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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 5/23/2025 has been entered.
DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Amendment after Final office action filed on 5/23/2025 is acknowledged.
3. Claims 1-25, 27, 29 and 47 have been cancelled.
4. Claims 26, 28, 30-46 and 48-50 are pending in this application.
5. Claims 46 and 48-50 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims 28 and 32-34 remain withdrawn from consideration as being drawn to non-elected species.
6. Applicant elected without traverse of Group 1 (claims 26-45 and 47) and elected without traverse of SEQ ID NO: 78 as species of cell penetrating carrier peptide; ferrocenecarboxylic acid as species of active ingredient; covalent bond as species of bond to combine the carrier peptide and the active ingredient; and iron-based contrast agent as species of contrast agent in the reply filed on 8/8/2024.
Please note: SEQ ID NO: 78 as the elected species of cell penetrating carrier peptide does not read on instant claims. Therefore, this species would not be searched and examined in the current office action.
Restriction requirement was deemed proper and made FINAL in the previous office actions. Group 1 is drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122. A search was conducted on the elected species; and prior art was found. Claims 28 and 32-34 remain withdrawn from consideration as being drawn to non-elected species. Claims 26, 30, 31 and 35-45 are examined on the merits in this office action.
Claim Interpretations
7. With regards the terms “comprising” and “having” recited in instant claims 26 and 45, the instant specification discloses that “The term "including", "having", "consisting", and "comprising" shall be interpreted openly (i.e. "including but not limited to").” (see pages 30-31, paragraph [0105] of instant specification). Therefore, the instant claimed cell penetrating carrier peptide is one comprising the amino acid sequence of instant SEQ ID NO: 122. Such interpretation applies to all the rejections set forth below.
Withdrawn Objections and Rejections
8. Objection to the drawings is hereby withdrawn in view of Applicant's amendment to the description of the drawings in the specification.
9. Rejection to claims 26, 30, 31, 41-45 and 47 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 of US patent 10888606 B2, and as evidenced by Morris et al (Am J Respir Crit Care Med, 2003, 168, pages 63-69, cited and enclosed in the previous office action) is hereby withdrawn in view of Applicant's amendment to the claim.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 101
10. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
11. (Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 41-45 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 26, 30, 31 and 41-45 are directed to a conjugate, a composition comprising such conjugate, and a cell penetrating carrier peptide.
As evidenced by instant specification, SEQ ID NO: 122 recited in these claims are fragments of human telomerase, which is a naturally occurring protein (see pages 6-12, paragraph [0041] of instant specification). In the broadest reasonable interpretation, the part of telomerase other than the instant claimed SEQ ID NO: 122 is the active ingredient recited in instant claims 26 and 30. Therefore, human telomerase meets all the structural limitations of the instant claimed conjugate, composition comprising such conjugate, and the cell penetrating carrier peptide recited in instant claims 26, 30, 31 and 41-45. And since human telomerase meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, human telomerase would inherently have the same properties and functionality of the peptide recited in instant claim 45. Therefore, human telomerase is a cell penetrating carrier peptide. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
The claims 26, 30, 31 and 41-45 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed conjugate, composition comprising such conjugate, and a cell penetrating carrier peptide in instant claims 26, 30, 31 and 41-45 do not recite features or steps demonstrating a marked difference from what exists in nature; and the claimed conjugate, composition comprising such conjugate, and a cell penetrating carrier peptide in instant claims 26, 30, 31 and 41-45 do not recite meaningful limitations that add something of significance to the judicial exception. Therefore, the claimed conjugate, composition comprising such conjugate, and a cell penetrating carrier peptide in instant claims 26, 30, 31 and 41-45 are not significantly different than a judicial exception (natural product).
