DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 3/11/26, are acknowledged.
Claims 6, 15, 1934, 36, 39, 42-44, 47 have been amended.
Claims 6, 9, 12, 14-16, 19, 25, 28, 30-34, 36-37, 39, 42-45, 47, 49, 52, and 55 are pending and are under examination.
In view of Applicant’s claim amendments, only the following rejections remain. The enablement rejection has been modified to the extent necessary to address Applicant’s claim amendments.
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.
Claims 34, 36-37, 39, 42-45, 47, 49, 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an isolated antibody against human gremlin1 or an antigen binding fragment therefore comprising a VH region and a VL region, wherein the VH HCDR1-3 and the VL LCDR1-3 comprise the CDRs as defined in a)-h) of claim 6;
does not reasonably provide enablement for:
A method of treating a GREM1-related disease or condition comprising administering to the subject a therapeutically effective amount of said antibody or antigen binding fragment thereof.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The claims encompass methods of treating GREM1-related disease or condition, including, for example, fibrosis The state of the art is such that treating diseases with gremlin-1 antibodies is highly unpredictable. For example, gremlin-1 antibodies are not effective in treating liver fibrosis and do not reduce liver inflammation or liver fibrosis, even when the antibodies block binding of gremlin to BMPs (see Horn, 2024). Thus, treating the diseases encompassed by the instant claims, would be highly unpredictable.
Thus, based on the breadth of the claims and the unpredictability of the art, the instant specification must provide a sufficient and enabling disclosure, commensurate in scope with the instant claims. The instant specification discloses gremlin1 antibodies having defined VH/VL pairs that were produced by immunizing mice with a human gremlin1 protein. The instant specification discloses that the antibodies can decrease tumor volume and decrease tumor growth in a treated subject, however, no guidance or examples are provided regarding treating the other Gremlin1 diseases, as encompassed by the present claims. Thus, based on the breadth of the claims, the unpredictability of the art, and the lack of guidance provided by the instant specification, it would require undue experimentation to make and use the antibodies and antibody fragments as broadly claimed.
Applicant argues that the amendment to recite the specific diseases overcomes the rejection.
However, the list of specific diseases recited in claim 34 includes fibrotic diseases (see also claim 44 which recites that the fibrotic disease is liver). As noted above, the state of the art is such that gremlin-1 antibodies are not effective in treating liver fibrosis and do not reduce liver inflammation or liver fibrosis, and liver fibrosis is unamenable to therapeutic targeting of Gremlin-1 (see Horn). The instant specification does not disclose any examples or guidance for treating any fibrotic disease or any other disease other than cancer. It is noted that even though dependent claims recite features regarding cancer, they are nevertheless rejected as they depend from claim 34. For example, claim 36 defines the features of the cancer, but dos not limit the claims to treating cancer (claim 36, if incorporated into claim 34, would encompass treating fibrosis or cancer, wherein the cancer is GREM-1 expressing). Claim 37 recites that the subject is “identified as having a GREM-1 expressing cancer” but would still encompass treating a fibrotic disease (or other GREM-1 conditions) in a subject with a GREM-1 expressing cancer, for example. Amendment to limit claim 34 to treating cancer would be remedial.
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.
Claim 6, 9, 12, 14-16, 19, 25, 28, 30-34, 36-37, 39, 42-45, 47, 49, 52, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 7-10, 12-13, 15, 17, 19-20, 23, 25, 28, 31, 37, 40, 43, 47-49, 56, 58, 61 of copending Application No. 18/549,928 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘928 application claims a method of treating a GREM-1 expressing cancer or fibrotic disease comprising administering to a subject a GREM1 antagonist, and claims that the antagonist is an antibody comprising the same CDRs as recited in a)-d), or the same VH and VL of the instant claims (i.e. the claims of the ‘928 application cover the same antibodies of the instant claims). The ‘928 application claims that the antibody is humanized or IgG1, or bispecific, wherein the bispecific antibody also targets PD-`, or administering a second therapeutic agent such as an androgen axis inhibitor degarelix. The ‘928 application claims that the cancer is triple negative breast cancer, or esophageal cancer. Although not specifically claimed in the ‘928 application, it would be obvious to produce the antibody recombinantly by expressing it in a host cell from a polynucleotide as is well known in the art. Furthermore, it would be obvious to further test the treated subjects for GREM1 antagonist activity (i.e. to test whether a sample from the subject has reduced GREM1 using the antagonist antibody) in order to monitor the efficacy of the treatment method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s statement that the rejection be held in abeyance until the time of allowance is acknowledged.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights