Office Action 2: Final Rejection (2023-04-05)
Rejection types: 102 - Lack of Novelty, 112 - Written Description/Enablement, Double Patenting

CLAIMS:
AMENDMENTS TO THE CLAIMS

Please amend claims 16-7 and 20-28. Following is a complete listing of the claims pending in the application, as amended. This listing of claims will replace, without prejudice, all prior versions and listings of claims in the application:

1.-15. (Cancelled) 214

16\. (Currently Amended) A composition comprising a peptide selected from the group consisting of:
(a) a peptide consisting of the amino acid sequence X1-Z1-F-N-K-P-F-X2-Z2- X3-Z3\[\[-Q\]\] (SEQ ID NO: 2), wherein X1 is V or L;
X2 is V, L or M;
X3 is M, I or V;
Z1 is any amino acid;
Z2 is a sequence of any two amino acids; and
Z3 is a sequence any five amino acid;
(b) a peptide consisting of the amino acid sequence VKFNKPFVFLMIEQNTK (SEQ ID NO: 1);
(c) a peptide consisting essentially of the amino acid sequence X1-Z1-F-N-X2- P-F-X3-Z2-X4-Z3-X5 (SEQ ID NO: 3), wherein X1 is V or L;
X2 is K or R;
X3 is V, L or M;
X4 is M, I or V;
X5 is K or Q; Z1 is any amino acid;
Z2 is a sequence of any two amino acids; and
Z3 is a sequence any five amino acids;
(d) a peptide consisting essentially of the amino acid sequence RFNRPFLR (SEQ ID NO: 4)\[\[.\]\]- (e) a peptide consisting essentially of the amino acid sequence of RRRFNRPFLRRR (SEQ ID NO: 8)\[\[.\]\] (f) a peptide consisting essentially of the amino acid sequence of VKFNKPFVFLMIEQNTK (SEQ ID NO: 1); and
(g) a peptide consisting essentially of the amino acid sequence of FNRPFL (SEQ ID NO: 10).

17\. (Currently Amended) The composition of claim 16, further comprisinges at least one second peptide or protein.

18\. (Previously Presented) The composition of claim 17, wherein the at least one second protein or peptide is attached to the peptide as a fusion peptide.

19\. (Previously Presented) The composition of claim 17, wherein the at least one second peptide or protein is an epitope tag or a half-life extender or both.

20\. (Currently Amended) The composition of claim 16, further comprisinges one or more D-amino acids.

21\. (Currently Amended) The composition of claim 16, wherein the peptide consists of 37 amino acid residues or fewer.

22\. (Currently Amended) The composition of claim 16, wherein the peptide consists of 35 amino acid residues or fewer.

23\. (Currently Amended) The composition of claim 16, wherein the peptide consists of 22 amino acid residues or fewer.

24\. (Currently Amended) The composition of claim 16, wherein the peptide consists of 21 amino acid residues or fewer.

25\. (Currently Amended) The composition of claim 16, further comprising a pharmaceutically acceptable carrier.

26\. (Currently Amended) The composition of claim 16, wherein the composition is formulated for oral administration.

27\. (Currently Amended) The composition of claim 16, wherein the composition is formulated for parenteral, intraperitoneal, rectal, cutaneous, nasal, vaginal, inhalant, or ocular administration.

28\. (Currently Amended) The composition of claim 16, wherein the composition is formulated for intramuscular, intravenous, intraperitoneal, intravesicular, intraarticular, intralesional, or subcutaneous administration.
\-2- -3- -4- 159019720.3