Response to Applicant's Arguments
12. Applicant argues that “The amended claims require a peptide having the amino acid sequence of SEQ ID NO: 122, and has markedly different characteristics as compared to the naturally occurring counterpart. Specifically, SEQ ID NO: 122 consists of 11 amino acids, whereas full-length human telomerase is a 1,132-amino-acid protein. The peptide of SEQ ID NO: 122 differs significantly from human telomerase in size, as well as in its N-terminal and C-terminal sequences. As a result, SEQ ID NO: 122 differs from the naturally occurring protein in terms of physicochemical properties such as charge and hydrophobicity, and exhibits a distinct structural profile. SEQ ID NO: 122, as recited in the amended claims, also exhibits functional differences. In particular, SEQ ID NO: 122 demonstrates excellent cell permeability, whereas full-length telomerase lacks efficient intrinsic cell-penetrating capability. Applicants are in the process of preparing a declaration comparing the cell permeability between SEQ ID NO: 122 and full- length telomerase, and plan to submit the same shortly."
13. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about instant rejection:
First, the Examiner would like to point out that there is no declaration filed in instant application.
Second, the Examiner would like to point out that the instant claimed cell penetrating carrier peptide is one comprising a peptide having the amino acid sequence of SEQ ID NO: 122. And as stated in Section 7 above, in view of the disclosure of instant specification, the instant claimed cell penetrating carrier peptide is one comprising the amino acid sequence of instant SEQ ID NO: 122.
Third, as stated in Section 11 above, human telomerase meets all the structural limitations of the instant claimed conjugate, composition comprising such conjugate, and the cell penetrating carrier peptide recited in instant claims 26, 30, 31 and 41-45. Furthermore, since human telomerase meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, human telomerase would inherently have the same properties and functionality of the peptide recited in instant claim 45. Therefore, human telomerase is a cell penetrating carrier peptide. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise. And in the instant case, other than statements/arguments, Applicant fails to provide any data and/or evidence to prove the otherwise. Furthermore, in the event that Applicant provides data and/or evidence to prove human telomerase is not a cell penetrating carrier peptide, instant claims would be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (written description) in the next office action, since the data and/or evidence provided by Applicant indicates not all peptide comprising the amino acid sequence of instant SEQ ID NO: 122 can be a cell penetrating carrier peptide.
Taken all these together, the rejection is deemed proper and is hereby maintained.
Obviousness Double Patenting
14. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
15. (Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 41-45 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US patent 9540419 B2, and as evidenced by Jinap et al (Appetite, 2010, 55, pages 1-10, cited and enclosed in the previous office action).
16. Instant claims 26, 30, 31 and 41-45 are drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122.
17. Claims 1-8 of US patent 9540419 B2 are drawn to a method for treating Alzheimer's disease comprising administering to a subject in need thereof a composition
comprising the isolated peptide of SEQ ID NO: 1.
Claims 1-8 of US patent 9540419 B2 are in possession of a composition
comprising the isolated peptide of SEQ ID NO: 1.
Peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 9540419 B2 consists of the amino acid sequence of EARPALLTSRLRFIPK. It comprises the amino acid sequence of instant SEQ ID NO: 122 (underlined); and it is also a conjugate comprising the cell penetrating carrier peptide of instant SEQ ID NO: 122 (underlined) and the amino acid E. And as evidenced by Jinap et al, Glu (E) is an active ingredient recited in instant claims 26 and 30 (see for example, Title and Abstract).
With regards to the cell penetrating carrier peptide recited in instant claim 45, in the instant case, since the peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 9540419 B2 meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, the peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 9540419 B2 would necessarily have the same properties and functionalities of the cell penetrating carrier peptide recited in instant claim 45. Therefore, the peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 9540419 B2 is a cell penetrating carrier peptide recited in instant claim 45. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Furthermore, with regards to the intended usage limitations recited in instant claims 42-44, in the instant case, the intended use limitations do not patentably distinguish the instant claimed composition from the prior art composition, since such intended use does not create a structural difference between the claimed composition and the prior art composition. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the prior art composition is not capable of preforming the intended use recited in instant claims 42-44. Therefore, the composition recited in claims 1-8 of US patent 9540419 B2 meets the limitations of instant claims 42-44.
