Office Action 4: Non-Final Rejection (2024-06-11)
Rejection types: 102 - Lack of Novelty, 103 - Obviousness, Double Patenting

CLAIMS:
AMENDMENTS TO THE CLAIMS

Please amend claims 16, 18, and 20-24. 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 the 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 (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 of any five amino acids;
(b) a peptide consisting of the amino acid sequence VKFNKPFVFLMIEQNTK (SEQ ID NO: 1);

(dc) a peptide consisting essentially of the amino acid sequence RFNRPFLR (SEQ ID NO: 4);
(ed) a peptide consisting essentially of the amino acid sequence of RRRFNRPFLRRR (SEQ ID NO: 8); and
(fe) a peptide consisting essentially of the amino acid sequence of VKFNKPFVFLMIEQNTK (SEQ ID NO: 1).

17\. (Previously Presented) The composition of claim 16, further comprising at least one second peptide or protein.

18\. (Currently Amended) The composition of claim 17, wherein the at least one second protein or peptide is attached to the peptide of (c)-(fe) as a fusion peptide.

19\. (Previously Presented) The composition of claim 18, 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, wherein the peptide of (c)-(fe) further comprises one or more D-amino acids.

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

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

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

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

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

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

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

28\. (Previously Presented) The composition of claim 16, wherein the composition is formulated for intramuscular, intravenous, intraperitoneal, intravesicular, intraarticular, intralesional, or subcutaneous administration.