OFFICE ACTION:
DETAILED ACTION
Notice of Pre-AIA  or AIA  Status
The present application is being examined under the pre-AIA  first to invent provisions.
Status of the Claims
In the reply filed 1/12/23, Applicants amended claims 16-17 and 20-28.
Claims 16-28 are pending and under consideration.
Examiner’s comment
The Applicants arguments refer to a Declaration filed under 37 CFR 1.132 by Dr. Gelber disclosing the different characteristics of the claimed peptides. However, no such Declaration was submitted. A Declaration filed under 37 CFR 1.132 was submitted disclosing the inventors are the same for the instant application and WO2011/126882 (addressed in detail after the 102 rejection). However, there was no discussion of the properties of the peptides in the Declaration submitted.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/12/23 was considered by the examiner.
Specification-Withdrawn
The objection to the specification is withdrawn due to correction of the sequence in the claims.
Drawings
The drawings were received on 1/12/23.  These drawings are acceptable.
Claim Rejections - Withdrawn
The rejection of claims 16-17 and 21-28 under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter is withdrawn due to Applicants arguments. In particular, Fig. 3 discloses that the claimed sequences are able to reduce TNF-alpha levels compared to the full length protein.
The rejection of claims 17 and 20-28 under 35 U.S.C. 112(b) for being indefinite because they depend from a cancelled claim (claim 1) is withdrawn due to amendment of the claims.
The rejection of claim 16 under 35 U.S.C. 112(b) as indefinite because the sequence of SEQ ID NO:2 in the specification does not match the sequence of SEQ ID NO:2 in the sequence listing filed 12/16/20 is withdrawn due to amendment of claim 16 to the correct sequence.
The rejection of claim 16 under 35 U.S.C. 112(b)  because part (a) is internally inconsistent is withdrawn due to amendment of claim 16 to cancel the limitation “wherein the peptide is 37 or fewer amino acids”.
The rejection of claims 16-24 under 35 U.S.C. 112(b) because the language of Claim 16 (c-g) is unclear is withdrawn due to Applicants arguments.
Claim Objections-NEW
Claim 16 is objected to because of the following informalities: please insert “of” in between “sequence” and “any five amino acids” in part (a) and (c).   Appropriate correction is required.
Claim Rejections - 35 USC § 112-Maintained
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.
The rejection of claims 18-24 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 is maintained.
Claims 18-24 are indefinite because: the closed language of Claim 16 (a, b) “consisting of” does not allow additional elements to the peptide. Therefore, the peptide cannot be attached to another peptide, comprise D amino acids or comprise additional amino acids because the closed language of claim 16 does not allow additional elements to the peptide (claims 18-24).
Response to Arguments
Applicant's arguments filed 1/12/23 have been fully considered but they are not persuasive. Applicants argue that the composition is open due to “comprising language”. Applicants argue that the federal circuit has held that closed group designated by the consisting of language is the body of the claim does not limit the open ended comprising language in the claim. Applicants argue that the comprising language of claim 16 allows for additional elements to be attached to the closed list of peptides designated by the “consisting of” language.
This argument is not persuasive. The Examiner agrees that the composition is open. For example, the composition can comprise another peptide as in claim 17. However, the specific peptides of part a) and b) cannot be attached or fused to another peptide because the closed language of the peptide (as in claims 18-24).
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 102-Maintained
The following is a quotation of the appropriate paragraphs of pre-AIA  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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
The rejection of claims 16-28 are rejected under pre-AIA  35 U.S.C. 102(b) as being anticipated by Gelber et al. (WO2010/081131) is maintained.
Gelber et al. teach and claim peptide inhibitors containing SEQ ID NO: 6 (FNRPFL). SEQ ID NO: 6 is identical to instantly claimed SEQ ID NO: 10 (claim 1 and p.30, 44).  SEQ ID NO: 6 from Gelber et al. is identical to instant claimed SEQ ID NO: 10 and meets the limitations of Claim 16(g).
With respect to claims 17-19, Gelber claims the peptides are modified peptides, wherein the modified peptides are fusion proteins (claim 4). Gelber et al. teach the peptide inhibitors can be produced as a fusion protein (p. 48). Gelber et al. teach the fusion proteins include the addition of an immunologically active domain, such as an antibody epitope, to facilitate purification of the fusion protein. Other useful fusions include linking of functional domains, such as active sites from enzymes, cellular targeting signals or transmembrane regions (p. 49).
With respect to claim 20, Gelber et al. teach the peptide can be a mimetic of SEQ ID NO: 6 (top of p. 44). Gelber et al. further teach the goal in the design of the mimetic is to reduce the susceptibility of mimetics to cleavage and inactivation of peptidases. Gelber et al. teach the approach is a variety of modified amino acids, such as D-amino acids (top of p. 45).
With respect to claims 21-24, SEQ ID NO: 6 is 6 amino acid residues in length, meeting the limitation of “35 amino acid residues or fewer”, “22 amino acid residues or fewer” and “21 amino acids or fewer”.
With respect to claim 25, Gelber et al. teach the composition with pharmaceutically acceptable carriers (p. 80, last para.).
With respect to claims 26-28, Gelber et al. teach the composition is formulated for oral and intravenous administration (p. 82). Gelber et al. also teach intranasal administration (p. 83).
Response to Arguments
Applicant's arguments filed 1/12/23 have been fully considered but they are not persuasive. Applicants state that a declaration was submitted to disqualify Gerber et al. as prior art. However, the Declaration is insufficient because the 1) the Declaration references the wrong Gerber et al. reference and 2) the Gerber et al. reference presented above is a 102(b) rejection that was published greater than one year before the effective filing date of the instant invention. Therefore, the rejection is maintained.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 1/12/23 is insufficient to overcome the rejection of claims 16-287 based upon Gerber et al. (WO2010/081131) as set forth in the last Office action because the Declaration is not addressing the correct reference. The Declaration states that the inventors are the same for the instant application and WO2011/126882. However, the reference used in the 102(b) rejection above is WO2010/081131 and was published over one year before the effective filing date of the instant application.
Double Patenting-Maintained
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA  as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 16-26 on the grounds of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,214,562 is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other. Claims 1,10-12 and 15-16 of the USPN claims peptides for oral administration (SEQ ID NO: 1 and 2) that are identical to instantly claimed SEQ ID NO: 1 and 3, anticipating the limitations of claims 16 and 21-25. Claims 2-5,13 and 17 of USPN claims an oral formulation comprising at least one second peptide or protein, wherein the at least one second protein or peptide is attached to the peptide as a fusion peptide, wherein the second peptide is an epitope tag or half-life extender, wherein the peptide comprises one or more D-amino acids, anticipating the limitations of instant claims 17-20. The USPN claim 9 claims the composition comprises a pharmaceutically acceptable carrier, meeting the limitation of claim 25.
The rejection of claims 16-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,899,797 is maintained.
Claims 1 and 4-6 of the USPN claims SEQ ID NO: 3 , wherein the peptide is 21 amino acids or few. SEQ ID NO: 3 o the USPN meets the limitations of claims 16 (b-g), 21-24. The USPN also claims the peptide is fused to another peptide or protein, wherein the peptide or protein is an epitope tag, half-life extender or both, wherein the peptide comprises one or more D-amino acids, wherein the composition further comprises a pharmaceutically acceptable carrier (claim 19-12 of USPN), meeting the limitation of instant claims 17-20. The USPN claims composition is administered orally, subcutaneous, intravenous, intramuscular, intraperitoneal, nasally, rectally, intravaginally, parenterally, intracisternally or topically (claims 13-15 of USPN), meeting the limitations of claims 25-28.
The rejection of claims 16-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-7, 9-10, 13 and 17-1 of copending Application No. 17/215,738 is maintained.
The copending Application claims SEQ ID NO: 1,4, 8, wherein the peptide has a size of 35 amino acids of less, meeting the limitations of claims 16 and 21-24 (copending Application claims 1-3, 13,21, ). The copending Application claims the oral or subcutaneous administration (copending claims 6, 17), meeting the limitation of claims 26-28. The copending Application claims a second peptide or protein attached to the peptide to form a fusion protein, wherein the second peptide is an epitope tag or half-life extender or both, wherein the peptide comprises one or more D-amino acids (copending claims 7, 9-10, 18-20), meeting the limitations of claims 17-20).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/12/23 have been fully considered but they are not persuasive. Applicants request the rejections be held in abeyance until one or more claims are found allowable.
The rejections are maintained because there is no indication of allowable subject matter.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL.  Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action.  In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action.  In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.