18. (Revised due to Applicant’s amendment to the claim) For the same/similar reasoning/rational as the rejection set forth in Sections 15-17 above, instant claims 26, 30, 31 and 41-45 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US patent 9572858 B2; claims 1-16 of US patent 9730984 B2; claims 1-12 of US patent 9844584 B2; claims 1-16 of US patent 9907837 B2; claims 1-16 of US patent 9907838 B2; claims 1-16 of US patent 9937240 B2; claims 1-16 of US patent 10034922 B2; claims 1-9 of US patent 10039811 B2; claims 1-7 of US patent 10383926 B2; claims 1-15 of US patent 10463708 B2; claims 1-20 of US patent 10561703 B2; claims 1-14 of US patent 10662223 B2; claims 1-17 of US patent 10835582 B2; claims 1-6 of US patent 10898540 B2; claims 1-9 of US patent 10960056 B2; claims 1-16 of US patent 10967000 B2; claims 1-6 of US patent 11015179 B2; claims 1-16 of US patent 11058744 B2; claims 1-12 of US patent 11077163 B2; claims 1-9 of US patent 11369665 B2; claims 1-8 of US patent 11857607 B2; claims 1-8 of US patent 12156902 B2; and claims 1-8 of US patent 12168039 B2; and as evidenced by Jinap et al (Appetite, 2010, 55, pages 1-10, cited and enclosed in the previous office action).
19. (Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 35-45 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US patent 11844845 B2.
20. Instant claims 26, 30, 31 and 35-45 are drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122.
21. Claims 1-8 of US patent 11844845 B2 is drawn to a conjugate consisting of a cell penetrating carrier peptide, an active ingredient, and optionally a linker; wherein the carrier peptide is a peptide consisting of any one amino acid sequence of SEQ ID NO: 2 to SEQ ID NO: 9, SEQ ID NO: 11 to SEQ ID NO: 41, and SEQ ID NO: 43 to SEQ ID NO: 77; wherein the conjugate does not comprise the amino acid sequence of telomerase; wherein the carrier peptide and the active ingredient are coupled via a noncovalent bond or a covalent bond; and wherein the active ingredient is a contrast agent.
Each of the cell penetrating carrier peptides of SEQ ID NOs: 2-9, 11-41 and 43-77 recited in claims 1-8 of US patent 11844845 B2 comprises the amino acid sequence of instant SEQ ID NO: 122.
Furthermore, the only active ingredient in the composition recited in instant claim 41 is the conjugate recited in instant claim 26.
In addition, with regards to the intended usage limitations recited in instant claims 42-44, in the instant case, the intended use limitations do not patentably distinguish the instant claimed composition from the prior art composition, since such intended use does not create a structural difference between the claimed composition and the prior art composition. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the prior art composition is not capable of preforming the intended use recited in instant claims 42-44. Therefore, the conjugate recited in claims 1-8 of US patent 11844845 B2 meets the limitations of instant claims 42-44.
22. (Revised due to Applicant’s amendment to the claim) For the same/similar reasoning/rational as the rejection set forth in Sections 19-21 above, instant claims 26, 30, 31 and 35-45 remain provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 28-41 and 45-47 of co-pending Application No. 18/451280.
In the instant case, the cell penetrating carrier peptide of SEQ ID NO: 133 recited in claims 28-41 and 45-47 of co-pending Application No. 18/451280 comprises the amino acid sequence of instant SEQ ID NO: 122.
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Response to Applicant's Arguments
23. Applicant argues that “the claims of the reference patents or patent applications do not teach or suggest the features of the amended claims which require a peptide having the amino acid sequence of SEQ ID NO: 122."
24. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about these ODP rejections, the Examiner would like to point out that the instant claimed cell penetrating carrier peptide is one comprising a peptide having the amino acid sequence of SEQ ID NO: 122. And as stated in Section 7 above, in view of the disclosure of instant specification, the instant claimed cell penetrating carrier peptide is one comprising the amino acid sequence of instant SEQ ID NO: 122. And in the instant case, the peptides recited in claims of all these ODP rejections comprise the amino acid sequence of instant SEQ ID NO: 122. Therefore, it is unclear to the Examiner on what Applicant’s arguments are based. Further clarification is required.
