DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments, and/or Claims
2. The Preliminary Amendment filed on 03 December 2024 has been entered in full. Claims 1 and 6-20 have been amended and claims 2-5 and 21 have been cancelled. Therefore, claims 1 and 6-20 are pending and the subject of this Office Action.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 03 December 2024 has been considered by the Examiner.
Specification
4. The disclosure is objected to because of the following informalities: Page 79, line 2 of the Specification recites “administered at 10 □g per day”. Applicant is requested to correct any additional errors which they may make aware of.
Appropriate correction is required.
Claim Objections
5. Claim 9 is objected to because it discloses amino acid sequences without an accompanying sequence identifier (i.e., SEQ ID NO: #). 37 CFR 1.821(d) requires that: Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing," in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), preceded by "SEQ ID NO:" or the like, in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
Furthermore, if the sequences are not present in the sequence listing, Applicant is required to provide (1) a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, (2) a substitute paper copy of that “Sequence Listing”, (3) an amendment directing the entry of that paper into the specification, and (4) a statement that the content of the paper and computer readable copies are the same, and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 through 1.825. The claims and/or instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (i.e., SEQ ID NO: #) be made in the specification and claims wherever a reference is made to that sequence (See M.P.E.P. 2422.04). It is noted that Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing XML." See 37 CFR 1.831(c).
Claim Rejections - 35 USC § 112(b)
6. 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.
7. Claim 1 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.
8. Claim 1 is rejected as being indefinite because there is no step relating back to the preamble, such that there is no correlation between the preamble of “inhibiting cerebral inflammation” and the “subject”. Amending the claim to recite, for example. “A method of inhibiting cerebral inflammation in a subject, comprising administering a CCR5 inhibitor to a subject in need thereof” or “A method of inhibiting cerebral inflammation in a subject in need thereof, comprising administering a CCR5 inhibitor to the subject” would be remedial.
Claim Rejections - 35 USC § 112 (Scope of Enablement)
9. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
10. Claims 1 and 6-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ) because the specification, because the specification, while being enabling for a method of treating or reducing cerebral inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a CCR5 inhibitor, does not reasonably provide enablement for a method of treating or preventing the scope of cerebral inflammation encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
11. The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
12. The claims are drawn quite broadly to a method for inhibiting cerebral inflammation, comprising administering a CCR5 inhibitor to a subject. The claims also recite wherein the subject suffers from or is susceptible to a neuroinflammatory disorder that involves cerebral inflammation (See also 112(b) rejections supra).
13. While the Specification provides an enabling disclosure for methods of treating or inhibiting cerebral inflammation in a subject in need thereof, there is insufficient guidance and a lack of working examples to support a conclusion that the use of a CCR5 inhibitor could be used to treat and/or prevent cerebral inflammation in the subject population encompassed by the scope of the claims.
14. It is well-known in the art that cerebral inflammation is complex and the disease states associated with cerebral inflammation are broad and diverse. For example, Moganti-Kossmann et al teach that neuroinflammation occurring after traumatic brain injury (TBI) is a complex phenomenon comprising distinct cellular and molecular events involving the injured as well as the healthy cerebral tissue, and the exact function of each mediator, activated cell types or pathophysiological mechanism, needs to be further elucidated. (See Moganti-Kossmann et al. Shock. 16(3):165-177, published 2001; cited by Applicant). Accordingly, treatment of cerebral inflammation in an undefined subject population, i.e., “administering a CCR5 inhibitor to a subject” (See 112(b) rejection supra) is extremely broad, and encompasses many mechanisms, cell types, and tissue types. In contrast to the breadth of the claims, the guidance and working examples provided in the Specification are far more limited. The Specification teaches that administration of 5P12-Rantes (SEQ ID NO: 9 + SEQ ID NO: 1 = SEQ ID NO: 70) in an experimental animal model of multiple sclerosis results in a decrease in cerebral inflammation (See Example 3 at pp. 78-79). Therefore, while the Specification provides adequate direction and guidance on how to treat or inhibit cerebral inflammation in a subject in need thereof, there is no guidance on how to inhibit or treat cerebral inflammation in an undefined subject population, or in a subject that is susceptible to a neuroinflammatory disorder that involves cerebral inflammation, or to even identify a subject that is susceptible to a neuroinflammatory disorder such that they could be treated. One skilled in the art would not know, with any level of predictability, that the administration of an undetermined amount of a CCR5 inhibitor would lead to the treatment of every possible subject encompassed by the scope of the claims.
15. Thus, in view of the breadth of the claims, the lack of direction and guidance, and the lack of working examples, the instant specification is not found to be enabling for the treating and/or preventing cerebral inflammation in the subject population encompassed by the scope of the claims. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention in its full scope.
Claim Rejections - 35 USC § 112, 1st Paragraph (Written Description)
16. Claims 1 and 6-20 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.
17. The U.S. Court of Appeals for the Federal Circuit recently reaffirmed, in an en banc decision, that the written description requirement for a genus may be satisfied either by (i) the disclosure of a representative number of species falling within the scope of the genus or (ii) structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus. Ariad Pharmaceuticals', Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350, 94 U.S.P.Q.2d 1161, 1171 (en banc) (Fed. Cir. 2010), citing Regents" of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69, 43 U.S.P.Q.2d 1398, 1406 (Fed. Cir. 1997).
