Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Status
Claims 14, 16, 19-21, 24, 31-34 and 42-51 are pending. Claims 42-51 have been added. Claim 14 has been amended. Claims 14, 16 and 42-46 are being examined in this application. In the response to the restriction requirement, Applicants elected Group I, mitomycin and SEQ ID NO: 1. Claims 19-21, 24, 31-38, 40-41 and 47-51 are withdrawn as being drawn to a nonelected species/invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
This rejection is maintained.
Claims 14, 16 and 44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a pharmaceutical composition comprising a first chemotherapeutic agent, a second chemotherapeutic agent, and a pharmaceutically acceptable carrier, excipient and/or adjuvant, wherein the first chemotherapeutic agent is mitomycin, and wherein the second chemotherapeutic agent comprises a biologically active complex having anti-tumour activity, wherein the biologically active complex consists of: a peptide comprising an N-terminal alpha helical domain derived from alpha-lactalbumin, wherein the peptide comprises or consists of SEQ ID NO: 1, or a variant comprising an amino acid sequence with at least 94% sequence identity to SEQ ID NO: 1, wherein the variant comprises said N-terminal alpha-helical domain derived from alpha-lactalbumin; and oleic acid or an oleate salt, in a ratio of at least 3 oleic acid or oleate salt molecules per peptide molecule.
When referring to the variant, the specification does not provide any structural attributes.
Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“A definition by function alone “does not suffice” to sufficiently describe a coding sequence because it is only an indication of what the gene does, rather than what it is”).”
In the instant case, the specification fails to describe the amino acids correlating with the required activity.
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad.
The specification fails to provide a representative number of examples for the claimed variant.
The specification teaches only one biologically active complex (i.e. SEQ ID NO: 1).
It is noted that SEQ ID NO: 1 is 39 amino acids long, thus, even considering only natural amino acids, one would end up with 29,640 (39x38x20) possible variants having 94% identity to SEQ ID NO: 1.
If one had to consider the thousands of non-natural amino acids, one would end up with millions of possible variants.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”).
Therefore, since the specification fails to identify any relevant structural characteristics that can be attributed to the claimed function and activity, the claimed invention lacks written description.
Response to Arguments
Applicant’s arguments filed on 6/11/2026 have been fully considered but they are not persuasive.
Applicant argues that “[A]s amended, the claims require that any such variant also comprise the N-terminal alpha-helical domain derived from alpha-lactalbumin. Consequently, the claims are directed to a structurally defined subset of alpha-lactalbumin-derived peptides rather than to all theoretical sequences meeting a percentage-identity threshold”.
Applicant also argues that “[S]tructural studies of human alpha-lactalbumin characterize the N-terminal portion corresponding to SEQ ID NO: 1 as containing multiple helical structural elements. For example, in the 1A4V PDB1 entry for human alpha lactalbumin: 1) positions 5-15 are characterized as a helix; 2) positions 18-20 are characterized as a helix (e.g., a 310 helix); and 3) positions 24-34 are characterized as a helix, which is reproduced below for clarity
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Thus, the amendment does not merely require a degree of sequence identity but instead requires retention of a defined structural feature of the peptide. Variants, including any subject to mutation or substitution, that do not comprise the recited N-terminal alpha-helical domain fall outside the scope of the claims”.
Applicant further argues that “[T]he specification teaches a family of related alpha-lactalbumin-derived peptides and fragments, including SEQ ID NO: 1 and SEQ ID N0:3 (which represents the first 15 amino acids of SEQ ID NO: 1), and further teaches variants of such peptides. Thus, the application does not present a single isolated species and then attempt to claim all possible sequence variants. Rather, it describes a structurally coherent class of alpha-lactalbumin-derived peptides sharing a common N-terminal alpha-helical domain. The amendment transforms the claimed genus from one defined primarily by sequence identity to one defined by sequence identity in combination with a specific structural feature, namely the N-terminal alpha-helical domain derived from alpha-lactalbumin”.
Applicant’s arguments are not persuasive.
The claims as amended require the peptide to comprise an N-terminal alpha helical domain derived from alpha-lactalbumin and SEQ ID NO: 1 or a variant of SEQ ID NO: 1 having at least 94% sequence identity to SEQ ID NO: 1.
Applicant stated that there are 3 N-terminal alpha helical domains (i.e. positions 5-15 (KCELSQLLKDI); positions 18-20 (YGG); and positions 24-34 (PELICTMFHTS).