Taken all these together, these rejections are deemed proper. And until a proper terminal disclaimer is filed and approved by the Office, these double patenting rejections are hereby maintained.
Claim Rejections - 35 U.S.C. § 102
25. 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.
26. Please note: during the search for the elected species, prior art was found for the non-elected species of active ingredient.
(Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 41-45 remain rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Brunsvig et al (Cancer Immunol Immunother, 2006, 55, pages 1553-1564, cited and enclosed in the previous office action), and as evidenced by Jinap et al (Appetite, 2010, 55, pages 1-10, cited and enclosed in the previous office action).
The instant claims 26, 30, 31 and 41-45 are drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122.
Brunsvig et al teach GV1001 peptide consisting of the amino acid sequence EARPALLTSRLRFIPK; and a vaccine composition comprising the GV1001 peptide, for example, page 1555, right column, Section “Vaccine and control peptides”. The GV1001 peptide in Brunsvig et al is a conjugate comprising the peptide of instant SEQ ID NO: 122 (underlined) and E. And as evidenced by Jinap et al, Glu (E) is an active ingredient recited in instant claims 26 and 30 (see for example, Title and Abstract). It reads on covalent bond as the elected species of bond to combine the carrier peptide and the active ingredient. It meets the limitations of instant claims 26, 30, 31 and 41.
With regards to the cell penetrating carrier peptide recited in instant claim 45, in the instant case, since the GV1001 peptide in Brunsvig et al meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, the GV1001 peptide in Brunsvig et al would necessarily have the same properties and functionalities of the cell penetrating carrier peptide recited in instant claim 45. Therefore, the GV1001 peptide in Brunsvig et al is a cell penetrating carrier peptide recited in instant claim 45. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Furthermore, with regards to the intended usage limitations recited in instant claims 42-44, in the instant case, the intended use limitations do not patentably distinguish the instant claimed composition from the prior art composition, since such intended use does not create a structural difference between the claimed composition and the prior art composition. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the prior art composition is not capable of preforming the intended use recited in instant claims 42-44. Therefore, the GV1001 peptide in Brunsvig et al as a composition meets the limitations of instant claims 42-44.
Since the reference teaches all the limitations of instant claims 26, 30, 31 and 41-45; the reference anticipates instant claims 26, 30, 31 and 41-45.
27. Please note: during the search for the elected species, prior art was found for the non-elected species of active ingredient.
(Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 41-45 remain rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Counter et al (Oncogene, 1998, 16, pages 1217-1222, filed with IDS), and as evidenced by the Telomerase catalytic subunit-synthetic construct document (pages 1-2, from https://www.ncbi.nlm.nih.gov/, 9/15/2005, filed with IDS).
The instant claims 26, 30, 31 and 41-45 are drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122.
Counter et al, throughout the literature, teach the important roles of telomerase played in maintaining telomere length with each cell division cycle; and a fusion protein hTERT-HA comprising human telomerase reverse transcriptase (hTERT) and an influenza virus hemagglutinin (HA) epitope tag, for example, page 1217, the 1st paragraph; and page 1219, left column, the 3rd paragraph. And as evidenced by the Telomerase catalytic subunit-synthetic construct document, the fusion protein hTERT-HA in Counter et al comprises a peptide consisting of the amino acid sequence of instant SEQ ID NO: 122 recited in instant claim 26. In the broadest reasonable interpretation, the part of the fusion protein hTERT-HA other than the instant claimed SEQ ID NO: 122 is the active ingredient recited in instant claims 26 and 30. Therefore, the fusion protein hTERT-HA in Counter et al reads on covalent bond as the elected species of bond to combine the carrier peptide and the active ingredient. It meets the limitations of the conjugate recited in instant claims 26, 30 and 31; and the composition recited in instant claim 41.