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.
Please note that this is a 2nd Non-Final to present new double patenting rejections.
Status of the Claims
In the reply filed 3/1/24, Applicants amended claims 16 and 20-24.
Claims 16-28 are pending and under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/10/24 was considered by the examiner.
Claim Rejections-Withdrawn
The rejection of claims 16-28 under pre-AIA  35 U.S.C. 102(b) as being anticipated by Gelber et al. (WO2011/126882, cited on IDS) is withdrawn due to amendment of claim 16.
Response to Arguments
Applicant’s arguments with respect to the rejection above have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
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 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 16-19, 21-23 and 25 are rejected under pre-AIA  35 U.S.C. 102(b) as being anticipated by Cercek et al. (USPN 5,270,171). This is a NEW rejection necessitated by amendment of claim 16.
Cercek et al. teach cancer recognition factor (SCM factor) peptides (Abstract).
Cercek et al. teach the SCM peptide of X1-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K (claim 27). The peptide of Cercek et al. comprises instantly claimed SEQ ID NO: 1 (claim 16 (e)) (please see bolded amino acids). As indicated above, 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) [PGPUB 0077]. In the instant case, Cercek et al. teach that the SCM peptide decrease production TNF (bottom of col. 10). As evidenced by the instant specification, the instantly claimed peptides reduce inflammation by reducing the activity or expression of TNF-alpha [PGPUB 0105]. Therefore, the peptide of Cercek et al. meets the limitation of “consisting essentially” of SEQ ID NO: 1 because it is less than 37 amino acids and doe not affect the basic function of the peptide.
With respect to claims 17-18, the bolded amino acids of the peptide X1-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K (claim 27), meet the limitation of “one second peptide or protein”.
With respect to claim 19, Cercek et al. also teach SCM peptides can be conjugated to biotin, meeting the limitation of epitope tag (top of col. 34).
With respect to claims 21 and 22, the peptide of Cercek et al. is 29 amino acids, meeting the limitation of 37 and 35 amino acid residues or fewer.
With respect to claim 23, Cercek et al. also teach the peptide fragment of M-X2-P-P-X5-X6-K-F-X9-K-P-F-X13-F-X15-MX17-X18-X19-X20-X21-K, wherein X2, X6, X13, X15 and X17 are independently selected from I, L, and V; X5 and X18 are selected from D and E;  X9, X19 and X20 are selected from Q and N; X21 is selected from S and T. The fragment above meets the limitation of 16(e) and is 22 amino acids in length.
With respect to claim 25, Cercek et al. teach the SCM peptides in combination with a pharmaceutically acceptable carrier (col. 13, 1st para.; col. 41, 3rd para.).
Claim Rejections - 35 USC § 103-NEW
The following is a quotation of pre-AIA  35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA  35 U.S.C. 103(a) 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.
Claims 16-19 and 21-28  are rejected under pre-AIA  35 U.S.C. 103(a) as being unpatentable over Cercek et al. (USPN 5,270,171). This is a NEW rejection necessitated by amendment of claim 16.
The teachings of Cercek et al. are presented above. Cercek et al. does not teach the specific peptides consist of 21 or fewer amino acids or formulated for oral, parenteral, intramuscular…or subcutaneous administration (the limitations of claims 24-28). However, the teachings of Cercek et al. are suggestive of the limitations.
Cercek et al. teach fragments of the SCM peptides (col. 7, 2nd para. and part (4)). Cercek et al. teach fragments of 21 amino acids in length, such as F1 (col. 26). Please note that F1 does not meet the limitation of consists essentially of SEQ ID NO: 1 because there are 2 amino acid substitutions in F1 that are not recited in instantly claimed SEQ ID NO:21. Cercek et al. teach that the fragments are expected to have the same activity (bottom of col. 40).
It would have been obvious to a person or ordinary skill in the art to optimize the SCM peptides of Cercek et al. A person of ordinary skill in the art would look to the teachings of Cercek et al. and have a motivation to create fragments of 22 or 21 amino acids in length because Cercek et al. exemplify fragments of the length and teach they are expected to have the same activity. There is a reasonable expectation of success given that Cercek et al. teach the method of making and isolated fragments of the SCM polypeptides (col. 46).