Therefore, the claimed peptide can comprise:
1) SEQ ID NO: 1 or a variant of SEQ ID NO: 1; and KCELSQLLKDI;
2) SEQ ID NO: 1 or a variant of SEQ ID NO: 1; and YGG;
3) SEQ ID NO: 1 or a variant of SEQ ID NO: 1; and PELICTMFHTS.
As discussed above, one would end up with 29,640 (39x38x20) possible variants having 94% identity to SEQ ID NO: 1, even when considering only natural amino acids.
Applicant has demonstrated that peptide 1 (KQFTKAELSQLLKDI), peptide 10 (AAKKILDIKGIDYWL) and peptide 11 (IDYWLAHKALATEKL) can be uptaken by tumor cells (see Table below from Ho et al. (cited by the Applicant on page 8).
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It is noted that none of the three peptides comprises any of the 3 N-terminal alpha helical domains described by the Applicant.
However, peptide 1, which has been shown to have tumoricidal activity, is comprised in instant SEQ ID NO: 1 (the first 15 residues).
It is clear from the claims and the specification, that Applicant was only in possession of peptides comprising at minimum the first 15 amino acids of SEQ ID NO: 1.
For the reasons stated above the rejection is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This rejection is maintained.
Claims 14, 16 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Svanborg et al. (US 8796218) in view of Iqbal et al. (Therapy (2007) 4(2), 115-117).
Svanborg et al. teach a method for inhibiting the growth of a cancer cell, the method comprising contacting the cancer cell with a biologically active complex comprising a recombinant a-lactalbumin protein, which lacks intra-molecular disulfide bonds, and oleic acid, wherein cysteine residues in native a-lactalbumin have been changed to other amino acid residues in the recombinant protein (claim 16).
Svanborg et al. also teach that the biologically active complex is SEQ ID NO: 1 (claim 8), which comprises instantly claimed SEQ ID NO: 1
Svanborg et al. further teach a pharmaceutical composition comprising the biologically active complex and a pharmaceutically acceptable carrier (claim 12).
Svanborg et al. do not teach the composition comprises another chemotherapeutic agent (i.e. mitomycin C).
Iqbal et al. teach that mitomycin C is used for the treatment of bladder cancer (title; abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that the composition of Svanborg et al. and mitomycin C are effective in treating bladder cancer, it would have been obvious to combine the two with the expectation that such a combination would be effective in treating bladder cancer. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed ratio of oleic acid or oleate salt molecules per peptide molecule, the instant specification teaches that preparation of the biological active complex can be carried out simply by mixing together a suitable peptide and oleic acid or a salt thereof (page 16, 3rd para). Therefore, since Svanborg et al. teach mixing together the claimed peptide and oleic acid, a biologically active complex as claimed would be inherently formed.
This rejection is maintained.
Claims 14, 16 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Svanborg et al. (US 9085643) in view of Iqbal et al. (Therapy (2007) 4(2), 115-117).
Svanborg et al. teach a method for treating a cancer selected from the group consisting of skin papilloma, bladder cancer, glioblastoma, lung cancer, kidney cancer, ovarian cancer, and lymphoma, the method comprising administering to a patient in need thereof a biologically active complex comprising a peptide 20 comprising SEQ ID NO: 3, wherein the peptide is up to 50 amino acids in length, and a fatty acid or lipid salt, or a pharmaceutical composition comprising the biologically active complex (claim 8), wherein the peptide comprises SEQ ID NO: 5 (claim 9), and wherein the fatty acid or lipid is an oleate salt (claim 10).
It is noted that SEQ ID NO: 5 corresponds to instantly claimed SEQ ID NO: 1.
Svanborg et al. further teach a pharmaceutical composition comprising the biologically active complex and a pharmaceutically acceptable carrier (claim 6).
Svanborg et al. do not teach the composition comprises another chemotherapeutic agent (i.e. mitomycin C).
Iqbal et al. teach that mitomycin C is used for the treatment of bladder cancer (title; abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that the composition of Svanborg et al. and mitomycin C are effective in treating bladder cancer, it would have been obvious to combine the two with the expectation that such a combination would be effective in treating bladder cancer. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed ratio of oleic acid or oleate salt molecules per peptide molecule, the instant specification teaches that preparation of the biological active complex can be carried out simply by mixing together a suitable peptide and oleic acid or a salt thereof (page 16, 3rd para). Therefore, since Svanborg et al. teach mixing together the claimed peptide and oleic acid, a biologically active complex as claimed would be inherently formed.
