Patent Application 17957302 - AXL-SPECIFIC ANTIBODY-DRUG CONJUGATES FOR CANCER

Title: AXL-SPECIFIC ANTIBODY-DRUG CONJUGATES FOR CANCER TREATMENT

Application Information

Invention Title: AXL-SPECIFIC ANTIBODY-DRUG CONJUGATES FOR CANCER TREATMENT
Application Number: 17957302
Submission Date: 2025-05-14T00:00:00.000Z
Effective Filing Date: 2022-09-30T00:00:00.000Z
Filing Date: 2022-09-30T00:00:00.000Z
National Class: 424
National Sub-Class: 181100
Examiner Employee Number: 73645
Art Unit: 1646
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 1

Cited Patents

No patents were cited in this rejection.

Office Action Text

DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .

Election/Restrictions
Applicant’s election in the reply filed on 4/29/2025 is acknowledged:

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An ADC with the sixth antibody, Ab613, is included in the species election, consistent with the election in parent application 16/069395.
Claims 1-3, 10, 11, 13, 14, 25, 30, 32, 33, 35-38, 41, 44, 47-50, 52, 54, 57-60, 64, 66-68, and 78 read on the elected species and are treated on the merits, below. Claims 16, 21, 24 are withdrawn from consideration as exclusively covering non-elected species.

Claim Rejections - 35 USC § 112
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.

Claims 1-3, 10, 11, 13, 14, 25, 30, 32, 33, 35-38, 41, 44, 47-50, 52, 54, 57-60, 64, 66-68, and 78 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.
The rejected claims cover methods of using antibody-drug conjugates (ADC’s) and inhibitors of the MAPK pathway.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of ADC’s and inhibitors, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[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.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 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 the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "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."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify particular ADC’s and inhibitors encompassed by the claims. The specification does not provide adequate written description of the claimed genus of ADC’s and inhibitors. Specifically, Applicant fails to disclose any other ADC’s and inhibitors, besides those covered by the formulas in the specification, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of ADC’s and inhibitors.
With regard to the functional definition of antibody-drug conjugates that binds human AXL or inhibitors of MAPK pathway, 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) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an infinite number of conjugates and compounds to see if the conjugates and compounds can perform the required functions, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited antibody-drug conjugates (ADC’s) that bind AXL and inhibitors of the MAPK pathway.

Claims 1-3, 10, 11, 13, 14, 25, 30, 32, 33, 35-38, 41, 44, 47-50, 54, 60, 64, 66 and 67 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.
Here, a genus of antibodies that can bind to human AXL, or functional fragments thereof, or any % homology to fragments thereof, lack written description because the recited functional definition of the anti-axl antibody does not describe the claimed invention.
Here, the genus of antibodies cannot be adequately described by functional characteristics of preferential binding, even where there is disclosed or known correlations between structure and function.
The Examiner recognizes that the target, AXL, may be fully characterized. Previously, disclosing a bonding target, such as ofCS satisfies the written description requirement for a claim to an antibody or protein that binds the target. The Federal Circuit's decisions in Enzo Biochem v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002) and Noelle v. Lederman, 355 F. 3d 1341 (Fed. Cir. 2004) which purportedly set forth what has been called the "newly characterized antigen" test. Also, the PTO's Written Description Training Materials Revision dated March 25, 2008, provide an example (Example 13) embodying the test set forth in Enzo and Noelle.
However, reliance on Enzo and Noelle is misplaced. While the court in Noelle did discuss what is referred to as the "newly characterized antigen" test, the Federal Circuit has recently rejected such a test. Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378-79 (Fed. Cir. 2017). At issue in Amgen was the district court's jury instruction which read:
In the case of a claim to antibodies, the correlation between structure and function may also be satisfied by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that the production of antibodies against such an antigen was conventional and routine.
Id. at 1376. The Federal Circuit concluded that the instruction was "not legally sound and [was] not based on any binding precedent." Id. In reaching its conclusion the Federal Circuit reviewed the cases which purported to set forth the newly characterized antigen test including Noelle. Id. at 1376-77. The court concluded that in each of the prior cases the reference to the newly characterized antigen test was dicta and not binding precedent. Id.
The Federal Circuit went on to find that the newly characterized antigen test ran afoul of the Federal Circuit's precedent in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane). Id. at 1378. The court noted that the focus of the inquiry is whether the written description contains enough information about the claimed products. Id. The court held that describing the antigens, which was not the claimed invention, did not satisfy the written description requirement when (“it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid... does not tell you anything at all about the structure of the antibody [emphasis applied]"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In a memo issued in February 2018, USPTO, Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, Feb. 22, 2018 (available at https://www.usnto.gov/sites/defauH/files/documents/amgen 22feb2018.pdf) the PTO issued a clarification regarding the law of written description as it applies to antibodies stating:
In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
The Memo goes on to state that
"Examples in the 2008 Written Description Training Materials Are Outdated." and should NOT be relied upon as reflecting the current state of the law. Id. at 2. The Memo explains that
USPTO personnel should continue to follow the guidance in the MPEP regarding written description (see, e.g., MPEP 2161.01 and 2163 ), except insofar as MPEP 2163 indicates that disclosure of a fully characterized antigen may provide written descriptive support of an antibody to that antigen.
Id.
The instant claims present the same deficiency as the claims in Amgen where there is no evidence that knowledge of the chemical structure of AXLgives the required kind of structure-identifying information about the corresponding peptides that it binds. As in Amgen, the instant claims attempt to describe an anti-AXL ADC by describing the target to which the peptides bind. Moreover, there is nothing else in the disclosure that describes the peptides as required by the test set forth in Ariad.
Moreover, regard to the functional definition the ADC, 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) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an inordinate number of peptides to see if the compounds can perform the required binding. In this connection, the specification contains no structural or specific functional characteristics of those peptides which bind AXL, besides those peptides with amino acid sequences corresponding to the disclosed SEQ ID NO’s, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
Accordingly, the specification lacks adequate written description for the recited antibodies that bind human AXL.