With respect to claims 26-28, Cercek et al. teach the SCM peptides in water (Example 3, col. 42; Example 5, col. 44). Please note that the limitation “formulated for…” is regarded that intended use of a composition or product will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In Re Hack 114, USPQ 161. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitation. In the instant case, the SCM peptide in water are capable of oral administration, cutaneous and subcutaneous (parenteral).
Claims 16-28  are rejected under pre-AIA  35 U.S.C. 103(a) as being unpatentable over Cercek et al. (USPN 5,270,171) in view of Lifetein.com (https://www.lifetein.com/blog/d-amino-acid-peptides-to-resist-common-proteases/ 3/28/2012). This is a NEW rejection necessitated by amendment of claim 16.
The teachings of Cercek et al. are presented above in detail. The reference does not teach the SCM peptide comprise one or more D-amino acids. However, the teachings of Lifetein cure this deficiency.
Lifetein teaches that design of D-peptides have been applied to increase bioactive peptides resistance to endogenous enzymes, as well as their bioavailability. Lifetein teaches that the significantly improved biostability of D-peptides usually leads to longer in vivo circulation times, making D-peptides more attractive and efficient than their L-peptide counterparts.
It would have been obvious to a person of ordinary skill in the art to include D- amino acids in the SCM peptide of Cercek et al. because Lifetein teaches that peptides that incorporate D-amino acids have improved biostability leading to longer circulating time and are more efficient than their L-peptide counterparts. There is a reasonable expectation of success given that peptide incorporating D-amino acids are routine in the art.
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, 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: 1 , wherein the peptide is 17 amino acids and meets the limitations of claims 16.  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 3/1/24 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.
Double Patenting-NEW
Claims 16-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,951,104.
The USPN claims a composition comprising a peptide, wherein the peptide consists of SEQ ID NO: 1. SEQ ID NO: 1 of the USPN is identical to instantly claimed SEQ ID NO: 1. The USPN also claims a second peptide or protein, wherein the second protein or peptide is an epitope tag or half life extender or both, comprises a carrier, comprises an injectable carrier (claims 1-6). Claim 7 of the USPN is a fusion polypeptide of SEQ ID NO: 1 and an epitope tag or half-life extender (claims 7-9). Therefore, the USPN anticipates the instant claims.
Claims 16-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 8,975,224.
The USPN claims a composition for treating an inflammatory condition, comprising administering an oral formulation comprising a peptide consisting of SEQ ID NO: 1. SEQ ID NO: 1 of the USPN is identical to instantly claimed SEQ ID NO: 1. The USPN also claims a second peptide or protein, wherein the second protein or peptide is an epitope tag or half-life extender or both, wherein one of the amino acids is a D-amino acid (claims 1-8). Therefore, the USPN anticipates the instant claims.
Claims 16-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10-13, 22-23 and 26-27 of copending Application No. 18/148,942.
The copending Application claims a method of reducing inflammation in a subject comprising administering SEQ ID NO:2. SEQ ID NO: 2 of the copending Application is identical to instantly claimed SEQ ID NO: 1. The copending application claims oral, parenteral…and intranasal administration. Therefore, the copending Application anticipates the instant claims.
Claims 16-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of 18/582,061 of copending Application No. 18/148,942.
The copending Application claims a method of treating a disease associated with a cytokine storm, a method of reducing infarct size and a method of treating AMI with SEQ ID NO: 1. SEQ ID NO: 1 of the copending Application is identical to instantly claimed SEQ ID NO: 1. The copending Application claims an oral formulation, comprises an epitope tag or half-life extender, comprises D- amino acids, is less than 32, 22 or 21 amino acids and comprises a carrier (claims 1-16). Therefore, the copending Application anticipates the instant claims.
Conclusion
No claims are allowed.

