragment of SEQ ID NO: 1 comprises at least 20 contiguous amino acids of SEQ ID NO: 1; and (c) a variant of SEQ ID NO: 1, wherein the variant comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 1, wherein the polypeptide is between 20 and 200 amino acids in length, and wherein the polypeptide has antimicrobial activity.
The polypeptide of SEQ ID NO: 1 recited in claims 1-9 of US patent 10793618 B2 is identical to the polypeptide of instant SEQ ID NO: 1.
45. The difference between instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 and claims 1-9 of US patent 10793618 B2 is that claims 1-9 of US patent 10793618 B2 do not teach apply the polypeptide in a composition recited in instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68.
However, in view of the teachings of Mörgelin et al as set forth in Section 40 above, it would have been obvious to one of ordinary skilled in the art to apply the polypeptide recited in claims 1-9 of US patent 10793618 B2 in a composition recited in instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68.
46. For the same and/or similar reasoning/rational as the rejection set forth in Sections 42-45 above, instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-19 of US patent 11136374 B2, claims 1-5 of US patent 11814422 B2, and claims 1-19 of US patent 12134640 B2; and in view of the teachings of Mörgelin et al (WO 2017/125585 A2, filed with IDS) as set forth in Section 40 above.
In the instant case, claims 1-5 of US patent 11814422 B2 are in possession of a pharmaceutical composition comprising the polypeptide of instant SEQ ID NO: 1.
47. For the same and/or similar reasoning/rational as the rejection set forth in Sections 42-45 above, instant claims 1, 4, 9, 22, 23, 26, 27, 33, 37 and 68 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 63-81 of co-pending Application No. 18/899857, and in view of the teachings of Mörgelin et al (WO 2017/125585 A2, filed with IDS) as set forth in Section 40 above.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658