APPLICANT REBUTTAL: REMARKS
Claims 16-28 were pending when the Office Action was mailed on October 13, 2022. Claims 1-15 were previously cancelled. In this response, claims 16, 17, and 20- 28 have been amended to further clarify certain features of these claims and to expedite prosecution of this application. The foregoing amendments are made without prejudice to pursuing these claims in unamended or other forms in a continuation or other application. No claims have been added or cancelled by this submission. Because no new matter has been introduced by way of amendment, Applicant respectfully requests entry of this amendment. Upon entry, claims 16-28 will remain pending.
Specification
The Office objected to the disclosure because the sequence of SEQ ID NO: 2 in the claims, sequence listing, and specification does not match. More specifically, the Office noted that SEQ ID NO: 2 recited in the claims has a Q at the end, however SEQ ID NO: 2 in the sequence listing and specification (e.g. at [0080]) do not. Applicant has removed the Q at the end of SEQ ID NO: 2 in claim 1. Accordingly, Applicant requests that the Office withdraw the objection to the specification.
Drawings
Figures 5-6 and 8-9 were objected to for allegedly missing labels at the y-axis. Applicant has added y-axis labels for Figures 5-6 and 8-9 as well as Figure 16 in the replacement drawings filed concurrently with this response. Support for these replacement drawings can be found throughout the specification, for example [0048- 0051], [0058], and FIG. 4. No new matter has been added. In view of the foregoing, Applicant respectfully requests entry of replacement drawings for Figures 5-6, 8-9, and 16.
Claim Rejections - 35 USC § 101
The Office rejected claims 16, 17, and 21-28 under 35 U.S.C. § 101. According to the Office, the claims are not directed to patent eligible subject matter. Specifically, the Office alleged that claims 16-17 and 21-28 are not patent eligible because they are directed to a law of nature or natural principle. Office Action at page 3-6. Applicant respectfully disagrees with the Office's rejection and characterization of these claims for at least the reasons discussed below.
In evaluating whether claims are directed to a law of nature or natural principle, the first query is whether the claim is directed to a process, machine, manufacture, or composition of matter. 79 Fed. Reg. 74621, 74622 (December 16, 2014); MPEP §2106.04(C). The Office stated that claims 16, 17, and 21-28 are directed to a statutory patent-eligible subject matter category, namely a composition of matter. Applicant agrees, and as such, the claims comply with at least this requirement of 35 U.S.C. §101.
The second inquiry is whether the claim is directed to a law of nature, a natural phenomenon, or abstract idea. 79 F.R. at 74621. When a claim includes a nature-based product, the Office must determine if the claim meets the "product of nature" exception by comparing the nature-based product in the claim to its naturally occurring counterpart to identify markedly different characteristics based on structure, function, and/or properties.
Id. If markedly different characteristics are shown, then the claim qualifies as eligible subject matter under 35 U.S.C. §101 (i.e. the analysis does not proceed to step 2B). Id.; MPEP §2106.04(C).
For example, in Molecular Pathology v. Myriad Genetics, Inc., the Federal Circuit used the markedly different characteristics analysis (mentioned above) to conclude that the DNA fragment claimed by [party] was not markedly different from the naturally-
occurring BRCA gene because it had the same structure characteristics and the same functional characteristics. Id.; See also 79 F.R. at 74625 (Section II, Example 2).
In contrast to Myriad, the presently claimed peptides are markedly different from the naturally occurring alpha-1 antitrypsin (AAT) protein because both the structural characteristics and the functional characteristics of these peptides and the naturally occurring peptide are different.
Independent claim 16 is directed to:
"[a] composition comprising a peptide selected from the group consisting of: a peptide consisting of the amino acid sequence X1-Z1-F-N-K-P-F-X2-Z2- X3-Z3 (SEQ ID NO: 2) ... a peptide consisting of the amino acid sequence VKFNKPFVFLMIEQNTK (SEQ ID NO: 1) . . . a peptide consisting essentially of the amino acid sequence X1 -Z1 -F-N-X2-P-F-X3-Z2-X4-Z3-X5 (SEQ ID NO: 3) . . . a peptide consisting essentially of the amino acid sequence RFNRPFLR (SEQ ID NO: 4) . . . a peptide consisting essentially of the amino acid sequence of RRRFNRPFLRRR (SEQ ID NO: 8) . . . a peptide consisting essentially of the amino acid sequence of VKFNKPFVFLMIEQNTK (SEQ ID NO: 1); and . . . a peptide consisting essentially of the amino acid sequence of FNRPFL (SEQ ID NO: 10)." The Office alleged that four of these peptides-SEQ ID NOs: 1, 4, 8, and 10-are fragments of the naturally-occurring protein, AAT. Office Action at pages 4-5. Applicant respectfully disagrees. The peptides of claim 16, including SEQ ID NOs: 1, 4, 8, and 10 are patent eligible because, as a whole, each of the peptides are fragments that, by themselves, do not exist in nature. The Office acknowledged the same and that they rather are fragments of a naturally-occurring protein. See Office Action at page 5 ("Even though fragmentation or truncation structurally changes a protein from its natural state. .
."). The Office has not provided any evidence that any of Applicant's presently claimed peptides, and notably those having SEQ ID NOs 1, 4, 8, and 10, are produced in nature or that they are the natural product of enzymatic digestion of alpha-1 antitrypsin.
Therefore, the Office has not shown that the presently claimed peptide fragments are naturally occurring or a product of nature.
Furthermore, the non-naturally occurring peptides recited in claim 16 are patent eligible at least because they have markedly different structural and functional characteristics compared to AAT. For example, the claimed peptides have markedly different molecular weights, three-dimensional structures, and different occupancy of three-dimensional space because the peptide sequences are shorter than AAT: the claimed peptides consist of 6 amino acids (for SEQ ID NO: 10), 17 amino acids (SEQ ID NO: 1), 8 amino acids (SEQ ID NO: 4), and 12 amino acids (SEQ ID NO: 8), while AAT has 418 amino acid residues1 The shorter peptide sequences make them unable to form the same secondary and tertiary protein structures that affect AAT's structure and function.
Throughout the specification, Applicant showed that truncations in AAT change the function of the peptide. For example, FIG. 18 compared percent of diabetes-free mice that are treated with human alpha-1 antitrypsin (hAAT) versus truncations of the protein, including SEQ ID NO: 1, and the results showed that treatments with the fragments of hAAT (i.e. both SP16 and SP34) showed reduced incidence of diabetes compared to the full protein. FIG. 3 also illustrates how the claimed peptides have different abilities of reducing TNF-a. For example, C36 Core Seq, Short (i.e. SEQ ID No. 10) has a greater ability of reducing TNF-a than the full truncated C-terminal peptide, ATT C36. The entire specification recites examples of different functional characteristics of the claimed peptide sequences.
1 The specification discloses the inventors "designed 18 different peptide based on the hAAT sequence (Accession# AAB59371)." See [0288]. Accession# AAB59371 is the identifier given to human alpha 1 antitrypsin (hAAT) protein. It also provides a full-length 418 hAAT amino acid sequence.
Additionally, and not in acquiescence to the position taken by the Office, Applicant submits a declaration under 37 C.F.R. § 1.132 of co-inventor, Dr. Cohava Gelber, that was submitted on November 24, 2017 during the prosecution of U.S. Patent Application No. 14/370,815. The declaration provides evidence of further markedly different characteristics of the claimed compositions comprising certain peptides, and as an example, a peptide consisting of the amino acid sequence of SEQ ID NO: 1 and its naturally-occurring counterpart, AAT, protein. The declaration establishes that the peptide recited in Applicant's claimed compositions, in the least, (i) exhibits markedly greater anti- inflammatory activity and (ii) has a markedly different activity profile, when compared to its naturally occurring AAT counterpart protein.