APPLICANT REBUTTAL: REMARKS/ARGUMENTS
Claims 16-28 were pending when the present Office Action was mailed on June 11, 2024 (hereinafter "Office Action" or "OA").
In this response, claims 16, 18, and 20-24 have been amended to address informalities and to further clarify certain features of these claims. Support for these amendments can be found in the application as originally filed, and in the original listing of the claims. No claims have been added or canceled. The foregoing amendments are made solely to expedite prosecution of this application and without prejudice to pursuing these claims in unamended or other forms in a continuation or other application. Applicant respectfully requests entry of this amendment and upon entry, claims 16-28 will remain pending.
l.    Response to the Section 102 Rejections
The Office Action rejected claims 16-28 under 35 U.S.C. § 102(b) as allegedly being anticipated by U.S. Patent No. 5,270,171 ("Cercek"). OA at 4. The Office Action stated that
Cercek et al. teach the SCM peptide of X1-I-P-P-E-V-K-F-N- K-P-F-V-F-L-M-I-E-Q N-T-K-S-P-L-F-M-G-K (claim 27). The
peptide of Cercek et al. comprises instantly claimed SEQ ID
NO: 1 (claim 16 (e)) (please see bolded amino acids). Id.
Without conceding to the rejection, and solely to advance prosecution, Applicant has amended claim 1 to recite "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 (SEQ ID NO: 2), ...; (b) a peptide consisting essentially of the amino acid sequence RFNRPFLR (SEQ ID NO: 4); and (c) a peptide consisting essentially of the amino acid sequence of RRRFNRPFLRRR (SEQ ID NO: 8)." The SCM peptide from Cercek is not encompassed by amended claim 16. As such, the novelty rejection over
claim 16 is moot. Claims 17-28 depend from and incorporate the features of claim 16. Therefore, Applicant requests withdrawal of the §102 rejections over claims 16-28. II.    Response to the Section 103 Rejections
A.   Cercek
The Office Action rejected claims 16-19 and 21-28 under 35 U.S.C. § 103(a) as allegedly being unpatentable over Cercek. OA at 6. The Office Action stated Cercek et al. does not teach the specific peptides consist of 21 or fewer amino acids or formulated for oral, parenteral, intramuscular...or  subcutaneous  administration  (the limitations of claims 24-28). However, the teachings of Cercek
et al. are suggestive of the limitations. OA at 6.
The Office Action also stated that
With respect to claims 26-28, Cercek et al. teach the SCM peptides in water (Example 3, col. 42; Example 5, col. 44).
Please note that the limitation "formulated for..." is regarded that "intended use" of a composition or product will not further
limit claims drawn to a composition or product. OA at 7.
Even if the Office Action's characterization of Cercek is correct, which Applicant does not concede, Cercek still does not teach or suggest "[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 (SEQ ID NO: 2), ...; (b) a peptide consisting
essentially of the amino acid sequence RFNRPFLR (SEQ ID NO: 4); and (c) a peptide consisting essentially of the amino acid sequence of RRRFNRPFLRRR (SEQ ID NO: 8)," as recited in claim 16. Therefore, claim 16 is not obvious over Cercek. Claims 17-19 and 21-28 depend from and incorporate each and every feature of independent claim 16. Applicant requests withdrawal of the §103 rejection of claims 16-19 and 21-28 over Cercek.
B.   Cercek and Lifetein
The Office Action also rejected claims 16-28 under 35 U.S.C. § 103(a) as allegedly
being unpatentable over Cercek and Lifetein.com (www.lifetein.com/blog/d-amino-acid- peptides-to-resist-common-proteases/) ("Lifetein"). OA at 7.
As noted above, claim 16 is not obvious in view of Cercek at least because Cercek
does not teach or suggest the features of claim 16. The Office Action relies on Lifetein for allegedly "teach[ing] that design of D-peptides have been applied to increase bioactive peptides resistance to endogenous enzymes, as well as their bioavailability." Id.
However, Lifetein fails to cure at least the above noted deficiencies of Cercek to support a prima facie § 103 rejection of independent claim 16. Claims 17-28 ultimately depend from and incorporate each and every feature of claim 16. Accordingly, dependent claims 16-28 are allowable over the combination of Cercek and Lifetein and the §103 rejections
over claims 16-28 should be withdrawn.
III.  Response to the Double-Patenting Rejection
Claims 16-26 were rejected on the ground of nonstatutory obviousness-type
double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,214,562;
claims 1-15 of U.S. Patent No. 10,899,797; claims 1-9 of U.S. Patent No. 9,951,104; and
claims 1-8 of U.S. Patent No. 8,975,224.
Claims 16-28 were provisionally rejected on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over 1,3-4, 6-7, 9-10, 13, and 17-27 of copending Application No. 17/215,738 (U.S. Application Publication No.
2021/0369822); claims 1,8, 10-13, 22-23 and 26-27 of copending Application No.
18/148,942 (U.S. Application Publication No. 2023/04006906); and claims 1-16 of
copending Application No. 18/582,061.
As discussed above, independent claim 16 has been amended. The rejections on
the grounds of nonstatutory double patenting are obviated and therefore traversed. MPEP
§ 804(I)(B)(1).
CONCLUSION