Response to Arguments
Applicant’s arguments filed on 6/11/2026 have been fully considered but they are not persuasive.
Applicant argues that “[t]he Office Action does not dispute that the specification demonstrates a greater-than-additive therapeutic effect for the combination of mitomycin and the alpha-lactalbumin-derived peptide/oleate complex. The primary basis articulated in the Office Action for discounting the acknowledged synergistic effect was alleged lack of commensurateness arising from the construed breadth of the previously pending claims. The present amendment directly addresses the sole articulated basis upon which the Office Action discounted the acknowledged synergistic effect”.
Applicant’s arguments are not persuasive.
As discussed above under “Response to Arguments” on pages 5-7, the claims as amended are not limited to the combination having synergistic effect.
For the reasons stated above the rejection is maintained.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
This rejection is maintained.
Claims 14, 16 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 8796218 in view of Iqbal et al. (Therapy (2007) 4(2), 115-117).
‘218 teaches a method for inhibiting the growth of a cancer cell, the method comprising contacting the cancer cell with a biologically active complex comprising a recombinant a-lactalbumin protein, which lacks intra-molecular disulfide bonds, and oleic acid, wherein cysteine residues in native a-lactalbumin have been changed to other amino acid residues in the recombinant protein (claim 16).
‘218 also teaches that the biologically active complex is SEQ ID NO: 1 (claim 8), which comprises instantly claimed SEQ ID NO: 1
‘218 further teaches a pharmaceutical composition comprising the biologically active complex and a pharmaceutically acceptable carrier (claim 12).
‘218 does not teach the composition comprises another chemotherapeutic agent (i.e. mitomycin C).
Iqbal et al. teach that mitomycin C is used for the treatment of bladder cancer (title; abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that SEQ ID NO: 1 and mitomycin C are effective in treating bladder cancer, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating bladder cancer. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed ratio of oleic acid or oleate salt molecules per peptide molecule, the instant specification teaches that preparation of the biological active complex can be carried out simply by mixing together a suitable peptide and oleic acid or a salt thereof (page 16, 3rd para). Therefore, since Svanborg et al. teach mixing together the claimed peptide and oleic acid, a biologically active complex as claimed would be inherently formed.
Response to Arguments
Applicant’s arguments filed on 6/11/2026 have been fully considered but they are not persuasive.
Applicant arguments have been addressed above under “Response to Arguments” on pages 11-12.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 14, 16 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9085643 in view of Iqbal et al. (Therapy (2007) 4(2), 115-117).
‘643 teaches a method for treating a cancer selected from the group consisting of skin papilloma, bladder cancer, glioblastoma, lung cancer, kidney cancer, ovarian cancer, and lymphoma, the method comprising administering to a patient in need thereof a biologically active complex comprising a peptide 20 comprising SEQ ID NO: 3, wherein the peptide is up to 50 amino acids in length, and a fatty acid or lipid salt, or a pharmaceutical composition comprising the biologically active complex (claim 8), wherein the peptide comprises SEQ ID NO: 5 (claim 9), and wherein the fatty acid or lipid is an oleate salt (claim 10).
It is noted that SEQ ID NO: 5 corresponds to instantly claimed SEQ ID NO: 1.
‘643 further teaches a pharmaceutical composition comprising the biologically active complex and a pharmaceutically acceptable carrier (claim 6).
‘643 does not teach the composition comprises another chemotherapeutic agent (i.e. mitomycin C).
Iqbal et al. teach that mitomycin C is used for the treatment of bladder cancer (title; abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that SEQ ID NO: 1 and mitomycin C are effective in treating bladder cancer, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating bladder cancer. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed ratio of oleic acid or oleate salt molecules per peptide molecule, the instant specification teaches that preparation of the biological active complex can be carried out simply by mixing together a suitable peptide and oleic acid or a salt thereof (page 16, 3rd para). Therefore, since Svanborg et al. teach mixing together the claimed peptide and oleic acid, a biologically active complex as claimed would be inherently formed.
Response to Arguments
Applicant’s arguments filed on 6/11/2026 have been fully considered but they are not persuasive.
Applicant arguments have been addressed above under “Response to Arguments” on pages 11-12.
For the reasons stated above the rejection is maintained.
Allowable Subject Matter
Claims 42-43 and 45-46 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MELISSA FISHER can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
Prosecution Insights