Dr. Gelber's declaration, at paragraph 10, describes the evaluation of functional characteristics, i.e., inflammatory activity, of the peptide consisting of the amino acid sequence of SEQ ID NO: 1 and its full-length naturally-occurring AAT protein using an NFKB signaling assay. The assay utilized a THP1-XBlueTM-MD2-CD14 cell line, which stably expresses an NFKB-inducible secreted embryonic alkaline phosphatase (EAP) reporter gene. Stimulation of the cell line with lipopolysaccharide (LPS) results in activation of NFKB signaling and expression of the EAP reporter gene. Expression, and level of expression, of the EAP reporter gene provides a read out of inflammatory response, and degree of inflammatory response, in the assay. Thus, if a test molecule inhibits NFKB signaling in response to LPS stimulation, shown by a reduction in EAP gene expression, the test molecule is understood to have anti-inflammatory activity.
At paragraph 12 and the Figure provided in the declaration, Dr. Gelber describes that, in the assay, the as-recited peptide consisting of the amino acid sequence of SEQ ID NO: 1 (also referred to as "SP16" in the declaration) exhibited markedly greater anti- inflammatory activity in the assay than its naturally-occurring counterpart AAT protein. See paragraph 2, which describes that incubating cells with LPS in the presence of 0.1
mg/ml SP16 peptide resulted in a greater than 80% reduction of NFKB signaling, while incubating cells with LPS in the presence of the same, 0.1 mg/ml, dose AAT protein resulted in no reduction of NFKB signaling. Paragraph 12 further describes and the Figure further shows that incubating the cells with LPS in the presence of 0.5 mg/ml AAT, a dose five times greater than that which resulted in greater than 80% reduction of NFKB signaling by SP16 peptide, still yet only resulted in a 40% reduction of NFKB signaling.
At paragraphs 13 and 14 of the declaration, Dr. Gelber describes that the data in the assay also evidences a marked difference in activity profile between the recited peptide consisting of SEQ ID NO: 1 ("SP16") and its naturally-occurring counterpart AAT protein, i.e., that the AAT protein possesses both pro- and anti-inflammatory activities while the SP16 peptide possesses only anti-inflammatory activity. To verify that the AAT protein has pro-inflammatory activity (in addition to the above-described anti- inflammatory activity) and that this pro-inflammatory activity is detectable by the assay, a "C36" peptide was tested in the assay. The C36 peptide is a naturally-occurring 36 amino acid residue AAT peptide fragment known to have pro-inflammatory activity; it also includes the 17 amino acid sequence of SP16. In the assay, the C36 peptide either failed to reduce LPS stimulated NFKB signaling (doses of 0.05 mg/ml or 0.1 mg/ml; no inflammatory activity) or increased LPS-stimulated NFKB signaling (dose 0.5 mg/ml; pro- inflammatory activity). Thus, the C36 peptide fragment exhibited detectable pro- inflammatory activity in the assay, and the AAT protein (whose amino acid sequence includes the C36 peptide's amino acid sequence) also exhibited this pro-inflammatory activity in the assay. Accordingly, and as Dr. Gelber concludes, the presence of both pro- and anti-inflammatory activity in the AAT protein resulted in its markedly diminished ability reduce LPS-stimulated NFKB signaling relative to the, as-recited peptide consisting of the amino acid sequence of SEQ ID NO: 1, i.e., SP16 peptide.
The declaration from Dr. Gelber provides additional evidence that truncations of the AAT C-terminus (for example SEQ ID NO: 1), have different functional properties from the full-length AAT, and as discussed above, the specification provides data that shows that other truncations, such as SEQ ID NOs: 4, 8, and 10 (e.g. FIG. 3) also have different functional properties from the full-length AAT. For at least this reason, the reasoning in Dr. Gelber's declaration applies to SEQ ID NO: 1 as well as SEQ ID NOs: 4, 8, and 10.
As all of the peptides in claim 16: (i) are peptides that are not found in nature; (ii) have markedly different structural characteristics relative to the naturally-occurring AAT protein; (iii) are markedly more potent in reducing inflammation than the AAT protein; and (iv) have markedly different activity profiles relative to the AAT protein, the composition of claim 16 is eligible for patenting. The §101 rejections over claim 16 should be withdrawn. Claims 17 and 21-28 depend from independent claim 16 and incorporate each and every feature of claim 16. Claims 17 and 21-28 are therefore also not naturally occurring. Therefore, the §101 rejections over claims 16, 17, and 21-28 should be withdrawn.
Claim Rejections - 35 USC § 112
The Office rejected claims 16-28 under 35 U.S.C. 112 (pre-AIA), second paragraph, for allegedly being indefinite for failing to particularly point out and distinctly claim the subject matter which the Applicant regards as the invention.
According to the Office, claim 16 is indefinite for reciting "SEQ ID NO: 1 ... wherein the peptide is 37 or fewer amino acids," when SEQ ID NO: 1 is only 17 amino acids long. Office Action at 6 and 7. However, claim 16 does not recite SEQ ID NO: 1 and instead recites SEQ ID NO: 2. Regardless, Applicant has removed "wherein the peptide is 37 or fewer amino acids" from claim 16 solely to expedite prosecution of the instant application.
According to the Office, claim 16 is indefinite because SEQ ID NO: 2 does not match the sequence listed in the specification or the sequence listing. Office Action at 7.
As stated above, Applicant amended claim 16 to remove the Q residue from SEQ ID NO: 2.
The Office alleged that "the closed language of claim 16 'consisting of does not allow addition [sic.] elements to the peptide. Therefore, the peptide cannot be attached to another peptide, comprise D amino acids or comprise additional amino acids because the closed language of claim 16 does not allow additional elements to the peptide." Office Action at 7.
However, claim 16 is directed to a "composition
comprising
a peptide selected from a group consisting of. . .", and the federal circuit has held that closed group designated by the "consisting" language in the body of a claim does not limit the open-ended "comprising" language in the claim. Mannesmann Demag Corp. v. Engineered Metal Products Co., 793 F.2d 1279, 230 USPQ 45 (Fed. Cir. 1986). See also In re Crish, 393 F.3d 1253, 73 USPQ2d 1364 (Fed. Cir. 2004)." Id., 73 USPQ2d at 1365.2 Therefore, the composition can include more than what is listed in the Markush group.
Similar to the court's analysis in Crish, in the present application the "comprising" language of claim 16 allows for additional elements to be attached to the closed list of peptides listed designated by the "consisting of' language. Accordingly, claims 18-24 are not indefinite because they are directed to additional elements of the open-ended composition of claim 16.
2 MPEP §2111.03; Crish at 73 (The court affirmed the Board's interpretation that the transition phrase "consists" did not limit the claims to only the recited numbered nucleotide sequences of SEQ ID NO:1 and that "the transition language 'comprising' allowed the claims to cover the entire involucrin gene plus other portions of the plasmid, as long as the gene contained the specific portions of SEQ ID NO:1 recited by the claim[s]." 73 USPQ2d at 1366.).
For at least these reasons, independent claim 16 is not indefinite, and the §112 rejection over this claim should be withdrawn. Applicant has amended claims 17 and 20- 18 to be dependent from claim 16, and claims 18 and 19 ultimately depend from claim 16. Claims 17-28 incorporate all of the features of claim 17, therefore they are also not indefinite. Therefore, the §112 rejections over claims 16-28 should be withdrawn.
Claim Rejections - 35 USC § 102
The Office rejected claims 16-28 under pre-AIA 35 U.S.C. § 102(b) as being anticipated by Gelber et al. (WO 2010/081131). Applicant respectfully traverses the rejection.
Applicant submits herewith the declaration of co-inventors Soren Mogelsvang and Cohava Gelber dated July 28, 2020 under 37 C.F.R. §1.132 pursuant to pre-AIA rules. This declaration was submitted during the prosecution of U.S. Patent Application No. 16/286,298, which is a parent application of the present application. Without acquiescing to the Office's rationale, Gelber is therefore disqualified as relevant prior art against the pending claims in view of the foregoing declaration. Therefore, Applicant respectfully requests withdrawal of the § 102 rejection of claims 16-28.
Double Patenting
The Office rejected claims 16-26 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,214,562.
The Office rejected claims 16-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No.10,899,797.
The Office provisionally rejected claims 16-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-7, 9-10, 13 and 17-1 of copending Application No. 17/215,738.
Applicant respectfully requests that the Office hold the foregoing double-patenting rejections in abeyance until one or more claims of the instant application are otherwise found allowable.
CONCLUSION