NEXT OFFICE 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
Claims 16-28 are pending.
In the reply filed 9/10/24, Applicants amended claims 16, 18 and 20-24.
The 102(b) and 103 rejection of claims 16-19, 21-23 and 25 over Cercek et al. is withdrawn due to amendment of claim to cancel SEQ ID NO: 1.
The rejection of claims 16-28 on the grounds of nonstatutory double patenting over USPN 10,899,797; 9,951,104; 8,975,224 and Applications 17/215,738 and 18/148,942 is withdrawn due to amendment of claim 16 to cancel SEQ ID NO: 1.
The rejection of claims 16-28 on the grounds of nonstatutory double patenting over USPN 10,214,562 is withdrawn due to filing of a TD.
Claims 16-28 are allowed in the Notice of Allowance herewithin.
Terminal Disclaimer
The terminal disclaimer filed on 12/5/24 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of USPN 10,214,562 has been reviewed and is accepted.  The terminal disclaimer has been recorded.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance: Claims 16-28 are allowed. The closest prior art of Cercek et al. (previously presented). However, Cercek et al. does not teach or suggest the peptides of amended claim 16. Cercek et al. does not teach or suggest SEQ ID NO: 2, 4 or 8. A search of the prior art did not uncover any reference that taught SEQ ID NO: 2, 4 and 8.  Therefore, claims 16-28 are free of the art and are novel.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 18-28 are allowed.