18. The representative ways of satisfying the written description requirement as set out by the Federal Circuit in Ariad Pharmaceuticals comport with statements set out in the USPTO's Manual of Patent Examining Procedure (M.P.E.P.). In particular, the M.P.E.P. provides that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species of relevant identifying characteristics. M.P.E.P. § 2163, II, A, 3, (a), (ii).
19. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163.
20. The claims are drawn very broadly to a method of inhibiting cerebral inflammation in a subject, said method comprising administering a CCR5 inhibitor to a subject, wherein the CCR5 inhibitor is a polypeptide comprising an N-terminal portion and a C-terminal portion, wherein the N-terminal portion comprises the signature sequence QGP[P or L] and the C- terminal portion comprises an amino acid at least 70% identical to SEQ ID NO: 1 (See 112(b) rejection supra). The claims also recite wherein the signature sequence is QGP[P or L] [L or G or S or M] [M or D or S or Q or G]; wherein the signature sequence is QGP[P or L][L or G or S or M][M or D or S or Q or G]XX[Q or G or L or A or T or S]X, wherein X denotes any natural or modified amino acid; wherein the signature sequence is QGP[P or L]LM or QGPPG[D or S]; wherein the signature sequence is QGP[P or L][L or M][M or Q][A or W or G or Q or N]X[Q or G or L][S or V or T or G], wherein X denotes any natural or modified amino acid; wherein the signature sequence is QGPPLM[A or W][L or T or M][Q or G][S or V or T or G]; or wherein the signature sequence is QGPP[G or L][M or Q]XX[Q or S][S or V], wherein X denotes any natural or modified amino acid. Thus, the claims are drawn to a genus of molecules that are defined only by a partial structure, or by a limited structure and a required function in the claims utilizing them in the method.
21. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, while the Specification discloses a single 5P12-Rantes polypeptide (SEQ ID NO: 9 + SEQ ID NO: 1 = SEQ ID NO: 70) when administered in an experimental animal model of multiple sclerosis results in a decrease in cerebral inflammation (See Example 3 at pp. 78-79), it does not teach a commensurate number of the claimed polypeptides that are encompassed by the scope of the claims that also exhibit these activities. The distinguishing characteristics of the claimed genus are not described. The only adequately described species is the 5P12-Rantes polypeptide (SEQ ID NO: 9 + SEQ ID NO: 1 = SEQ ID NO: 70). Accordingly, the specification does not provide adequate written description of the claimed genus.
22. For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
A “patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”), see MPEP 2163.IIAii.
23. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
24. With the exception of the 5P12-Rantes polypeptide referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed proteins, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
25. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 102
26. 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 (i.e., changing from AIA to pre-AIA ) for the rejection 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.
27. 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.
28. Claim(s) 1 and 6-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hartley (WO 2008/012689; published 31 July 2008).
29. It is noted that the instantly claimed methods do not limit the patient population to which the treatment is administered (See 112(b) rejections supra). Hartley teaches methods of administering a fusion polypeptide of SEQ ID NO: 9--SEQ ID NO: 1 (i.e. present SEQ ID NO: 70/5P12-RANTES/5P12-CCL5S) to treat cancer (please refer to the entire specification particularly the abstract; pages 3-7, 10, 11, 17-22, 24-28; claims). Hartley also teaches present SEQ ID NOs: 2-15, 30-43, and 73-77 (please refer to the entire specification particularly pages 4-8, 24, 28; claims). Hartley teaches that the fusion polypeptides are selective for CCR5 over CCR1 and CCR3, inhibit a subset of intracellular signaling pathways, inhibit inflammatory effects of CCRS, and have a signaling response of 30% or less of the Emax elicited by PSC- RANTES when tested as a concentration of 300 nM in a calcium flux signaling assay (please refer to the entire specification particularly pages 2, 3, 9, 12, 13, 31, 32, 37, 38; Table 4). Therefore, the teachings of Hartley anticipate the presently claimed method since the claimed methods do not limit the patient population to which the treatment is administered.
Double Patenting
30. 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.
31. Claims 1 and 6-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. 8,686,111. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are drawn to administering a CCR5 inhibitor to a subject (i.e., any subject population). Both the present claims and the claims of the ‘111 Patent recite treating subjects with CCR5 inhibitors, including a fusion polypeptide comprising QGP[P or L] and SEQ ID NO: 1. The claims of the ‘111 Patent also recite wherein the signature sequence is SEQ ID NO: 9 (i.e., SEQ ID NO: 9 + SEQ ID NO: 1 = SEQ ID NO: 70). Therefore the claims are overlapping in scope.
32. Claims 1 and 6-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 9,328,153. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are drawn to administering a CCR5 inhibitor to a subject (i.e., any subject population). Both the present claims and the claims of the ‘153 Patent recite treating subjects with CCR5 inhibitors, including a fusion polypeptide comprising QGP[P or L] and SEQ ID NO: 1. The claims of the ‘111 Patent also recite wherein the signature sequence is SEQ ID NO: 9 (i.e., SEQ ID NO: 9 + SEQ ID NO: 1 = SEQ ID NO: 70). Therefore the claims are overlapping in scope.
Summary
33. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jon M. Lockard whose telephone number is (571) 272-2717. The examiner can normally be reached on Monday through Friday, 8:00 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached on (571) 272-2911. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JON M LOCKARD/
Examiner, Art Unit 1647
September 30, 2026
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