NEXT OFFICE ACTION: DETAILED ACTION
Notice of Pre-AIA  or AIA  Status
The present application is being examined under the pre-AIA  first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection.  Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.  Applicant's submission of RCE on 7/28/23 and the amendment of claims has been entered.
Status of the Claims
In the reply filed 7/28/23, Applicants amended claims 16 and 18-24.
Claims 16-28 are pending and under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/28/23 was considered by the examiner.
Claim Rejections-Withdrawn
The rejection of claims 18-24 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 is withdrawn due to amendment of the claims.
The rejection of claims 16-28 are rejected under pre-AIA  35 U.S.C. 102(b) as being anticipated by Gelber et al. (WO2010/081131) is withdrawn due to amendment of the claims.
Specification
The title of the invention is not descriptive.  A new title is required that is clearly indicative of the invention to which the claims are directed.
Claim interpretation
The limitation “consisting essentially of” is defined in the specification to only include additional amino acids that do not materially affect the claimed inventions basic and novel characteristics, namely the anti-inflammatory capacity. The definition specifically excludes peptides that have a sequence of a complete serpin protein and excludes peptide sequences that are equal to or longer than 37 amino acids of any naturally occurring serpin protein [PGPUB 0077]. Therefore, the peptides “consisting essentially of” can be embedded in a sequence (must be less than 37 amino acids) as long as the added amino acids do not affect the basic function of the peptide (anti-inflammatory capacity).
Claim Objections-Withdrawn
The objection to claim 16 is withdrawn due to amendment of the claims.
Claim Rejections - 35 USC § 102-NEW
The following is a quotation of the appropriate paragraphs of pre-AIA  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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 16-28 are rejected under pre-AIA  35 U.S.C. 102(b) as being anticipated by Gelber et al. (WO2011/126882, cited on IDS). This is a NEW rejection necessitated by amendment of the claims.
Gelber et al. teach anti-inflammatory D3 peptides, fragment, analogs and derivatives thereof (Abstract). Gelber et al. teach D3 fragments comprising SEQ ID NO: 74, VWFNRPFLIAVSHTHGQTIL [PGPUB0087]. SEQ ID NO: 74 is 20 amino acids in length and meets the limitations of instantly claimed 16(c), wherein X1 is V, Z is W, X2 is R, X3 is L, Z2 is IA, X4 is V, Z3 is SHTHG and X5 is Q. Please note that SEQ ID Nos: 41 and 68-73 also meet the limitations of claim 16 (c).  Gelber et al. teach the D3 peptides for treatment of diseases where inflammation plays a role [0006, 00202].
With respect to claims 17-19, Gelber et al. teach modification of the peptide, such as fusion to serum protein, e.g. serum albumin that can increase the half-life of the D3 peptides [00186].
With respect to claim 20, Gelber et al. teach the peptides comprise at least one or more D-amino acids [00127].
With respect to claims 21-24, SEQ ID NO: 74 of Gelber et al. is 20 amino acids in length.
With respect to claim 25, Gelber et al. teach the peptides formulated with a pharmaceutically acceptable carrier [00164].
With respect to claims 26-28, Gelber et al. teach oral administration and parental (subcutanous, intramuscular, intravenous) [00370].
Double Patenting-Maintained
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA  as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 16-26 on the grounds of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,214,562 is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other. Claims 1,10-12 and 15-16 of the USPN claims peptides for oral administration (SEQ ID NO: 1 and 2) that are identical to instantly claimed SEQ ID NO: 1 and 3, anticipating the limitations of claims 16 and 21-25. Claims 2-5,13 and 17 of USPN claims an oral formulation comprising at least one second peptide or protein, wherein the at least one second protein or peptide is attached to the peptide as a fusion peptide, wherein the second peptide is an epitope tag or half-life extender, wherein the peptide comprises one or more D-amino acids, anticipating the limitations of instant claims 17-20. The USPN claim 9 claims the composition comprises a pharmaceutically acceptable carrier, meeting the limitation of claim 25.
The rejection of claims 16-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,899,797 is maintained.
Claims 1 and 4-6 of the USPN claims SEQ ID NO: 3 , wherein the peptide is 21 amino acids or few. SEQ ID NO: 3 o the USPN meets the limitations of claims 16 (b-f), 21-24. The USPN also claims the peptide is fused to another peptide or protein, wherein the peptide or protein is an epitope tag, half-life extender or both, wherein the peptide comprises one or more D-amino acids, wherein the composition further comprises a pharmaceutically acceptable carrier (claim 19-12 of USPN), meeting the limitation of instant claims 17-20. The USPN claims composition is administered orally, subcutaneous, intravenous, intramuscular, intraperitoneal, nasally, rectally, intravaginally, parenterally, intracisternally or topically (claims 13-15 of USPN), meeting the limitations of claims 25-28.
The rejection of claims 16-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-7, 9-10, 13 and 17-27 of copending Application No. 17/215,738 is maintained.
The copending Application claims SEQ ID NO: 1,4, 8, wherein the peptide has a size of 35 amino acids of less, meeting the limitations of claims 16 and 21-24 (copending Application claims 1-3, 13,21). The copending Application claims the oral or subcutaneous administration (copending claims 6, 17), meeting the limitation of claims 26-28. The copending Application claims a second peptide or protein attached to the peptide to form a fusion protein, wherein the second peptide is an epitope tag or half-life extender or both, wherein the peptide comprises one or more D-amino acids (copending claims 7, 9-10, 18-20), meeting the limitations of claims 17-20).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 7/28/23  have been fully considered but they are not persuasive. Applicants argue that the amendment of claim 16 obviated the rejection.
This argument is not persuasive for the reasons presented above. The ODP rejections are maintained.
Conclusion
No claims are allowed.