With regards to the cell penetrating carrier peptide recited in instant claim 45, in the instant case, since the fusion protein hTERT-HA in Counter et al meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, the fusion protein hTERT-HA in Counter et al would necessarily have the same properties and functionalities of the cell penetrating carrier peptide recited in instant claim 45. Therefore, the fusion protein hTERT-HA in Counter et al is a cell penetrating carrier peptide recited in instant claim 45. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Furthermore, with regards to the intended usage limitations recited in instant claims 42-44, in the instant case, the intended use limitations do not patentably distinguish the instant claimed composition and/or contrast agent from the prior art composition and/or contrast agent, since such intended use does not create a structural difference between the claimed composition and/or contrast agent and the prior art composition and/or contrast agent. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the prior art composition is not capable of preforming the intended use recited in instant claims 42-44. Therefore, the fusion protein hTERT-HA in Counter et al meets the limitations of instant claims 42-44.
Since the reference teaches all the limitations of instant claims 26, 30, 31 and 41-45; the reference anticipates instant claims 26, 30, 31 and 41-45.
Response to Applicant's Arguments
28. Applicant argues that “(1) The amended claims require a peptide having the amino acid sequence of SEQ ID NO: 122 which is not taught by the cited references. Therefore, the amended claims are not anticipated by the cited references.”; and “(2) In addition, the amended claims would not have been obvious over the cited references, even if those references are considered in evaluating obviousness rejections."
29. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about instant rejections, the Examiner would like to point out that as stated in Section 7 above, in view of the disclosure of instant specification, the instant claimed cell penetrating carrier peptide is one comprising the amino acid sequence of instant SEQ ID NO: 122. Therefore, the instant claimed cell penetrating carrier peptide is taught by the cited prior art references. Furthermore, the rejections set forth in Sections 26 and 27 above are rejections under pre-AIA 35 U.S.C. 102(b) (anticipation), not rejections under pre-AIA 35 U.S.C. 103(a). Therefore, Applicant’s arguments that “(2) In addition, the amended claims would not have been obvious over the cited references, even if those references are considered in evaluating obviousness rejections." are irrelevant to instant rejections.
Taken all these together, these rejections are deemed proper and are hereby maintained.
Claim Rejections - 35 U.S.C. § 103
30. 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 of this title, 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 negatived by the manner in which the invention was made.
31. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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.
32. (Revised due to Applicant’s amendment to the claim) Claims 26, 30, 31 and 35-45 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Counter et al (Oncogene, 1998, 16, pages 1217-1222, filed with IDS), and as evidenced by the Telomerase catalytic subunit-synthetic construct document (pages 1-2, from https://www.ncbi.nlm.nih.gov/, 9/15/2005, filed with IDS), and further in view of Seiwert et al (J Am Soc Mass Spectrom, 2008, 19, pages 1-7, filed with IDS).
The instant claims 26, 30, 31 and 35-45 are drawn to a conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the carrier peptide comprises a peptide having the amino acid sequence of SEQ ID NO: 122; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient; and a cell penetrating carrier peptide comprising a peptide having the amino acid sequence of SEQ ID NO: 122.
Please note: For the purpose of this examination and in the broadest reasonable interpretation, the Examiner is interpreting the carboxylic acid group in either ferrocenecarboxylic acid as the elected species of active ingredient or ferrocene carboxylate recited in instant claim 37 can be one reacted with other group in the conjugate.
Counter et al, throughout the literature, teach the important roles of telomerase played in maintaining telomere length with each cell division cycle; and a fusion protein hTERT-HA comprising human telomerase reverse transcriptase (hTERT) and an influenza virus hemagglutinin (HA) epitope tag, for example, page 1217, the 1st paragraph; and page 1219, left column, the 3rd paragraph. And as evidenced by the Telomerase catalytic subunit-synthetic construct document, the fusion protein hTERT-HA in Counter et al comprises a peptide consisting of the amino acid sequence of instant SEQ ID NO: 122 recited in instant claim 26. In the broadest reasonable interpretation, the part of the fusion protein hTERT-HA other than the instant claimed SEQ ID NO: 122 is the active ingredient recited in instant claims 26 and 30. Therefore, the fusion protein hTERT-HA in Counter et al reads on covalent bond as the elected species of bond to combine the carrier peptide and the active ingredient. It meets the limitations of the conjugate recited in instant claims 26, 30 and 31; and the composition recited in instant claim 41.
