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 .
Response to Amendments and Arguments
2. Claims 1-11 and 16-18 are pending.
Claims 1-10 are withdrawn from consideration as being drawn to non-elected inventions and non-elected species.
Claims 11 and 16-18 has been amended.
Claims 11 and 16-18 are examined on the merits.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
3. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
4. Claims 11 and 16-18 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. THIS IS A NEW MATTER REJECTION. The claim(s) contain 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.
Applicant has amended the claims to recite treating leukemia or malignant lymphoma with the administration of the combination of a pharmaceutical composition with a polyclonal IgG antibody or functionally equivalent thereof produced by immunizing a mouse or rabbit with a polypeptide consisting of the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 12, wherein the said antibody specifically binds to an extracellular region of a melanocortin 2 receptor accessory protein (MRAP2). However, there is no support within the specification for this in vivo treatment with this particular therapeutic combination of therapeutic agents. The Examiner has reviewed the specification and does not note this experimental design.
Applicant is requested to point out where in the disclosure support can be found for this method of in vivo treatment with the recited agents. If Applicant is unable to indicate where in the specification by page, line, section and/or paragraph support or evidence can be found for the newly amended claims, Applicant should delete the new matter.
5. Claims 11 and 16-18 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant’s claims read on treating leukemia or malignant lymphoma with the administration of a polyclonal IgG antibody or functionally equivalent thereof produced by immunizing a mouse or rabbit with a polypeptide consisting of the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 12 in combination with a pharmaceutical composition. However, the specification does not evidence in vivo treatment of any cancer cells, cancerous tissue and in particular, leukemia or malignant lymphoma.
However, Applicant’s specification does not evidence the treatment as described in the claims, see the entire disclosure.
It appears that undue experimentation would be required of one skilled in the art to practice the instant claimed invention. See Ex parte Forman, 230 USPQ 546 BPAI, 1986. Granted the Office does not require that experiments under the scope of the claims produce positive and astonishing results, the experiments must be within the scope of the Forman factors (see Ex parte Forman, 230 USPQ 546, BPAI, 1986). There would also need to be some valid amount of direction or guidance, as well as presence or absence of working examples presented in the specification that would enable one skilled in the art to perform the method as presented in the recited claims.
In absence of guidance and/or working examples, one skilled in the art would not reasonably conclude that the therapeutic combination of a polyclonal IgG antibody and pharmaceutical composition could be administered to a patient effective to treat leukemia or malignant lymphoma and the specification has not taught effective therapeutics directed to the said cancers.
It is well known in the art of cancer treatment that tumors of differing cell types respond differently to a given therapeutic approach, and that a treatment modality that is effective against of a tumor of one given cell type would not necessarily be expected to be effective against tumors of differing histological origin. Cancers differ in histopathobiologies, as well as etiologic origin. Those of skill in the art do not expect neoplasms of all cell types to respond in a similar fashion to the administration of a given class of molecules. And more specifically, it is also art known while leukemia and lymphoma are both blood cancers they are different types that originate from distinct body sites, affect different organ and cells, as well as treatment is dependent upon the stage of the cancer. Therefore, one of skill in the art would conclude that a prophylactic regimen would not only be unpredictable. There are no reasons why one of skill in the art would expect the claimed method would be capable of treating different cancer types given the unpredictable nature of treating cancer. The specification fails to provide sufficient guidance to enable one of ordinary skill in the art to use these polyclonal IgG antibodies in a manner reasonably correlated with the broad scope of the claimed method.
Thus, undue experimentation would be required to implement the instantly claimed method for the treatment of leukemia or malignant lymphoma with the administration of a polyclonal IgG antibody or functionally equivalent thereof produced by immunizing a mouse or rabbit with a polypeptide consisting of the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 12 with a pharmaceutical composition. The scope of the claims must bear a reasonable correlation with the scope of enablement. One skilled in the art would be forced into undue experimentation in order to practice the broadly claimed invention.
6. The rejection of claims 11 and 16-18 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 is maintained.
Applicant asserts the amendment to claim 11, “…has now limited the antibody…to an “IgG antibody”, which “…has a particular type of antibody structure, the limitation should contribute to the structural definition of the antibodies.”, see Remarks submitted July 23, 2025, page 6, 1st paragraph (para.).
Thereafter, Applicant notes the alleged attributes of melanocortin 2 receptor accessory protein 2 (MRAP) and teachings within the specification, namely Example 3 (spanning pages 43-47) and Example 4 (spanning pages 47 and 48), see Remarks, page 6 and 7. Applicant states “Example 3 establishes that MRAP2 protein is expressed on the surface of leukemia cells and malignant lymphoma cells by detecting MRAP2 protein with polyclonal antibodies against the N-terminal portion (SEQ ID NO: 10) or C-terminal portion (SEQ ID NO: 12) of the MRAP2 protein, which indicates that the N-terminal portion (SEQ ID NO: 10) and C-terminal portion (SEQ ID NO: 12) of MRAP2 protein are present on the surface of leukemia cells and malignant lymphoma cells. Here, it is clear that the polyclonal antibody is produced by immunizing a mouse or a rabbit with a polypeptide consisting of the amino acid sequence of SEQ ID NO: 10 or 12, which is recited in claim 11.”, see para. bridging pages 6 and 7. And “Example 4 titled “Antitumor effects (ADCC activity) of polyclonal antibody against MRAP2 to cancer cells,” showing that both of (i) the polyclonal antibody against an extracellular N-terminal portion of MRAP2 protein (SEQ ID NO: 10), and (ii) the polyclonal antibody against an extracellular C-terminal portion of MRAP2 protein (SEQ ID NO: 12), exhibited ADCC activity as antitumor effects against leukemia cells (cell line K562) and malignant lymphoma cells (cell line Namalwa). See paragraphs [0133]- [0135]. [Claim 11 recites leukemia or malignant lymphoma.]”, see page 7, 2nd para.