CITED REFERENCE SUMMARIES: Ref WO2011126882: Claims:
1. A peptide selected from the group consisting of SEQ ID NOs: 2-98 and peptides set forth in Table 7, and derivatives and conservative amino acid substitution variants thereof.
2. The peptide of claim 1 , wherein the peptide is selected from the group consisting of SEQ ID NO.
6, 11, and 16, and derivatives and conservative substitution variants thereof.
3. The peptide of claim 1, wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NO. 29, 30, 31, 32, 33, 34, and 35 and derivatives and conservative amino acid substitution variants thereof.
4. An isolated peptide selected from the group consisting of SEQ ID NOs: 106-110, an analog, a derivative, a chemical derivative, and a salt thereof, wherein
X!X2X3 is any permutation of amino acids RPP;
X4X5X6X7X8X9X10Xn is any permutation of amino acids MIVWFNRP; χι2χΐ3χΐ4χΐ5χΐ6χΐ7 ^ any permutation of amino acids PLIAVS;
χι8χΐ9χ2οχ2ΐχ22 ig any permutation of amino acids HTHGQ; and
χ23χ24χ25χ26 ^ any permutation of amino adds KVIN,
with the proviso that SEQ ID NOs: 106-110 are not SEQ ID 1.
5. The isolated peptide of claim 1, wherein the peptide is selected from the group consisting of SEQ ID NOs: 106 and 110, an analog, a derivative, a chemical derivative, and a salt thereof.
6. The peptide of claim 1, wherein the peptide is selected from the group consisting of SEQ ID NOs:
111 and 115, an analog, a derivative, a chemical derivative, and a salt thereof.
7. An isolated peptide selected from the group consisting of SEQ ID NO. 117, an analog, a
derivative, a chemical derivative, and a salt thereof, wherein
χ27χ28χ29χ3οχ3ΐ ig any permutation of amino adds SGRPP; and
χ32χ33χ34χ35χ36χ37χ38χ39χ40χ41χ42χ43χ44χ45χ46 ί8 &ny permutadon Qf aminQ ^
QTILFMAKVINPVGA,
with the proviso that SEQ ID NO. 117 is not SEQ ID 1.
8. The peptide of claim 4, wherein the peptide is SEQ ID NO. 118, an analog, a derivative, a
chemical derivative, or a salt thereof.
9. An isolated peptide selected from the group consisting of SEQ ID NOs: 119-123, an analog, a derivative, a chemical derivative, and a salt thereof, wherein
Y1 is M, Nleu or R;
Y2 is W, T, N or H;
Y3 is I or T; and
Y4 is M, Nleu or Thr,
with the proviso that SEQ ID NOs: 119-123 are not SEQ ID 1.
10. The peptide of claim 6, wherein the peptide is is selected from the group consisting of SEQ ID NOs: 120-123, an analog, a derivative, a chemical derivative, and a salt thereof.
11. The peptide of claim 6, wherein the peptide is selected from the group consisting of SEQ ID NOs:
124-131, an analog, a derivative, a chemical derivative, and a salt thereof.
12. The peptide of claim 6, wherein the peptide is SEQ ID NO. 127, an analog, a derivative, a
chemical derivative, and a salt thereof.
13. The peptide of any of the preceding claims, wherein the peptide comprises at least one D-amino acid.
14. The peptide of any of the preceding claims, wherein the peptide comprises at least one beta-amino acid.
15. The peptide of any of the preceding claims, wherein the peptide comprises at least one peptide bond replacement.
16. The peptide of any of the preceding claims, wherein the peptide comprises at least one peptide bond replacement selected from the group consisting of urea, thiourea, carbamate, sulfonyl urea, trifluoroethylamine, ortho-(aminoalkyl)-phenylacetic acid, para-(aminoalkyl)-phenylacetic acid, meta-(aminoalkyl)-phenylacetic acid, thioamide, tetrazole, boronic ester, olefinic group, and derivatives thereof.
17. The peptide of any of the preceding claims, wherein the peptide comprises at least one amino aid selected from the group consisting of homocysteine, phosphoserine, phosphothreonine, phosphotyrosine, hydroxyproline, gamma-carboxyglutamate; hippuric acid, octahydroindole-2- carboxylic acid, statine, l,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid, penicillamine (3- mercapto-D-valine), ornithine, citruline, alpha-methyl-alanine, para-benzoylphenylalanine, para- amino phenylalanine, p-fluorophenylalanine, phenylglycine, propargylglycine, sarcosine, and tert- butylglycine), diaminobutyric acid, 7-hydroxy-tetrahydroisoquinoline carboxylic acid, naphthylalanine, biphenylalanine, cyclohexylalanine, amino-isobutyric acid, norvaline, norleucine, tert-leucine, tetrahydroisoquinoline carboxylic acid, pipecolic acid, phenylglycine,
homophenylalanine, cyclohexylglycine, dehydroleucine, 2,2-diethylglycine, 1-amino-l-  cyclopentanecarboxylic acid, 1-amino-l-cyclohexanecarboxylic acid, amino-benzoic acid, amino- naphthoic acid, gamma-aminobutyric acid, difluorophenylalanine, nipecotic acid, alpha-amino butyric acid, thienyl-alanine, t-butylglycine, and derivatives thereof.
18. The peptide of any of the preceding claims, wherein the peptide inhibits at least one kinase.
19. The peptide of any of the preceding claims, wherein the peptide inhibits at least one kinase
selected from the group consisting of MAPK9 (JNK2), NEK9, MST4, CHEKl (CHKl), SPHKl, SPHK2, MAPK14 (p38 alpha), MAP4K2 (GCK), SGK (SGK1), RPS6KA1 (RSK1), MAPK10 (JNK3), RPS6KA3 (RSK2), RPSKB 1 (p70S6K), BRAF, PRKD2 (PKD2), MAP3K9 (MLK1), MAP3K8 (COT), PRKX, and any combinations thereof.
20. The peptide of any of the preceding claims, wherein the peptide inhibits the production of at least one pro-inflammatory cytokine in a cell.
21. The peptide of any of the preceding claims, wherein the peptide comprises at least one ligand.
22. The peptide of any of the preceding claims, wherein the peptide is PEGylated.
23. The peptide of any of the preceding claims, wherein the peptide is glycosylated.
24. The peptide of any of the preceding claims, wherein the peptide is a fusion protein.
25. A composition consisting essentially of one or more peptide of any of the preceding claims as an active ingredient.
26. A pharmaceutical composition or medicament comprising the composition of claim 25, and a pharmaceutically acceptable carrier.
27. The pharmaceutical composition or medicament of claim 26, further comprising a second
pharmaceutically active agent.
28. Use of a composition of claim 25 for preventing, treating and/or ameliorating immune related and/or inflammatory disease.
29. Use of pharmaceutical composition or medicament of claim 26 or 27 for preventing, treating and/or ameliorate immune related and/or inflammatory diseases.