With regards to the cell penetrating carrier peptide recited in instant claim 45, in the instant case, since the fusion protein hTERT-HA in Counter et al meets all the structural limitations of the cell penetrating carrier peptide recited in instant claim 45, the fusion protein hTERT-HA in Counter et al would necessarily have the same properties and functionalities of the cell penetrating carrier peptide recited in instant claim 45. Therefore, the fusion protein hTERT-HA in Counter et al is a cell penetrating carrier peptide recited in instant claim 45. And the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). Since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Furthermore, with regards to the intended usage limitations recited in instant claims 42-44, in the instant case, the intended use limitations do not patentably distinguish the instant claimed composition and/or contrast agent from the prior art composition and/or contrast agent, since such intended use does not create a structural difference between the claimed composition and/or contrast agent and the prior art composition and/or contrast agent. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the prior art composition is not capable of preforming the intended use recited in instant claims 42-44. Therefore, the fusion protein hTERT-HA in Counter et al meets the limitations of instant claims 42-44.
The difference between the reference and instant claims 26, 30, 31 and 35-45 is that the reference does not teach ferrocenecarboxylic acid as the elected species of active ingredient; iron-based contrast agent as the elected species of contrast agent; and the limitations of instant claims 35-40.
However, Seiwert et al, throughout the literature, teach a method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins, wherein the method is based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents N-(2-ferroceneethyl)maleimide (FEM) and ferrocenecarboxylic acid-(2-maleimidoyl)ethylamide (FMEA), for example, Abstract. Seiwert et al further teach the determination of the number and position of both bound and free cysteine residues provides important information allowing the understanding of protein structure and function, for example, page 1, left column, the 1st paragraph.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Counter et al and Seiwert et al to develop a conjugate comprising hTERT-HA covalently linked to FEM or FMEA; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient. Ingredient; and a cell penetrating carrier peptide comprising the amino acid sequence of instant SEQ ID NO: 122. It reads on ferrocenecarboxylic acid as the elected species of active ingredient; and iron-based contrast agent as the elected species of contrast agent.
Furthermore, with regards to the intended usage limitations recited in instant claims 39 and 40, in the instant case, the intended use limitations do not patentably distinguish the instant claimed contrast agent from the prior art contrast agent, since such intended use does not create a structural difference between the claimed contrast agent and the prior art contrast agent. In order to be limiting, 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 (see MPEP § 2111.02). In the instant case, there is no evidence that the conjugate and/or contrast agent developed from the combined teachings of Counter et al and Seiwert et al is not capable of preforming the intended use recited in instant claims 39 and 40. Therefore, the conjugate and/or contrast agent developed from the combined teachings of Counter et al and Seiwert et al meets the limitations of instant claims 39 and 40.
One of ordinary skilled in the art would have been motivated to combine the teachings of Counter et al and Seiwert et al to develop a conjugate comprising hTERT-HA covalently linked to FEM or FMEA; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient. Ingredient; and a cell penetrating carrier peptide comprising the amino acid sequence of instant SEQ ID NO: 122, because Seiwert et al, throughout the literature, teach a method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins, wherein the method is based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents N-(2-ferroceneethyl)maleimide (FEM) and ferrocenecarboxylic acid-(2-maleimidoyl)ethylamide (FMEA). Seiwert et al further teach the determination of the number and position of both bound and free cysteine residues provides important information allowing the understanding of protein structure and function.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Counter et al and Seiwert et al to develop a conjugate comprising hTERT-HA covalently linked to FEM or FMEA; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient. Ingredient; and a cell penetrating carrier peptide comprising the amino acid sequence of instant SEQ ID NO: 122.