CITED REFERENCE SUMMARIES: Ref US5270171A: Claims:
A substantially purified cancer recognition factor, the factor being a peptide of nine amino acid residues to 35 amino acid residues including a core sequence of nine amino acid residues having an amphipathicity profile substantially equivalent to that of the sequence F-L-M-I-D-O-N-T-K, wherein the sixth amino acid of the core sequence is selected from the group consisting of Q and N, the seventh amino acid of the core sequence is selected from the group consisting of N and Q, and the ninth amino acid of the core sequence is selected from the group consisting of K and R, the factor producing at least a ten percent (10%) decrease in the intracellular fluorescence polarization value of lymphocytes capable of responding in the structuredness of the cytoplasmic matrix (SCM) test as isolated from donors afflicted with cancer.
The cancer recognition factor of claim 1 producing at least a 25 percent decrease in the intracellular fluorescence polarization of SCM-responding lymphocytes from donors afflicted with cancer.
The cancer recognition factor of claim 1 wherein the peptide comprises from 9 to 35 amino acid residues, and wherein the core sequence of 9 amino acid residues is F-X 15 -M-X 17 -X 18 -X 19 -X 20 -X 21 -K, wherein X 15 and X 17 are each independently selected from the group consisting of I, L, and V; X 18 is selected from the group consisting of D and E; X 19 and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T.
The cancer recognition factor of claim 1 wherein the core sequence of 9 amino acid residues is F-L-M-I-D-Q-N-T-K.
The cancer recognition factor of claim 1 wherein the peptide has the sequence F-X -M-X 17 -X 18 - X 19 - X 20 -X 21 -K, wherein X 15 and X 17 are each independently selected from the group consisting of I, L, and V; X 18 is selected from the group consisting of D and E; X 19 and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T.
The cancer recognition factor of claim 5 wherein the peptide has the sequence F-L-M-I-D-Q-N-T-K.
The cancer recognition factor of claim 1 wherein the peptide has the sequence F-X 9 -K-P-F-X 13 -F-X 15 -M-X 17 -X 18 -X 19 -X 20 -X 21 -K, wherein X 13 , X 15 , and X 17 are each independently selected from the group consisting of I, L, and V; X 18 is selected from the group consisting of D and E; X 9 , X 19 , and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T.
The cancer recognition factor of claim 7 wherein the peptide has the sequence F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K.
The cancer recognition factor of claim 1 wherein the peptide has the sequence F-X 9 -K-P-F-X 13 -F-X 15 -M-X 17 -X 18 -X 19 -X 20 -X 21 -K-X 23 -P-X 25 -F-M-G-K, wherein X 13 , X 15 , X 17 , X 23 , and X 25 are each independently selected from the group consisting of I, L and V; X 18 is selected from the group consisting of D and E; X 9 , X 19 , and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T.
The cancer recognition factor of claim 9 wherein the peptide has the sequence F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-V-P-L-F-M-G-K.
The cancer recognition factor of claim 1 wherein the peptide has the sequence M-X 2 -P-P-X 5 -X 6 -K-F-X 9 -K-P-F-X 13 -F-X 15 -M-X 17 -X 18 -X 19 -X 20 -X 21 -K, wherein X 2 , X 6 , X 13 , X 15 , and X 17 are each independently selected from the group consisting of I, L, and V; X 5 and X 18 are each independently selected from the group consisting of D and E; X 9 , X 19 , and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T.
The cancer recognition factor of claim 11 wherein the peptide has the sequence M-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K.
A substantially purified cancer recognition factor useful in the structuredness of the cytoplasmic matrix (SCM) test consisting essentially of a peptide have an amino acid sequence of M-X 2 -P-P-X 5 -X 6 -K-F-X 9 -K-P-F-X 13 -F-X 15 -M-X 17 -X 18 -X 19 -X 20 -X 21 -K-X 23 -P-X 25 -F-M-G-K, wherein X 2 , X 6 , X 13 , X 15 , X 17 , X 23 and X 25 are each independently selected from the group consisting of I, L, and V; X 5 and X 18 are each independently selected from the group consisting of D and E; X 9 , X 19 , and X 20 are each independently selected from the group consisting of Q and N; and X 21 is selected from the group consisting of S and T, the factor producing at least a 10 percent decrease in the intracellular fluorescence polarization value of SCM-responding lymphocytes from donors afflicted with cancer.
A substantially purified cancer recognition factor useful in the structuredness of the cytoplasmic matrix (SCM) test consisting essentially of a peptide of from 29 to 35 amino acid residues including a core sequence at amino acids 14-22 of F-L-M-I-X 18 -Q-N-T-K, wherein X 18 is selected from the group consisting of D and E, the factor producing at least a 10 percent decrease in the intracellular fluorescence polarization value of SCM-responding lymphocytes from donors afflicted with cancer.
The cancer recognition factor of claim 14 wherein the peptide has the sequence X 1 -I-P-P-X 5 -V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-X 23 -P-L-F-M-G-K, wherein X 1 is selected from the group consisting of V, M, and S; X 5 is selected from the group consisting of E and D; and X 23 is selected from the group consisting of T and V.
The cancer recognition factor of claim 15 wherein the factor has the sequence V-I-P-P-E-V=K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-V-P-L-F-M-G-K.
The cancer recognition factor of claim 15 wherein the factor has the sequence M-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-V-P-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the factor has the sequence M-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-P-C-F-M-G-C.
The cancer recognition factor of claim 14 wherein the factor has the sequence X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-C-L-F-M-G-K, wherein X 1 is selected from the group consisting of M and V.