30. The use of claims 28 or 29, wherein the immune related and/or inflammatory disease is selected from the group consisting of diabetes, pre -diabetic condition, rheumatoid arthritis, chronic obstructive pulmonary disease, and atherosclerosis.
A method of preventing, treating and/or ameliorating an immune related and/or an inflammatory disease in a subject comprising administering to the subject a pharmaceutical composition or medicament of claim 26 or 27.
32. The method of claim 31 , wherein the immune related and/or inflammatory disease is selected from the group consisting of diabetes, pre-diabetic condition, rheumatoid arthritis, chronic obstructive pulmonary disease and atherosclerosis.
33. A method of treating diabetes or pre-diabetic condition in a subject comprising administering to the subject a pharmaceutical composition of claim 26 or 27.
34. A method for treating and/or preventing or inhibiting or slowing the development of rheumatoid arthritis in a subject affected with arthritis, the method comprising: administering to the subject a pharmaceutical composition of claim 26 or 27.
35. The method of claim 34, wherein the subject has not been diagnosed with diabetes.
36. A method for treating and/or preventing or inhibiting or slowing the development of rheumatoid arthritis in a subject that has previously been diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is not being treated with a pharmaceutical composition of claim 26 or 27, and
(b) administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27 to the subject.
37. A method for treating and/or preventing or inhibiting or slowing the development of rheumatoid arthritis in a subject that has been previously diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is being treated with a pharmaceutical composition of claim 26 or 27, and
(b) adjusting the therapeutic regime of the subject such that at least one symptom of rheumatoid arthritis is reduced.
38. The method of claim 37, wherein adjusting the therapeutic regime comprises at least one of:
(a) modulating the dose of the pharmaceutical composition of claim 26 or 27,
(b) modulating the frequency of administration of the pharmaceutical composition of claim 26 or 27, or  (c) altering the site or mode of administration.
39. The method of any of claims 34-38, further comprising a step of diagnosing rheumatoid arthritis in the subject prior to administering the pharmaceutical composition of claim 26 or 27.
40. The method of any of claims 34-39, wherein the subject is diagnosed with rheumatoid arthritis by having increased levels of at least one rheumatoid arthritis marker compared to the level of that marker in a subject not diagnosed with rheumatoid arthritis.
41. The method of claim 40, wherein the rheumatoid arthritis marker is selected from the group consisting of rheumatoid factor, IL6, IL-8 or IL-17.
42. A method for treating an inflammatory disease in a subject, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27.
43. The method of claim 42, wherein the subject does not have or has not been diagnosed with
diabetes.
44. A method for treating an inflammatory disease in a subject that has previously been diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is not being treated with a pharmaceutical composition of claim 26 or 27, and
(b) administering to the subject a therapeutically effective amount of pharmaceutical composition of claim 26 or 27.
45. A method for treating an inflammatory disease in a subject that has been previously diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is being treated with a therapeutic regime comprising a pharmaceutical composition of claim 26 or 27, and
(b) adjusting the therapeutic regime of the subject such that at least one symptom of the inflammatory disease is reduced.
46. The method of claim 45, wherein adjusting the therapeutic regime comprises at least one of:
(a) modulating the dose of the pharmaceutical composition of claim 26 or 27,
(b) modulating the frequency of administration of the pharmaceutical composition of claim 26 or 27, or
(c) altering the site or mode of administration.
47. The method of any of claims 42-46, further comprising a step of diagnosing a subject with an inflammatory disease prior to administering the pharmaceutical composition of claim 26 or 27.
48. The method of any of claims 42-47, wherein the subject is diagnosed with an inflammatory
disease by having increased levels of at least one inflammatory disease marker compared to the level of that marker in a subject not having the inflammatory disease.
49. The method of claim 48, wherein the inflammatory disease marker is IL6, IL-8, or IL-17.
50. A method for preventing, inhibiting, slowing down the progression of COPD and/or treating COPD or a related disorder in a subject affected with COPD or a related disorder comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27.
51. The method of claim 50, wherein the subject does not have diabetes.
52. A method for treating and/or preventing, inhibiting or slowing down the progression of COPD or a related disorder in a subject that has previously been diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is not being treated with a pharmaceutical composition of claim 26 or 27, and
(b) administering a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27 to the subject.
53. A method for treating and/or preventing, inhibiting or slowing down the progression of COPD or a related disorder in a subject that has been previously diagnosed as having diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is being treated with a therapeutic regime comprising a pharmaceutical composition of claim 26 or 27, and
(b) adjusting the therapeutic regime of the subject such that at least one symptom of COPD or a related disorder is reduced.
54. The method of claim 54, wherein adjusting the therapeutic regime comprises at least one of:
(a) modulating the dose of the pharmaceutical composition of claim 26 or 27,
(b) modulating the frequency of administration of the pharmaceutical composition of claim 26 or 27, or
(c) altering the site or mode of administration.
55. The method of any of claims 50-54, further comprising a step of diagnosing a subject with COPD or a related disorder prior to administering the pharmaceutical composition of claim 26 or 27.
56. The method of any of claims 50-55, wherein the subject is diagnosed with COPD or a related disorder by having increased levels of at least one COPD marker compared to the level of that marker in a subject not having COPD or a related disorder.