Response to Applicant's Arguments
33. Applicant argues that “The amended claims require a peptide having the amino acid sequence of SEQ ID NO: 122 which is different from the full-length hTERT disclosed in Counter. One skilled in the art would not have recognized this highly specific 11-amino-acid fragment, derived from but not identical to full-length hTERT, let alone have had a motivation to combine it with the analytical ferrocenyl reagent disclosed in Seiwert for the purpose of intracellular delivery as a contrast agent or other active compound.”; “Furthermore, as discussed above, SEQ ID NO: 122 demonstrates unexpectedly superior cell permeability compared to the prior art peptide GV1001. The conjugate of such an advanced CPP with ferrocenecarboxylic acid, as in the present disclosure, yields a synergistic effect or novel utility that could not have been predicted from a mere combination of known components. This supports the absence of a reasonable expectation of success.”; and “Seiwert merely discloses a chemical labeling method for the analysis of cysteine residues and does not suggest or teach the conjugation of its reagent with a specific, highly permeable CPP fragment, nor any resulting enhancement in imaging or therapeutic efficacy."
34. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about instant rejection, the Examiner agrees that none of the cited references individually teaches or suggests the products recited in instant claims 26, 30, 31 and 35-45; and none of the cited references anticipates the products recited in instant claims 26, 30, 31 and 35-45. However, the Examiner would like to point out that instant claims 26, 30, 31 and 35-45 are rejected under pre-AIA 35 U.S.C. 103(a) (obviousness type), and the rejection is based on the combined teachings of Counter et al and Seiwert et al; therefore, it is not necessary for each of the cited references to teach all the limitations of instant claims. Furthermore, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
In response to Applicant’s arguments about the instant claimed cell penetrating carrier peptide, the Examiner would like to point out that as stated in Section 7 above, in view of the disclosure of instant specification, the instant claimed cell penetrating carrier peptide is one comprising the amino acid sequence of instant SEQ ID NO: 122. Therefore, the full-length hTERT disclosed in Counter et al meets all the structural limitations of the instant claimed cell penetrating carrier peptide.
In response to Applicant’s arguments that “SEQ ID NO: 122 demonstrates unexpectedly superior cell permeability compared to the prior art peptide GV1001”, the Examiner would like to bring Applicant’s attention to MPEP § 716.02, which provides the guidelines about allegations of unexpected results. And in the instant case, GV1001 is not the peptide disclosed in the closest prior art (Counter et al) cited in instant rejection.
In response to Applicant’s arguments about motivation to combined the cited prior art reference and reasonable expectation of success, in the instant case, in view of the combined teachings of the cited prior art references as set forth in Section 32 above, one of ordinary skilled in the art would have been motivated, and/or a person of ordinary skilled in the art would have reasonable expectation of success to develop a conjugate comprising hTERT-HA covalently linked to FEM or FMEA; a contrast agent comprising such conjugate; a composition comprising such conjugate as an active ingredient. Ingredient; and a cell penetrating carrier peptide comprising the amino acid sequence of instant SEQ ID NO: 122. Furthermore, with regards to the expectation of success, the MPEP states: “Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. The Federal Circuit concluded that “[g]ood science and useful contributions do not necessarily result in patentability.” Id. at 1364, 83 USPQ2d at 1304.” (see MPEP § 2145).
Taken all these together, the rejection is deemed proper and is hereby maintained.
New Objections
35. Claim 26 is objected to for the following minor informality: Applicant is suggested to amend claim 26 as “A conjugate comprising a cell penetrating carrier peptide and an active ingredient, wherein the cell penetrating carrier peptide comprises the amino acid sequence of SEQ ID NO: 122”.
36. Claim 45 is objected to for the following minor informality: Applicant is suggested to amend claim 45 as “A cell penetrating carrier peptide comprising the amino acid sequence of SEQ ID NO: 122”.
New Rejections
Obviousness Double Patenting
37. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
38. For the same/similar reasoning/rational as the rejection set forth in Sections 15-17 above, instant claims 26, 30, 31 and 35-45 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 of co-pending Application No. 19/115927, and as evidenced by Jinap et al (Appetite, 2010, 55, pages 1-10, cited and enclosed in the previous office action).
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Conclusion
No claim is allowed.
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