The cancer recognition factor of claim 19 wherein the factor has the sequence M-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-C-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the factor has the sequence X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-R-P-L-F-M-G-K, wherein X 1 is selected from the group consisting of R and S.
The cancer recognition factor of claim 21 wherein the factor has the sequence R-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-R-P-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the factor has the sequence V-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-P-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the factor has the sequence V-I-P-P-E-V-K-F-N-C-P-F-V-F-L-M-I-D-Q-N-T-K-V-P-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the peptide is selected from the group consisting of peptides having amino acid sequences X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-P-C-F-M-G-C and X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-P-C-F-M-G-C-V-V-N-C-T-E, wherein X 1 is selected from the group consisting of R and S.
The cancer recognition factor of claim 25 wherein the peptide has the amino acid sequence R-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-D-Q-N-T-K-C-P-C-F-M-G-C.
The cancer recognition factor of claim 14 wherein the peptide is selected from the group consisting of peptides having amino acid sequences X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K and X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K-V-V-N-P-T-Q, wherein X 1 is selected from the group consisting of V and S.
The cancer recognition factor of claim 27 wherein the peptide has the amino acid sequence V-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K.
The cancer recognition factor of claim 14 wherein the factor has the amino acid sequence X 1 -I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K-V-V-N-P-T-Q, wherein X 1 is selected from the group consisting of S and V.
The cancer recognition factor of claim 29 wherein the peptide has the amino acid sequence S-I-P-P-E-V-K-F-N-K-P-F-V-F-L-M-I-E-Q-N-T-K-S-P-L-F-M-G-K-V-V-N-P-T-Q.
A substantially purified cancer recognition factor active in the structuredness of the cytoplasmic matrix (SCM) test consisting essentially of low molecular weight peptide passing through filters with a nominal 1000-dalton molecular weight cutoff and retained by filters with a nominal 500-dalton molecular weight cutoff, the factor being substantially free of intact Î± 1 -antitrypsin or other molecules larger than about 10,000 daltons, the factor producing at least a 10 percent decrease in the intracellular fluorescence polarization value of SCM-responding lymphocytes from donors afflicted with cancer as measured by the standard SCM test.
The cancer recognition factor of claim 31 producing at least a 25 percent decrease in the intracellular fluorescence polarization value of SCM-responding lymphocytes from donors afflicted with cancer as measured by the standard SCM test.
A method for testing lymphocytes obtained from a mammalian donor for the presence or absence of malignancy in the donor comprising the steps of: (a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 1, and (b) determining the decrease in the structuredness of the cytoplasmic matrix of the lymphocytes resulting from the step of contacting the suspension of the lymphocytes.
(a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 1, and
(b) determining the decrease in the structuredness of the cytoplasmic matrix of the lymphocytes resulting from the step of contacting the suspension of the lymphocytes.
The method of claim 33 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P C , for a second aliquot of the lymphocytes that has not been contacted with the cancer recognition factor; and (c) determining the ratio of P S to P C , whereby a ratio of P S to P C of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
(a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor;
(b) measuring the fluorescence polarization, P C , for a second aliquot of the lymphocytes that has not been contacted with the cancer recognition factor; and
(c) determining the ratio of P S to P C , whereby a ratio of P S to P C of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
The method of claim 33 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P M , for a second aliquot of the lymphocytes that has been contacted with a mitogen selected from the group consisting of phytohaemagglutinin, concanavalin A, and pokeweed mitogen; and (c) determining an SCM response ratio, R SCM , as the ratio of P S to P M , whereby an RR SCM of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
(b) measuring the fluorescence polarization, P M , for a second aliquot of the lymphocytes that has been contacted with a mitogen selected from the group consisting of phytohaemagglutinin, concanavalin A, and pokeweed mitogen; and
(c) determining an SCM response ratio, R SCM , as the ratio of P S to P M , whereby an RR SCM of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
A method for screening a blood sample for the presence of a malignancy in the body of the donor of the blood sample comprising the steps of: (a) separating potentially SCM-responding lymphocytes from the blood sample; (b) contacting the separated lymphocytes with the substantially purified cancer recognition factor of claim 1 to stimulate the lymphocytes; (c) contacting the stimulated lymphocytes with a fluorogenic agent precursor for a sufficient time for the precursor to penetrate the lymphocytes for intracellular enzymatic hydrolysis to a fluorogenic agent, thereby generating stimulated fluorogenic agent-containing lymphocytes; (d) exciting the stimulated fluorogenic agent-containing lymphocytes with polarized light thereby causing the lymphocytes to fluoresce; (e) measuring the vertically polarized and horizontally polarized fluorescence emissions from the fluorescing lymphocytes for determining a polarization value for the fluorescing lymphocytes; and (f) comparing the determined polarization value for the stimulated lymphocytes with a polarization value for a control aliquot of lymphocytes from the same donor which has been subjected to the operation of steps (a), (c), (d), and (e) but not (b), thereby to indicate the presence or absence of cancer in the body of the donor of the lymphocytes.