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.

Claims 16, 21 and 24 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.

It is unclear what analogs or derivates Applicant intends to cover in the rejected claims.

Claim Rejections - 35 USC § 103
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, 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.

Claims 1-3, 10, 11, 13, 14, 25, 30, 32, 33, 35-38, 41, 44, 47-50, 60, 64, 66 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015193430 (WO 430) in view of Wan et al., Cell, Vol. 116, 855–867, March 19, 2004 (Wan).

WO 430 describes anti AXL antibodies and ADC’s thereof to be used for treating cancers such as melanomas in combination with other chemotherapeutics, such as sorafenib (page 51, § 1, page 52, § 1). WO 430 describes the use of anti-AXL antibody drug conjugates (ADC) to treat cancer including melanomas.

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See page 28
The anti-AXL antibodies were conjugated to MMAE. Combination with agents such as sorafenib is proposed, see pages 51+. In particular, the use of MAP kinase inhibitors or the treatment of melanomas with specific mutations/resistances represent some of several straightforward possibilities from which the skilled person would select, in accordance with circumstances, without the exercise of inventive skill.
With regard to BRAF mutations, there is no particular effect associated with the difference since there is no evidence in the application relating to the treatment of melanomas with the specific mutations or resistances i.e. vemurafenib or dabrafenib etc. Neither there is any evidence that there is a particular effect associated with the difference in the sequences of the antibodies.
The claims require an inhibitor of the MAPK pathway (e.g., B-RAF (BRAF) inhibitor, a MEK inhibitor, or an ERK inhibitor). it is for that proposition the examiner joins Wan et al., Cell, Vol. 116, 855–867, March 19, 2004, which teaches that sorafenib (i.e., BAY43-9006), as taught by WO 430 is a mutant V600E mutant B-Raf inhibitor. Specifically, Wan teaches that BAY43-9006 (Sorafenib, Nexavar) is a V600E mutant B-Raf and C-Raf inhibitor approved by the FDA for the treatment of primary liver and kidney cancer. Bay43-9006 disables the B-Raf kinase domain by locking the enzyme in its inactive form. The inhibitor accomplishes this by blocking the ATP binding pocket through high-affinity for the kinase domain. It then binds key activation loop and DFG motif residues to stop the movement of the activation loop and DFG motif to the active conformation. Finally, a trifluoromethyl phenyl moiety sterically blocks the DFG motif and activation loop active conformation site, making it impossible for the kinase domain to shift conformation to become active. For example:

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In this manner, the applied references provide a reasonable expectation that a combination of anti-AXL ADC’s and B-RAF inhibitors can treat cancer. Specifically, the difference between WO 430 and the claimed inventions is that WO 430 does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, based on the above, WO 430 teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).

Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646