DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the cited rejections will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
3. Response to Election/Restriction filed on 3/9/2026 is acknowledged.
4. Claim filed on 3/9/2026 is acknowledged.
5. Claims 1-168 and 188 have been cancelled.
6. Claims 169-187 are pending in this application.
7. Claims 176-187 are withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims 172-174 are withdrawn from consideration as being drawn to non-elected species.
8. Claims 169-171 and 175 are under examination.
Priority
9. The application is a 371 of PCT/IB2021/000786 filed on 11/18/2021, which claim priority to US provisional application No. 63/115208 filed on 11/18/2020. US provisional application No. 63/115208 provides support to instant claims 169-171 and 175. Therefore, the effective filing date of instant claims instant claims 169-171 and 175 is 11/18/2020.
Election/Restrictions
10. Applicant’s election without traverse of Group 2 (claims 169-175) and election without traverse of a EPO molecule comprising an Fc domain of IgG indirectly fused to the C-terminus of instant SEQ ID NO: 21 and having reduced immunogenicity in a subject as species of EPO molecule in the reply filed on 3/9/2026 is acknowledged. Since the elected species of EPO molecule is a subgenus, not a species; the Examiner telephoned Applicant’s representative, David Lu, for further species election. And Applicant’s representative elected on the phone that an EPO molecule consisting of SEQ ID NO: 21 as species of EPO molecule on 3/13/2026. The requirement is made FINAL in this office action.
Group 2 is drawn to an erythropoietin (EPO) molecule comprising a mutation at one or more positions of SEQ ID NO: 1, wherein the EPO molecule comprises: (a) a mutation at a position corresponding to position 74 of SEQ ID NO: 1, wherein the mutation is a V74D substitution; (b) a mutation at a position corresponding to position 106 of SEQ ID NO: 1, wherein the mutation is a T106G substitution or the mutation is a T106H substitution; (c) mutations at positions corresponding to positions 67 and 102 of SEQ ID NO: 1, wherein the mutations are L67V and L102V substitutions; (d) mutations at positions corresponding to positions 70, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L70V, V74L, and L102I substitutions; (e) mutations at positions corresponding to positions 67, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L67N, V74N, and L102D substitutions or the mutations are L67D, V74D, and L102N substitutions; (f) mutations at positions corresponding to positions 12, 15, 105, and 149 of SEQ ID NO: 1, wherein the mutations are L12A, Y15I, L105F, and L149W substitutions or the mutations are L12I,Y15W, L105S, and L149V substitutions; (g) mutations at positions corresponding to positions 109 and 114 of SEQ ID NO: 1, wherein the mutations are L109C and A114C substitutions; or (h) mutations at positions corresponding to positions 102, 105, 106, and 109 of SEQ ID NO: 1, wherein the mutations are L102T, L105S, T106H, and L109W substitutions or the mutations are L102T, L105S, T106G, and L109W substitutions; and a pharmaceutical composition comprising such EPO molecule and a pharmaceutically acceptable carrier. A search was conducted on the elected species; and this appears to be free of prior art. A search was extended to the genus in claim 169; and prior art was found. Claims 172-174 are withdrawn from consideration as being drawn to non-elected species. Claims 169-171 and 175 are examined on the merits in this office action.
Objections
11. The specification is objected to for the following minor informality: The specification recites various hyperlinks throughout the specification, for example, page 23, lines 20 and 24; page 24, line 5; and page 70, lines 33-34 of instant specification. The embedded hyperlinks and/or other forms of browser-executable code are impermissible and require deletion. It is suggested that Applicant places a URL between these symbols “< >” to inactivate the hyperlinks. Applicant is required to correct these errors.