(a) separating potentially SCM-responding lymphocytes from the blood sample;
(b) contacting the separated lymphocytes with the substantially purified cancer recognition factor of claim 1 to stimulate the lymphocytes;
(c) contacting the stimulated lymphocytes with a fluorogenic agent precursor for a sufficient time for the precursor to penetrate the lymphocytes for intracellular enzymatic hydrolysis to a fluorogenic agent, thereby generating stimulated fluorogenic agent-containing lymphocytes;
(d) exciting the stimulated fluorogenic agent-containing lymphocytes with polarized light thereby causing the lymphocytes to fluoresce;
(e) measuring the vertically polarized and horizontally polarized fluorescence emissions from the fluorescing lymphocytes for determining a polarization value for the fluorescing lymphocytes; and
(f) comparing the determined polarization value for the stimulated lymphocytes with a polarization value for a control aliquot of lymphocytes from the same donor which has been subjected to the operation of steps (a), (c), (d), and (e) but not (b), thereby to indicate the presence or absence of cancer in the body of the donor of the lymphocytes.
The method of claim 36 wherein steps (b) and (c) occur simultaneously.
A method for testing lymphocytes obtained from a mammalian donor for the presence or absence of malignancy in the donor comprising the steps of: (a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 13, and (b) determining the decrease of the cytoplasmic matrix of the lymphocytes resulting from the step of contacting the suspension of the lymphocytes.
(a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 13, and
(b) determining the decrease of the cytoplasmic matrix of the lymphocytes resulting from the step of contacting the suspension of the lymphocytes.
The method of claim 38 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P C , for a second aliquot of the lymphocytes that has not been contacted with the cancer recognition factor; and (c) determining the ratio of P S to P C , whereby a ratio of P S to P C of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
The method of claim 38 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P M , for a second aliquot of the lymphocytes that has been contacted with a mitogen selected from the group consisting of phytohaemagglutinin, concanavalin A, and pokeweed mitogen; and (c) determining an SCM response ratio, R SCM , as the ratio of P S to P M , whereby an RR SCM of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
A method for screening a blood sample for the presence of a malignancy in the body of the donor of the blood sample comprising the steps of: (a) separating potentially SCM-responding lymphocytes from the blood sample; (b) contacting the separated lymphocytes with the substantially purified cancer recognition factor of claim 13 to stimulate the lymphocytes; (c) contacting the stimulated lymphocytes with a fluorogenic agent precursor for a sufficient time for the precursor to penetrate the lymphocytes for intracellular enzymatic hydrolysis to a fluorogenic agent, thereby generating stimulated fluorogenic agent-containing lymphocytes; (d) exciting the stimulated fluorogenic agent-containing lymphocytes with polarized light thereby causing the lymphocytes to fluoresce; (e) measuring the vertically polarized and horizontally polarized fluorescence emissions from the fluorescing lymphocytes for determining a polarization value for the fluorescing lymphocytes; and (f) comparing the determined polarization value for the stimulated lymphocytes with a polarization value for a control aliquot of lymphocytes from the same donor which has been subjected to the operation of steps (a), (c), (d), and (e) but not (b), thereby to indicate the presence or absence of cancer in the body of the donor of the lymphocytes.
(b) contacting the separated lymphocytes with the substantially purified cancer recognition factor of claim 13 to stimulate the lymphocytes;
The method of claim 41 wherein steps (b) and (c) occur simultaneously.
A method for testing lymphocytes obtained from a mammalian donor for the presence or absence of malignancy in the donor comprising the steps of: (a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 14; and (b) determining the decrease in the structuredness of the cytoplasmic matrix of the lymphocytes resulting from the step of contacting the suspension of the lymphocytes.
(a) contacting a suspension of the lymphocytes with the substantially purified cancer recognition factor of claim 14; and
The method of claim 43 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P C , for a second aliquot of the lymphocytes that has not been contacted with the cancer recognition factor; and (c) determining the ratio of P S to P C , whereby a ratio of P S to P C of less than about 0.9 indicates the presence of a malignancy in the body of the donor of the lymphocytes.
The method of claim 43 wherein the step of determining the decrease in the structuredness of the cytoplasmic matrix comprises the steps of: (a) measuring the fluorescence polarization, P S , for a first aliquot of the lymphocytes that has been contacted with the cancer recognition factor; (b) measuring the fluorescence polarization, P M , for a second aliquot of the lymphocytes that has been contacted with a mitogen selected from the group
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