57. The method of claim 56, wherein the COPD marker is IL6, IL-8, or IL-17.
58. The method of any of claims 50-57, wherein the subject is diagnosed with COPD or a related disorder by assessing lung function in the subject.
59. The method of any of claims 50-58, wherein the pharmaceutical composition of claim 26 or 27 is administered using an inhaler.
60. A method for treating and/or preventing atherosclerosis in a subject, the method comprising: administering to a subject a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27.
61. The method of claim 60, wherein the subject does not have or has not been diagnosed as having diabetes.
62. A method for treating and/or preventing atherosclerosis in a subject that has previously been diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is not being treated with a pharmaceutical composition of claim 26 or 27, and
(b) administering a therapeutically effective amount of a pharmaceutical composition of claim 26 or 27 to the subject.
63. A method for treating and/or preventing atherosclerosis in a subject that has been previously diagnosed with diabetes, the method comprising:
(a) selecting a subject that has been previously diagnosed with diabetes and that is being treated with a therapeutic regime comprising a pharmaceutical composition of claim 26 or 27, and
(b) adjusting the therapeutic regime of the subject such that at least one symptom of
atherosclerosis is reduced.
64. The method of claim 63, wherein adjusting the therapeutic regime comprises at least one of:
(a) modulating the dose of the pharmaceutical composition of claim 26 or 27,
(b) modulating the frequency of administration of the pharmaceutical composition of claim 26 or 27, or
(c) altering the site or mode of administration.
65. The method of any of claims 60-64, further comprising a step of diagnosing a subject as having atherosclerosis prior to administering the pharmaceutical composition of claim 26 or 27.
66. The method of any of claims 60-65, wherein the subject is diagnosed as having atherosclerosis by having increased levels of at least one atherosclerotic marker compared to the level of that marker in a subject not having atherosclerosis.
67. The method of claim 66, wherein the marker is atherosclerotic marker is C-reactive protein, fibrinogen, homocysteine, Lpl, IL6, IL-8 or IL-17.
68. The method of any of claims 34-67, wherein the pharmaceutical composition of claim 26 or 27 thereof is administered topically, systemically, by sustained release, or by local injection.
69. The method of any of claims 34-68, wherein the subject is a mammal.
70. The method of any of claims 34-69, wherein the mammal is a human.
71. The method of any of claims 34-70, wherein the mammal is a non-human mammal.
72. The pharmaceutical composition of claim 26 or 27 for use in the treatment and/or prevention of rheumatoid arthritis in a subject.
73. The use according to claim 72, wherein the subject has not been diagnosed with diabetes.
74. The use of any of claims 72-73, further comprising a step of diagnosing a subject as having
rheumatoid arthritis prior to administering the pharmaceutical composition of claim 26 or 27 thereof.
75. The use of any of claims 72-74, wherein the subject is diagnosed with rheumatoid arthritis by having increased levels of at least one rheumatoid arthritis marker compared to the level of that marker in a subject not having rheumatoid arthritis.
76. The use of claim 75, wherein the rheumatoid arthritis marker is rheumatoid factor, IL6, IL-8 or IL-17.
77. The pharmaceutical composition of claim 26 or 27 for use in the treatment of an inflammatory disease in a subject.
78. The use according to claim 77, wherein the subject does not have or has not been diagnosed with diabetes.
79. The use of any of the claims 77-78, further comprising a step of diagnosing a subject as having an inflammatory disease prior to administering the pharmaceutical composition of claim 26 or 27.
80. The use of claims 77-79, wherein the subject is diagnosed as having an inflammatory disease by having increased levels of at least one inflammatory disease marker compared to the level of that marker in a subject not having the inflammatory disease.
81. The use of claim 80, wherein the inflammatory disease marker is IL6, IL-8 or IL-17.
82. The pharmaceutical composition of claim 26 or 27 for use in the treatment of COPD or a related disorder in a subject that has not been diagnosed with diabetes.
83. The use of claim 82, further comprising a step of diagnosing a subject as having COPD or a
related disorder prior to administering the D3 peptide, analog or a fragment thereof.
84. The use of any of claims 82-83, wherein the subject is diagnosed as having COPD or a related disorder by having increased levels of at least one marker compared to the level of that marker in a subject not having COPD or a related disorder.
85. The use of claim 84, wherein the COPD marker is IL6, IL-8 or IL-17.
86. The use of any of claims 82-85, wherein the subject is diagnosed as having COPD or a related disorder by assessing lung function in the subject.
87. The pharmaceutical composition of claim 26 or 27 for use in the treatment of atherosclerosis in a subject that has not been diagnosed with diabetes.
88. The use of claim 87, further comprising a step of diagnosing a subject as having atherosclerosis prior to administering the D3 peptide or a fragment thereof.
89. The use of any of claims 87-88, wherein the subject is diagnosed as having atherosclerosis by having increased levels of at least one atherosclerotic marker compared to the level of that marker in a subject not having atherosclerosis.
90. The use of claim 89, wherein the marker is C-reactive protein, fibrinogen, homocysteine, Lpl, IL6, IL-8 or IL-17.
91. The use of any of claims 56-82, wherein the D3 peptide, analog or fragment thereof is administered topically, systemically, by sustained release, or by local injection.
92. The use of any of claims 72-91, wherein the subject is a mammal.
93. The use of claim 92, wherein the mammal is a human.
94. The use of claim 92, wherein the mammal is a non-human mammal.
95. A method for promoting islet cell differentiation from a progenitor cell, the method comprising: contacting the progenitor cell with an effective amount of th
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