Please note: The specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
12. The drawings are objected to for the following minor informality:
Figure 1A: The description of Fig. 1A indicates part of the amino acid sequence is shaded. However, it is unclear which part of the amino acid sequence in instant Fig. 1A is shaded.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
13. Claim 169 is objected to for the following minor informality: Applicant is suggested to amend claim 169 as “An erythropoietin (EPO) molecule comprising a mutation at one or more positions of SEQ ID NO: 1 selected from: (a) V74D substitution; (b) T106G or T106H substitution; (c) a combination of L67V and L102V substitutions; (d) a combination of L70V, V74L, and L102I substitutions; (e) a combination of L67N, V74N, and L102D substitutions or a combination of L67D, V74D, and L102N substitutions; (f) a combination of L12A, Y15I, L105F, and L149W substitutions or a combination of L12I, Y15W, L105S, and L149V substitutions; (g) a combination of L109C and A114C substitutions; or (h) a combination of L102T, L105S, T106H, and L109W substitutions or a combination of L102T, L105S, T106G, and L109W substitutions”.
14. Claim 170 is objected to for the following minor informality: Applicant is suggested to amend claim 170 as “The EPO molecule of claim 169, wherein the EPO molecule comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 31, or SEQ ID NO: 33".
15. Claim 171 is objected to for the following minor informality: Applicant is suggested to amend claim 171 as “The EPO molecule of claim 169, wherein in comparison to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1, the EPO molecule: (a) has a reduced immunogenicity in a subject; (b) has the same biological activity; (c) has a biological activity that is reduced by no more than 25%; (d) is capable of having more glycoforms; (e) has the same serum half-life; (f) has an increased serum half-life; or (g) has a reduced serum half-life”.
Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (b)
16. The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
17. Claim 171 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
18. Claim 171 recites the limitations “(b) the EPO molecule has the same, or substantially the same, biological activity, as compared to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1”; and “(e) the EPO molecule has the same, or substantially the same, serum half-life, as compared to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1”. With regards to the term “substantially the same”, the instant specification fails to define it. Therefore, it is unclear what is encompassed within the recited “substantially the same”. Thus, the metes and bounds of instant claim 171 is vague and indefinite.
Claim Rejections - 35 U.S.C. § 112 paragraph (d)
19. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
20. Claim 171 is rejected under 35 U.S.C. 112(d) or 35 U.S.C. 112 (pre-AIA ), 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
21. Claim 171 depends on claim 169; and claim 171 recites “The EPO molecule of claim 169, wherein:…(e) the EPO molecule has the same, or substantially the same, serum half-life, as compared to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1; (f) the EPO molecule has an increased serum half-life as compared to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1; or (g) the EPO molecule has a reduced serum half-life as compared to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1”. However, in comparison to a reference EPO molecule comprising the amino acid sequence of SEQ ID NO: 1, the EPO molecule in claim 169 can only has the same, increased or reduced serum half-life. Therefore, the scope of the EPO molecule recited in instant claim 171 is identical to that of the EPO molecule recited in instant claim 169. Claim 171 does not further limit the scope of the EPO molecule in claim 169; therefore, claim 171 is improper dependent forms for failing to further limit the subject matter of claim 169.
Claim Rejections - 35 U.S.C. § 102(a)(1)
22. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
23. Claims 169, 171 and 175 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guyon et al (US 2012/0094906 A1).
The instant claims 169, 171 and 175 are drawn to an erythropoietin (EPO) molecule comprising a mutation at one or more positions of SEQ ID NO: 1, wherein the EPO molecule comprises: (a) a mutation at a position corresponding to position 74 of SEQ ID NO: 1, wherein the mutation is a V74D substitution; (b) a mutation at a position corresponding to position 106 of SEQ ID NO: 1, wherein the mutation is a T106G substitution or the mutation is a T106H substitution; (c) mutations at positions corresponding to positions 67 and 102 of SEQ ID NO: 1, wherein the mutations are L67V and L102V substitutions; (d) mutations at positions corresponding to positions 70, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L70V, V74L, and L102I substitutions; (e) mutations at positions corresponding to positions 67, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L67N, V74N, and L102D substitutions or the mutations are L67D, V74D, and L102N substitutions; (f) mutations at positions corresponding to positions 12, 15, 105, and 149 of SEQ ID NO: 1, wherein the mutations are L12A, Y15I, L105F, and L149W substitutions or the mutations are L12I,Y15W, L105S, and L149V substitutions; (g) mutations at positions corresponding to positions 109 and 114 of SEQ ID NO: 1, wherein the mutations are L109C and A114C substitutions; or (h) mutations at positions corresponding to positions 102, 105, 106, and 109 of SEQ ID NO: 1, wherein the mutations are L102T, L105S, T106H, and L109W substitutions or the mutations are L102T, L105S, T106G, and L109W substitutions; and a pharmaceutical composition comprising such EPO molecule and a pharmaceutically acceptable carrier.