Applicant’s arguments, points of view and disclosures within the specification have been carefully considered but fail to persuade.
The amendment to claims does not further Applicant’s support, nor evidence they have written description of the polyclonal IgG antibodies and functional equivalent thereof cited within the newly amended claim 11. The polyclonal IgG antibody has the functional element denoting it specifically binds an extracellular region of MRAP2 consisting of either amino acid sequence shown in SEQ ID NO: 10 or SEQ ID NO: 12 and produced with the immunization of a mouse or rabbit. Applicant continues to not meet the written description requirement because they have not provided evidence of the antibody and its functional equivalents are in possession of the Applicant, but rather how to make them and claims and specification are still absent of information showing a structure/function correlation and any number of species representative of the breadth of the genus.
The Board decision mailed January 17, 2024 informed all parties, “Appellant contends that its Specification makes obvious the preparation of antibodies within the scope of its claimed invention. We are not persuaded. “One shows that one is ‘in possession’ of the invention by describing the invention, with all its claimed limitations, not that which makes it obvious. One does that by such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention.” Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (citation omitted).
The purpose of the “written description” requirement is broader
than to merely explain how to “make and use”; the applicant
must also 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.
Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991).”, see Board Decision mailed January 17, 2024, pages 7 and 8.
The Board further stated “[k]nowledge of a target antigen is not sufficient to provide written description for the entire class of antibodies that bind to that antigen.
[T]he “newly characterized antigen” test flouts basic legal principles of the
written description requirement. Section 112 requires a “written description
of the invention.” But this test allows patentees to claim antibodies by
describing something that is not the invention, i.e., the antigen. The test hus
contradicts the statutory “quid pro quo” of the patent system.
Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378-79 (Fed. Cir. 2017);6 see Juno Therapeutics, Inc., v. Kite Pharma, Inc., 10 F.4th 1330, 1337 (Fed. Cir. 2021)”, see Board Decision mailed January 17, 2024, paragraph bridging pages 9 and 10.
Applicant has not met the requirement because they continually do not show the correlation between function and structure, nor a number of species either disclosed in the Specification or known in the art that are representative of the breadth of the genus. Applicant repeatedly points out their Examples, however none of these Examples are representative of the full breadth of MRAP2 polyclonal IgG antibodies and functional equivalents thereof.
The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of the polyclonal IgG antibodies that bind SEQ ID NO: 10 or SEQ ID NO: 12. The ability to make polyclonal antibodies essential to the claimed methods does not place the skilled artisan in possession of the relevant identifying characteristics of a genus of antibodies commensurate in scope with the claimed invention. Notwithstanding, Applicant has essentially submitted “…it is impossible and impractical to determine CDR sequences of a polyclonal antibody and specify the polyclonal antibody by the CDR sequences. It is unreasonable to require a patent applicant to specify a polyclonal antibody by its CDR sequences, considering the impossible and impractical circumstances,”, see Remarks, page 7, 4th para.
For the reasons of record and cited herein the rejection is maintained.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention reads broadly on treating a MRAP2 expressing cancer with the administration of a polyclonal IgG antibody or functionally equivalent thereof in combination with a pharmaceutical composition, wherein said polyclonal antibody specifically bind a polypeptide of the extracellular region of a MRAP2 consisting of the amino acid sequence shown in SEQ ID NO: 10 or SEQ ID NO: 12, wherein the said antibody has an ADCC activity against a cancer cell and the said MRAP2 expressing cancer is leukemia or malignant lymphoma.
The written description in this instant case does not sufficiently set forth a polyclonal IgG antibody and functional equivalent thereof that bind SEQ ID NO: 10, nor SEQ ID NO: 12. This plethora of polyclonal IgG antibodies and functional equivalents thereof have not been fully defined and characterized.
Vas-Cath Inc. V. Mahurkar, 19 U5PQ2d 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).
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 115). The skilled artisan cannot envision the detailed structure of the encompassed polypeptides 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 a reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 U5PQ 2d 1601 at 1606 (CAFC1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts. 18 U5PQ2d 1016.
Furthermore, In The Reagents of the University of California v. Eli Lilly (43 U5PQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of DNA molecules, usually defined by a nucleotide sequence, falling within the scope of the claimed genus. At section B(l), the court states that "An adequate written description of a DNA...'requires a precise definition, such as by structure, formula, chemical name, or physical properties', not a mere wish or plan for obtaining the claimed chemical invention".
At the time the application was filed Applicants does not have possession of the breadth of polyclonal IgG antibodies and functional equivalents thereof. The specification does not evidence the possession of all these said antibodies and functional equivalents thereof that are undefined and uncharacterized falling within the potentially large genus to establish possession. There is insufficient to support the generic claims as provided by Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See
https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 U5PQ2d 1398.
The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Conclusion
7. 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
8. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
November 3, 2025
/Alana Harris Dent/Primary Examiner, Art Unit 1643