Guyon et al, throughout the patent, teach modified erythropoietin (EPO) polypeptides; and a pharmaceutical composition comprising such modified EPO polypeptide and a pharmaceutically acceptable carrier, for example, Abstract; and page 67, paragraph [0580]. It meets the limitation of “a pharmaceutically acceptable carrier” recited in instant claim 175. Guyon et al further teach modified EPO polypeptide having a V74D substitution of EPO polypeptide of SEQ ID NO: 2 or 237, wherein such modified EPO polypeptide has reduced immunogenicity, and wherein the EPO polypeptide of SEQ ID NO: 2 is identical to the EPO molecule of instant SEQ ID NO: 1, for example, pages 32-33, Table 4; and SEQ ID NO: 2 in the "Sequence Listing" available in http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20120094906A1. It meets the limitations of the EPO molecule recited in instant claims 169 and 171.
Furthermore, the MPEP states the following: A genus does not always anticipate a claim to a species within the genus. However, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (see MPEP § 2131.02).
Since the reference teaches all the limitations of instant claims 169, 171 and 175; the reference anticipates instant claims 169, 171 and 175.
Claim Rejections - 35 U.S.C. § 103
24. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
25. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
26. Claims 169-171 and 175 are rejected under 35 U.S.C. 103 as being unpatentable over Guyon et al (US 2012/0094906 A1).
The instant claims 169-171 and 175 are drawn to an erythropoietin (EPO) molecule comprising a mutation at one or more positions of SEQ ID NO: 1, wherein the EPO molecule comprises: (a) a mutation at a position corresponding to position 74 of SEQ ID NO: 1, wherein the mutation is a V74D substitution; (b) a mutation at a position corresponding to position 106 of SEQ ID NO: 1, wherein the mutation is a T106G substitution or the mutation is a T106H substitution; (c) mutations at positions corresponding to positions 67 and 102 of SEQ ID NO: 1, wherein the mutations are L67V and L102V substitutions; (d) mutations at positions corresponding to positions 70, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L70V, V74L, and L102I substitutions; (e) mutations at positions corresponding to positions 67, 74, and 102 of SEQ ID NO: 1, wherein the mutations are L67N, V74N, and L102D substitutions or the mutations are L67D, V74D, and L102N substitutions; (f) mutations at positions corresponding to positions 12, 15, 105, and 149 of SEQ ID NO: 1, wherein the mutations are L12A, Y15I, L105F, and L149W substitutions or the mutations are L12I,Y15W, L105S, and L149V substitutions; (g) mutations at positions corresponding to positions 109 and 114 of SEQ ID NO: 1, wherein the mutations are L109C and A114C substitutions; or (h) mutations at positions corresponding to positions 102, 105, 106, and 109 of SEQ ID NO: 1, wherein the mutations are L102T, L105S, T106H, and L109W substitutions or the mutations are L102T, L105S, T106G, and L109W substitutions; and a pharmaceutical composition comprising such EPO molecule and a pharmaceutically acceptable carrier.
Guyon et al, throughout the patent, teach modified erythropoietin (EPO) polypeptides; and a pharmaceutical composition comprising such modified EPO polypeptide and a pharmaceutically acceptable carrier, for example, Abstract; and page 67, paragraph [0580]. It meets the limitation of “a pharmaceutically acceptable carrier” recited in instant claim 175. Guyon et al further teach modified EPO polypeptide having a V74D substitution of EPO polypeptide of SEQ ID NO: 2 or 237, wherein such modified EPO polypeptide has reduced immunogenicity, and wherein the EPO polypeptide of SEQ ID NO: 2 is identical to the EPO molecule of instant SEQ ID NO: 1, for example, pages 32-33, Table 4; and SEQ ID NO: 2 in the "Sequence Listing" available in http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20120094906A1. It meets the limitations of the EPO molecule recited in instant claims 169 and 171.
The difference between the reference and instant claims 169-171 and 175 is that the reference does not explicilty teach the limitation of instant claim 170.
However, Guyon et al teach modified erythropoietin (EPO) polypeptide comprising: one or more amino acid modifications at masked is-Hit residues masked by different glycosylation sites selected from among amino acid modifications R14H, L67V and many others corresponding to residues in an unmodified EPO polypeptide having the sequence of amino acids set forth in SEQ ID NO: 2 or SEQ ID NO: 237; and one or more additional amino acid modification(s) at an un-masked is-Hit residue selected from among amino acid modifications P2A, L102V and many others corresponding to residues in an unmodified EPO polypeptide having the sequence of amino acids set forth in SEQ ID NO: 2 or SEQ ID NO: 237, for example, claim 1. Guyon et al further teach EPO polypeptide of SEQ ID NO: 2 or 237 with L67V substitution exhibits decreased immunogenicity; and EPO polypeptide of SEQ ID NO: 2 or 237 with L102V substitution exhibits increased protease resistant, for example, pages 32-33, Table 4; and page 79, Table 20.
Therefore, in view of the teachings of Guyon et al as a whole, it would have been obvious to one of ordinary skilled in the art to develop a modified EPO polypeptide with L67V/L102V substitutions in the EPO polypeptide of SEQ ID NO: 2, wherein the modified EPO polypeptide exhibits decreased immunogenicity and increased protease resistant; and a pharmaceutical composition comprising such modified EPO polypeptide and a pharmaceutically acceptable carrier. The modified EPO polypeptide with L67V/L102V substitutions in the EPO polypeptide of SEQ ID NO: 2 is identical to the EPO molecule of instant SEQ ID NO: 3.
In view of the teachings of Guyon et al as a whole, one of ordinary skilled in the art would have been motivated to develop a modified EPO polypeptide with L67V/L102V substitutions in the EPO polypeptide of SEQ ID NO: 2, wherein the modified EPO polypeptide exhibits decreased immunogenicity and increased protease resistant; and a pharmaceutical composition comprising such modified EPO polypeptide and a pharmaceutically acceptable carrier, because Guyon et al teach modified erythropoietin (EPO) polypeptide comprising: one or more amino acid modifications at masked is-Hit residues masked by different glycosylation sites selected from among amino acid modifications R14H, L67V and many others corresponding to residues in an unmodified EPO polypeptide having the sequence of amino acids set forth in SEQ ID NO: 2 or SEQ ID NO: 237; and one or more additional amino acid modification(s) at an un-masked is-Hit residue selected from among amino acid modifications P2A, L102V and many others corresponding to residues in an unmodified EPO polypeptide having the sequence of amino acids set forth in SEQ ID NO: 2 or SEQ ID NO: 237. Guyon et al further teach EPO polypeptide of SEQ ID NO: 2 or 237 with L67V substitution exhibits decreased immunogenicity; and EPO polypeptide of SEQ ID NO: 2 or 237 with L102V substitution exhibits increased protease resistant. The modified EPO polypeptide developed above is Combining Prior Art Elements According to Known Methods To Yield Predictable Results (see MPEP § 2143 I A).
In view of the teachings of Guyon et al as a whole, a person of ordinary skilled in the art would have reasonable expectation of success in developing a modified EPO polypeptide with L67V/L102V substitutions in the EPO polypeptide of SEQ ID NO: 2, wherein the modified EPO polypeptide exhibits decreased immunogenicity and increased protease resistant; and a pharmaceutical composition comprising such modified EPO polypeptide and a pharmaceutically acceptable carrier.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LI N KOMATSU whose telephone number is (571)270-3534. The examiner can normally be reached Mon-Fri 8am-4pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 5712707430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LI N KOMATSU/Primary Examiner, Art Unit 1658
Prosecution Insights